Abstract: As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.

Abstract: Pneumonia associated with the 2019 novel coronavirus (2019-nCoV) is continuously and rapidly circulating at present. No effective antiviral treatment has been verified thus far. We report here the clinical characteristics and therapeutic procedure for four patients with mild or severe 2019-nCoV pneumonia admitted to Shanghai Public Health Clinical Center. All the patients were given antiviral treatment including lopinavir/ritonavir (Kaletra®), arbidol, and Shufeng Jiedu Capsule (SFJDC, a traditional Chinese medicine) and other necessary support care. After treatment, three patients gained significant improvement in pneumonia associated symptoms, two of whom were confirmed 2019-nCoV negative and discharged, and one of whom was virus negative at the first test. The remaining patient with severe pneumonia had shown signs of improvement by the cutoff date for data collection. Results obtained in the current study may provide clues for treatment of 2019-nCoV pneumonia. The efficacy of antiviral treatment including lopinavir/ritonavir, arbidol, and SFJDC warrants further verification in future study.

Abstract: Rapidly sharing scientific information is an effective way to reduce public panic about COVID-19, and doing so is the key to providing real-time guidance to epidemiologists working to contain the outbreak, clinicians managing patients, and modelers helping to understand future developments and the possible effectiveness of various interventions. This issue has rapidly reviewed and published articles describing COVID-19, including the drug treatment options for SARS-CoV-2, its clinical characteristics, and therapies involving a combination of Chinese and Western medicine, the efficacy of chloroquine phosphate in the treatment of COVID-19 associated pneumonia according to clinical studies, and reflections on the system of reserve medical supplies for public health emergencies. As an academic journal, we will continue to quickly and transparently share data with frontline healthcare workers who need to know the epidemiological and clinical features of COVID-19.

Abstract: On December 31, 2019, the Wuhan Municipal Health Commission announced an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), China is now at a critical period in the control of the epidemic. The Chinese Government has been taking a series of rapid, comprehensive, and effective prevention and control measures. As the pandemic has developed, a fact has become apparent: there is a serious dearth of emergency medical supplies, and especially an extreme shortage of personal protective equipment such as masks and medical protective clothing. This is one of the major factors affecting the progress of epidemic prevention and control. Although China has made great efforts to strengthen the ability to quickly respond to public health emergencies since the SARS outbreak in 2003 and it has clarified requirements for emergency supplies through legislation, the emergency reserve supplies program has not been effectively implemented, and there are also deficiencies in the types, quantity, and availability of emergency medical supplies. A sound system of emergency reserve supplies is crucial to the management of public health emergencies. Based on international experiences with pandemic control, the world should emphasize improving the system of emergency reserve medical supplies in the process of establishing and improving public health emergency response systems, and it should promote the establishment of international cooperative programs to jointly deal with public health emergencies of international concern in the future.

Abstract: To investigate the characteristic of coagulation function in 303 patients with Coronavirus disease 2019 (COVID-19), we evaluated the correlation between coagulation function and disease status. We retrospectively analyzed 303 patients diagnosed with COVID-19 and evaluated the clinical data of 240 patients who were discharged. The coagulation function of the two groups (mild and severe) was compared. Compared with the mild group, majority of patients in the severe group were male (76.9% vs. 49.8%) and elderly (median age 65 vs. 50), and the proportion with chronic underlying diseases was higher (73.1% vs. 36.1%). There were 209 abnormalities (69.0%) of coagulation parameters in 303 patients admitted to hospital. Comparison of various indexes of coagulation function between the two groups in admission, the proportion of abnormal coagulation indicators in the severe group was higher than that in the mild group (100% vs. 66.1%). The median coagulation parameters in the severe group were higher than those in the mild group: international normalized ratio (1.04 vs. 1.01), prothrombin time (13.8 vs. 13.4) seconds, activated partial thromboplastin time (43.2 vs. 39.2) seconds, fibrinogen (4.74 vs. 4.33) g/L, fibrinogen degradation products (2.61 vs. 0.99) µg/mL, and D-dimer (1.04 vs. 0.43) µg/mL, the differences were statistically significant (p < 0.05). Coagulation dysfunction is common in patients with COVID-19, especially fibrinogen and D-dimer elevation, and the degree of elevation is related to the severity of the disease. As the disease recovers, fibrinogen and activated partial thromboplastin time also return to normal.

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that has developed in late 2019 and 2020 is a serious threat to human health. With no vaccines or drugs approved for prevention and treatment until now, all efforts at drug design and/or clinical trials of already approved drugs are worthy and creditable. Using structure-based drug selection for identification of SARS-CoV-2 protease inhibitors, old drugs such as macrolides (MAC) were predicted to be effective for COVID-19. Lately, the anti-viral effects of macrolides have attracted considerable attention. Very recently, hydroxychloroquine in combination with azithromycin treatment was reported to be effective for COVID-19. We believe that treatments with macrolides alone or in combination with other drugs are promising and open the possibility of an international strategy to fight this emerging viral infection.

Abstract: Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.

Abstract: During the COVID-19 outbreak, China made great progress in controlling the epidemic, and the number of confirmed and suspected cases continues to decrease thanks to the various efforts employed. Mobile field hospitals have played a huge role in the centralized management of patients and they have effectively reduced transmission. This article describes some of our experiences operating mobile field hospitals in order to provide a reference and to better inform countries that are dealing with this crisis.

Abstract: In late March and early April 2020, the antimalarial drug, chloroquine, has been approved as an emergency treatment for the coronavirus disease 2019 (COVID-19) in the United States and in Europe. Although infrequent, neuropsychiatric symptoms have been reported in patients who received chloroquine for the treatment of malaria or autoimmune diseases. In this study, aiming to investigate these adverse events (AEs) using a large self-reporting database, we conducted a disproportionality analysis for the detection of neuropsychiatric AE signals associated with the use of chloroquine (or hydroxychloroquine), reported to FDA Adverse Event Reporting System (FAERS) database between the fourth quarter of 2012 and the fourth quarter of 2019. We included 2,389,474 AE cases, among which 520 cases developed neuropsychiatric AE following the use of chloroquine. Adjusted reporting odds ratio (ROR) for the development of each of the neuropsychiatric AEs following the use of chloroquine was calculated using a multilevel model: exposure to chloroquine was associated with a statistically significant high reporting of amnesia, delirium, hallucinations, depression, and loss of consciousness, (lower 95% confidence interval of the adjusted ROR > 1), although the degree of increase in their ROR was limited. There was no statistically significant high reporting of any other neuropsychiatric AE, including suicide, psychosis, confusion, and agitation. Current pharmacovigilance study results did not suggest any potential link between the use of chloroquine and an increased risk of suicide, psychosis, confusion, and agitation, which would be informative during the emergency use of chloroquine for the treatment of COVID-19.

Abstract: NLRP3 inflammasome plays an essential role in innate immunity, yet the activation mechanism of NLRP3 inflammasome is not clear. In human or animal models, inappropriate NLRP3 inflammasome activation is implicated in many NLRP3-related diseases, such as tumors, inflammatory diseases and autoimmune diseases. Until now, a great number of inhibitors have been used to disturb the related signaling pathways, such as IL-1β blockade, IL-18 blockade and caspase-1 inhibitors. Unfortunately, most of these inhibitors just disturb the signaling pathways after the activation of NLRP3 inflammasome. Inhibitors that directly regulate NLRP3 to abolish the inflammation response may be more effective. NEK7 is a multifunctional kinase affecting centrosome duplication, mitochondrial regulation, intracellular protein transport, DNA repair and mitotic spindle assembly. Researchers have made significant observations on the regulation of gene transcription or protein expression of the NLRP3 inflammasome signaling pathway by NEK7. Those signaling pathways include ROS signaling, potassium efflux, lysosomal destabilization, and NF-κB signaling. Furthermore, NEK7 has been proved to be involved in many NLRP3-related diseases in humans or in animal models. Inhibitors focused on NEK7 may regulate NLRP3 to abolish the inflammation response and NEK7 may be a potential therapeutic target for NLRP3-related diseases.

Abstract: This study aimed to determine the clinical significance of Krebs von den Lungen-6 (KL-6) in patients with COVID-19, so as to find a marker with high sensitivity, specificity and easy detection to evaluate the lung injury and inflammation of COVID-19 Sixty-three COVID-19 patients and 43 non-COVID-19 patients with similar clinical phenotypes and/or imaging findings were enrolled to test the levels of KL-6 using chemiluminescent immunoassay In addition, the blood gas, imaging and lymphocyte factors tests were collected from all participants The data was finally analyzed using multivariate statistical analysis The results showed KL-6 levels in COVID-19 patients were higher than those in non-COVID-19 patients (P < 0001) Moreover, the KL-6 levels in severe and critically severe patients were significantly upregulated compared with patients with mild and common type (P < 005) Meanwhile, the imaging evaluation showed a significant correlation between KL-6 and pulmonary lesion area (P < 005) KL-6 was also found to be significantly correlated with oxygenation index and oxygen partial pressure difference of alveolar artery (PA-aDO2) (Both P < 001) In conclusion, KL-6 could be an indicator to evaluate the progression of COVID-19, which is parallel to the level of lung injury and inflammation in patients Moreover, it can also reflect the pulmonary ventilation function

Abstract: A number of inflammation indicators based on C-reactive protein (CRP) and albumin have been widely used to predict the prognosis in several types of tumors, but their functions in gallbladder cancer (GBC) have rarely been explored. The aim of our study is to evaluate and compare the prognostic values of the C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS) and high-sensitivity modified Glasgow prognostic score (HS-mGPS) in patients with GBC. 144 GBC patients who received curative surgery in our hospital from January 2010 to May 2017 were enrolled in this research. The Kaplan-Meier analysis showed that the median OS of the patients in the high CAR group was significantly shorter than the patients in the low group (p < 0.001), and higher scores of GPS, mGPS and HS-mGPS were also associated with decreased OS, respectively. However, according to the Receiver Operating Characteristic (ROC) curve, the CAR was superior to the other prognostic scores in determining the prognosis for the GBC patients. In the multivariate analysis, CAR was verified as an independent risk factor for poor prognosis, together with tumor differentiation, T stage and postoperative complications. All in all, compared to the other three CRP-albumin-related prognostic predictors, CRA is a better indicator in predicting poor long-term outcomes in GBC patients after radical surgery.

Abstract: Fifth Generation (5G) mobile communications technology became available in Japan as of the end of March 2020. The Ministry of Internal Affairs and Communications (MIC) is proceeding with a plan to use 5G for a doctor-to-doctor remote diagnosis system. This remote diagnosis offers patients the benefit of receiving advanced medical care without having to travel long distances. The provision of a remote diagnosis will provide elderly patients in rural areas with an earlier diagnosis without burdening patients in Japan where the aging population and the uneven distribution of doctors are increasing. However, the system will increase the burden on specialists by expanding the doctor's catchment area. As a solution to that problem, deep learning-based artificial intelligence (AI) is expected to reduce the burden on doctors. In order to realize 5G- and AI-based real-time diagnostic support, diagnostic imaging using AI and an AI model that provides instructions are required. This is because ultrasonography and endoscopy, which can be used for remote diagnosis, do not acquire data on fixed areas like a CT or MRI scan. The AI model needs to instruct the doctor at the patient's home in order to collect appropriate information in accordance with the patient's symptoms and status. In order to build an interactive AI model, the interactions between doctors who are making a remote diagnosis should be recorded as training data and a 5G-based remote diagnosis system should be created. A remote diagnostic support system incorporating 5G and interactive diagnostic imaging incorporating AI will result in a system that places less of a burden on patients and doctors.

Abstract: China is in a stage of rapid aging of its population, and its old-age dependency ratio has been increasing for decades. The acceleration of aging of the population and the increasing old-age dependency ratio will significantly increase the pressure on social security and public services, highlight the need for the effective supply of labor, and weaken the demographic dividend, which will continue to affect social vitality, the power to innovate, and potential economic growth rates. Promoting social engagement has been widely recognized as an effective strategy to address these challenges. Such an approach not only promotes the development of social productivity, but it also alleviates the social burden. Actively promoting the social engagement of the elderly is an important task in gerontology in China. Although the development of social engagement of the elderly is on the rise, the infrastructure and institutions to provide social engagement need to be enhanced. Improving social engagement in China is not just the responsibility of older adults themselves but also of the country and society as a whole. In the future, the entire society will fully understand the special role of older adults and increase their value through social engagement to achieve active and healthy aging in China.

Abstract: Circular RNAs (circRNAs) are non-coding RNAs molecules consisting of a covalently closed continuous loop which have no 5'-3' polarity and contain no polyA tail. Accumulating evidence demonstrates that circRNAs are involved in the initiation and progression of human malignancies. In this study, we explored the expression profile and regulatory role of circ-baculoviral IAP repeat-containing 6 (circ-BIRC6), a circular RNA, in malignant behaviors in non-small cell lung cancer (NSCLC). Expression levels of circ-BIRC6 and miR-4491 were examined in NSCLC patient samples and cell lines using quantitative real time PCR (qRT-PCR). In vitro roles of circ-BIRC6 knockdown on cell viability, colony formation, and apoptosis were assessed using the CCK-8, colony formation assay, and flow cytometry, respectively. The interactions between circ-BIRC6 and miR-449 were assessed using luciferase reporter and qRT-PCR assays. The in vivo role of circ-BIRC6 knockdown on tumor growth and apoptosis was evaluated in a xenograft mouse model of NSCLC. We found that expression levels of circ-BIRC6 in NSCLC patient samples and cell lines were elevated. Small interfering RNA (siRNA)-mediated circ-BIRC6 knockdown suppressed cell proliferation, colony formation, migration and invasion, and promoted apoptosis in NCI-H460 and A549 cells. In addition, miR-4491 was identified as a tumor-suppressor miRNA in NSCLC and circ-BIRC6 functions as a molecular sponge for miR-4491. Furthermore, circ-BIRC6 knockdown suppressed Wnt2B/β-catenin pathway. In vivo assay showed that depletion of circ-BIRC6 suppressed tumor growth, enhanced apoptosis, and decreased miR-4491 levels in a mouse xenograft model. These findings demonstrate that circ-BIRC6 functions as a critical regulator of proliferation and apoptosis via binding to and negatively regulating miR-4491, suggesting that circ-BIRC6 might be a potential target for treatment of NSCLC.

Abstract: Glioblastoma is one of the most difficult cancers to treat with a 5-year overall survival rate less than 5%. Temozolomide (TMZ) is an effective drug for prolonging the overall survival time of patients, while drug-resistance is an important clinical problem at present. Pennogenin-3-α-L-rhamnopyranosyl-(1→4)-[α-Lrhamno-pyranosyl-(1→2)]- β-D-glucopyranoside (N45), a steroidal saponin, was isolated from the rhizomes of Paris vietnamensis (Takht.), which is used as a Traditional Chinese Medicine and has been reported to possess preclinical anticancer efficacy in various cancer types. However, the mechanism of the inhibition of N45 on glioblastoma cells and its possible application in the treatment of chemotherapy-resistant glioblastoma cells are still unknown. In this study, we use cellular methodological experiments including cell counting kit-8 (CCK-8) assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining assay, flow cytometry assay, transmission electron microscopy (TEM) and Western blot. The results show that N45 significantly suppresses the proliferation of glioblastoma cells and TMZ-resistant glioblastoma cells (U87R) by inducing mitochondrial apoptosis through reactive oxygen species (ROS)/phosphoinositide 3-kinase (PI3K)/Akt signal pathway, and the N-acetyl-L-cysteine (NAC) combined with N45 effectively reduced N45-mediated apoptosis and reversed the inhibition of PI3K/Akt signal pathway. In addition, N45 decreased the drug-resistance by down-regulation of nuclear factor kappa-B p65 (NF-κB p65) to attenuate O6-methylguanine-DNA methyltransferase (MGMT) in TMZ-resistant glioblastoma cells (U87R). Our findings proved that N45 might be a potential therapeutic agent against glioblastoma and TMZ-resistant glioblastoma, promising to be a potential agent to reduce drug resistance.

Abstract: The safety and feasibility of laparoscopic versus open liver resection (LLR vs. OLR) associated lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) are still controversial. The aim of the present study was to compare short and long-term outcomes. We reviewed data on 43 consecutive patients who underwent curative liver resection with associated lymphadenectomy for ICC. The short-term outcomes including postoperative morbidity and mortality, and the long-term outcomes including overall survival (OS) and recurrence-free survival (RFS) were compared. The median survival, 1- and 3-year OS in LLR and OLR groups were 22.5 months, 76.9% and 47.1%, and 12.1 months, 43.1% and 20.0%, respectively. The median survival, 1- and 3-year RFS in LLR and OLR groups were 10.3 months, 27.8% and 0%, and 8.1 months, 24.0% and 4.0%, respectively. The results showed that LLR obviously reduced intraoperative blood loss (median, 375 vs. 500ml, p = 0.016) and postoperative hospital stay (median, 6 vs. 9 days, p = 0.016). Moreover, there was no significant difference in short-term outcomes including postoperative morbidity (including wound infection, bile leakage, liver failure and pneumonia) and mortality within 30 days, and long-term outcomes including OS and RFS between LLR and OLR. (all p > 0.05). Multivariate analysis showed that CA19-9 level, TNM stage, and tumor differentiation were independent risk factors for OS and RFS. LLR for ICC is safety and feasibility compared with OLR. The advantage of LLR was to reduce intraoperative blood loss and postoperative hospital stay.

Abstract: C-reactive protein (CRP)- and albumin (Alb)-based scoring systems are available for predicting the prognosis of patients with diverse forms of gastrointestinal cancer, but their utility for patients with intrahepatic cholangiocarcinoma (ICC) is still unclear. This study aimed to elucidate whether a high CRP/Alb ratio is associated with the surgical outcome of ICC patients. Patients who underwent initial and curative resection for ICC were included in this study, and were divided into the High and Low CRP/Alb groups based on their preoperative CRP and Alb values. The surgical outcomes were compared between the two groups. The median CRP/Alb ratio amongst 88 patients was 0.033 (range, 0.019-3.636); 44 patients with CRP/Alb > 0.033 were allocated to the High CRP/Alb group and 44 patients were allocated to the Low CRP/Alb group. The operative data did not differ between the two groups, while the tumor status was more advanced in the High CRP/Alb group. The median overall survival was 2.4 years (95% CI, 1.4-3.3) and 8.9 years (3.8-NA) in the High and Low CRP/Alb groups, respectively (P < 0.001), and recurrence-free survival was 0.5 years (95% CI, 0.3-0.7) and 7.7 years (1.3-NA), respectively (P < 0.001). In a multivariate analysis, the independent factors for overall survival were High CRP/Alb (P = 0.017) and multiple nodules (P = 0.008). Taken together, the survival of ICC patients in the High CRP/Alb group was reduced compared to that of patients in the Low CRP/Alb group due to the advanced stage of the tumor as well as malnutrition.

Abstract: Our purpose was to explore the status of laparoscopic radical resection of hilar cholangiocarcinoma (LRRHcca) in Mainland China. Studies published before February 2020 were retrieved from CNKI database, Pubmed database and Wanfang database. Search terms included "hilar cholangiocarcinoma", "Klatskin tumor", "laparoscopy", "radical operation". Relevant articles regarding LRRHcca in Mainland China were also retrieved. 13 articles were included in this study, with a total of 189 cases. The operation time was 354 min (weighed average, WA), and the mean intraoperative blood loss was 324 mL (WA). The rate of negative margin (R0 rate) was 95.2%, and the number of lymph nodes received was 9.5 (WA). 2.6% of cases were converted to laparotomy. The incidence of postoperative complications was 21.2%, with 3.2% for those classified as Clavien-Dindo ≥ 3, 12.2% for bile leakage, 1.6% for postoperative abdominal hemorrhage, 1.6% for liver insufficiency, and 1.1% for abdominal infection. In-hospital mortality was 0.5%, with mean postoperative hospital stay of 15 days (WA), and the rate of reoperation was 1.1%. The mean postoperative follow-up time was 16 months (WA), and 1-year overall survival rate was 84.5%. In conclusions, laparoscopic radical hilar cholangiocarcinoma is safe and feasible in experienced hands after careful selection of HCCA cases.

Abstract: The new coronavirus (COVID-19) has been characterized as a world pandemic by WHO since March 11, 2020. Although it is likely that COVID-19 transmission is primarily via droplets and close contact, airborne transmission and fecal-oral route remains a possibility. The medical staff working in the operating room, such as anesthesiologists, surgeons and nurses, are at high risk of exposure to virus due to closely contacting patients. The perioperative management is under great challenge while performing surgeries for patients suffering COVID-19, including emergency cesarean section, which is one of the most common surgeries under such circumstances. How to prevent medical staff from cross-infection is an issue of great concern. In this article, we give a practice of anesthesia scenario design for emergency cesarean section in a supposed standard patient suffering COVID-19, aimed to optimize the work flow and implement the protective details through simulation of a real operation scenario, which may be useful for training and clinical practice of anesthesia management for patients suffering COVID-19 or other fulminating infectious diseases.

Abstract: A low platelet count, one of parameters of portal hypertension, is clinically a predictor of postoperative mortality, while platelets induce tumor development during growth factor secretion. In this study, we retrospectively investigated whether high platelet count negatively affects the survival of patients with hepatocellular carcinoma (HCC). Patients undergoing initial and curative resection for HCC were included. Surgical outcomes were compared between the high platelet (platelet count ≥ 20 × 104/μL) and control (< 20 × 104/μL) groups in patients without cirrhosis and between the low platelet (< 10 × 104/μL) and control (≥ 10 × 104/μL) groups in patients with cirrhosis. Among patients without cirrhosis, tumor was larger (P < 0.001) and tumor thrombus was more frequent (P < 0.001) in the high-platelet group than in the control group. After a median follow-up period of 3.1 years (range 0.2-16.2), median overall survival was 6.3 years (95% confidence interval [CI], 5.3-7.8) and 7.6 years (6.6-10.9) in the high-platelet (n = 273) and control (n = 562) groups, respectively (P = 0.027). Among patients with cirrhosis, liver function was worse (P < 0.001) and varices were more frequent (P < 0.001) in the low-platelet group. The median overall survival of patients in the low-platelet group (n = 172) was significantly shorter than that of patients in the control group (n = 275) (4.5 years [95% CI, 3.7-6.0] vs. 5.9 years [4.5-7.5], P = 0.038). Taken together, thrombocytopenia indicates poor prognosis in HCC patients with cirrhosis, while thrombocytosis is a poor prognostic predictor for those without cirrhosis.

Abstract: Irrational use of drugs remains a major challenge especially in developing countries, which contributed to a heavy pharmaceutical expenditure burden. Price regulation has been taken to curb the growth of pharmaceutical expenditures in many countries. This study aimed to investigate the impact of different mark-up drug policies on drug-related expenditures in tertiary public hospitals in Shanghai, China. Data were drawn from the audited financial statement in 24 tertiary public hospitals in Shanghai from January 2015 to December 2018. Drug-related revenue data and per capita cost data pre- and post-intervention were included. Interrupted time series design was applied to assess the actual effects of Fixed Percent Mark-up Drug (FPM) policy and Zero Mark-up Drug (ZMD) policy respectively. Results showed that ZMD policy achieved better intervention effects on declining drug-related expenditures than FPM policy. Apart from a declining trend in drug proportion (coefficient = -0.0017, p = 0.031), no other significant changes were found during FPM implementation. However, ZMD policy was associated with a level decline in per capita outpatient drug cost (coefficient = -12.21, p = 0.025) and a trend decline in per capita inpatient drug cost (coefficient = -25.12, p < 0.001), as well as a level decrease (coefficient = -0.0256, p = 0.001) and a downward tendency (coefficient = -0.0018, p < 0.001) in drug proportion. ZMD policy was effective in regulating drug-related expenditures, while FPM policy was difficult to achieve expected results due to the existence of profit space. Further regulation should be strengthened in the future, especially on drug revenue and per capita drug cost.

Abstract: Health care reform is a worldwide problem. To address the problems of costs, access, quality, efficiency, and equity, China initiated healthcare reform in 2009. The progress of China's healthcare reform has been internationally recognized as the reform has expanded insurance coverage and improved access to and reduced the costs of care over the ten-year period from 2008 to 2018. To achieve sustainable goals, attention must be focused on whether and how the reform encourages physicians. This paper highlights the role of physicians, the challenges that need to be addressed, and the direction in which to advance health reform in China from the perspective of physicians. The slow-growing and aging physician population cannot meet the ever-increasing medical demand. Physicians have a heavy workload, work long hours, have unsatisfactory income, and have a fraught relationship with patients. The situation calls for rethinking the value of physicians and rebuilding trust between physicians and patients. Further healthcare reform is needed to equitably allocate physicians with adequate training, time, and resources to deliver evidence-based practices and patient-centered care.

Abstract: The aim of this study is to assess the efficacy of multiple treatments, especially hydroxychloroquine, used in different disease stages of coronavirus disease 2019 (COVID-19). All consecutive patients with COVID-19 admitted to Shanghai Public Health Clinical Center (Shanghai, China) between January 20, 2020, and April 30, 2020, were enrolled, and their clinical data were retrospectively collected. Binary logistic regression was used to screen the factors associated with disease aggravation, and multivariable analyses with the Cox proportional hazards model were used to estimate the effects of prognostic factors on the improvement time and PCR conversion days in throat swabs and stool swabs. A total of 616 patients, including 50 (8.11%) severe and 18 (2.92%) critical patients, were enrolled in our retrospective cohort study. The early use of hydroxychloroquine was a protective factor associated with disease aggravation (95% CI: 0.040-0.575, p = 0.006). Clinical improvement by 20 days was significantly different between patients with hydroxychloroquine used early and those with hydroxychloroquine not used (p = 0.016, 95% CI: 1.052-1.647). The median time to clinical improvement was 6 days in the hydroxychloroquine used early group, compared with 9 days in the without hydroxychloroquine used group and 8 days in the with hydroxychloroquine not used early group (p < 0.001). Hydroxychloroquine used early was associated with earlier PCR conversion in both throat swabs (HR = 1.558, p = 0.001) and stool swabs (HR = 1.400, p = 0.028). The use of hydroxychloroquine at an early stage is a potential therapeutic strategy for treating patients before irreversible severe respiratory complications occur. The early use of hydroxychloroquine decreased the improvement time and the duration of COVID-19 detection in throat and stool swabs.

Abstract: Recently, an increasing number of reports have indicated that a few patients who were believed to have recovered from COVID-19 initially tested negative but later tested positive. Several hospitals in different countries have detected SARS-CoV-2 RNA in the semen and cerebrospinal fluid of patients with severe COVID-19. Given the fact that the testes and central nervous system are both immune privilege sites and the fact that Ebola virus and Zika virus can avoid immune clearance and continue proliferating and spreading by hiding in those sites, the question of whether SARS-CoV-2 is present in immune privilege sites, it attacks those sites, and it spreads again after proliferating in those sites needs to be investigated.

Abstract: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that struck in late 2019 and early 2020 is a serious threat to human health. Since there are no approved drugs that satisfactorily treat this condition, all efforts at drug design and/or clinical trials are warranted and reasonable. Drug repurposing is a well-known strategy that seeks to deploy existing licensed drugs for newer indications and that provides the quickest possible transition from the bench to the bedside to meet therapeutic needs. At present, several existing licensed drugs such as chloroquine, hydroxychloroquine, methylprednisolone, dexamethasone, and remdesivir have been used because of their potential efficacy in inhibiting COVID-19. Recently, antibiotics such as tetracyclines and macrolides have been reported to be effective against COVID-19. A combination of tetracyclines and macrolides may be a potential treatment for COVID-19 because there are some differences in the mechanism of action of tetracyclines and macrolides.

Abstract: The current study describes the technical details of and the clinical prognosis for the "China stitch", a novel technique for hand-sewn esophagojejunostomy in totally laparoscopic total gastrectomy. This study also explores the feasibility and safety of the technique. Clinical data of 20 patients with esophagogastric junction cancer in Beijing Shijitan Hospital, Capital Medical University from January 2017 to April 2018 were retrospectively analyzed. All 20 patients underwent esophagojejunostomy via a novel hand-sewn technique that uses traction to turn the left or right wall of the esophagus into an anterior wall. This avoids the difficulty of suturing the posterior wall. All patients were followed until June 2019. All 20 patients successfully underwent the procedure. The mean operating time was 216.5 ± 24.9 (176-254) min, the mean hand-sewn reconstruction time was 44.4 ± 9.4 (26-61) min, intraoperative bleeding was 141.2 ± 24.9 (130-160) mL, and the number of resected lymph nodes was 23 ± 8 (14-33). After surgery, there was one case of anastomotic leakage and one case of anastomotic stenosis, but both were alleviated with conservative treatment. The mean duration of follow-up was 15 (4-33) months. There was no significant difference in postoperative complications of and short-term oncologic prognosis for the 20 patients who underwent hand-sewn esophagojejunostomy and the 21 patients who underwent mechanical esophagojejunostomy during the same period. In conclusion, the "China stitch", a novel hand-sewn technique, is a cost-effective, safe, and reliable method for esophagojejunostomy in totally laparoscopic total gastrectomy.

Abstract: Tourette's syndrome (TS) is an inherited neurologic disorder characterized by involuntary stereotyped motor and vocal tics. Its pathogenesis is still unclear and its treatment remains limited. Recent research has suggested the involvement of immune mechanisms in the pathophysiology of TS. Microglia are the brain's resident innate immune cells. They can mediate neuroinflammation and regulate brain development and homeostasis. A traditional Chinese medicine (TCM), Ningdong granule (NDG), has been found to be efficacious in the treatment of TS while causing few adverse reactions. In the current study, a rat model of 3,3'-iminodipropionitrile (IDPN)-induced TS was used to explore the regulating effects and mechanisms of NDG on microglia-mediated neuroinflammation. IDNP led to robust pathological changes and neurobehavioral complications, with activation of microglia in the striatum of rats with TS. After activation by IDNP, microglia strongly responded to this specific injury, and TNF-α, IL-6, and MCP-1 were released in the striatum and/or serum of rats with TS. Interestingly, NDG inhibited the activation of microglia and decreased the abnormal expression of TNF-α, IL-6, and MCP-1 in the striatum and/or serum of rats with TS, thus controlling tics. However, there were no significant changes in the striatum and/or serum of rats with TS after treatment with haloperidol. The anti-TS action of haloperidol might occur not through microglial activation and neuroinflammation but through the DAT system, thus controlling tics. In conclusion, microglia might play key roles in mediating neuroinflammatory responses in TS, triggering the release of TNF-α, IL-6, and MCP-1.NDG inhibited tics in rats with TS, and this mechanism may be associated with a reduction in the increased number of activated microglia and a decrease in the expression of pro-inflammatory cytokines and chemokines in the striatum and/or serum.

Abstract: Salmonella enterica serovar Typhimurium (Salmonella), a pathogenic bacterium, is a major cause of foodborne diseases worldwide. Salmonella injects multiple virulence factors, called effectors, into cells and causes multiple rearrangements of cellular biological reactions that are important for Salmonella proliferation and virulence. Previously, we reported that Salmonella infection causes loss of MTR4 and RRP6, which are nuclear RNA degradation factors, resulting in the stabilization and accumulation of unstable nuclear RNAs. This accumulation is important for the cellular defense for Salmonella infection. In this study, we examined a series of Salmonella mutant strains, most of which are strains with genes related to effectors translocated by T3SSs encoded on Salmonella pathogenic islands, SPI-1 and SPI-2, that have been depleted. Among 42 Salmonella mutants, 6 mutants' infections canceled loss of MTR4 and RRP6. Proliferation assay of Salmonella in the cell revealed that six mutants showed poor proliferation in the host cell, demonstrating that poor proliferation contributed to cancellation of MTR4 and RRP6 loss. This result indicates that certain events associated with Salmonella proliferation in host cells cause loss of MTR4 and RRP6.