The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

Objective:To study the epidemiological characteristics and spatio-temporal aggregation of hemorrhagic fever with renal syndrome (HFRS) in Shandong Province, and to provide reference for formulating reasonable prevention and control strategies.Methods:Retrospective analysis was used to collect HFRS surveillance data and confirmed case data in Shandong Province from 2017 to 2020 in the "China Disease Prevention and Control Information System Infectious Disease Surveillance System". Geoda 1.18 software was used for global and local spatial autocorrelation analysis, SaTScan 9.6 software was used for spatio-temporal scanning analysis, and ArcGis 10.7 software was used for map drawing and visual display.Results:A total of 3 753 cases of HFRS were reported in Shandong Province from 2017 to 2020, including 56 deaths. The annual incidence rate was 1.26/100 000, 1.22/100 000, 0.75/100 000 and 0.53/100 000, respectively, with an average annual incidence rate of 0.94/100 000. The incidence of HFRS was obviously seasonal, mainly concentrated in autumn and winter from October to December, accounting for 50.41% (1 892/3 753). The age of onset was mainly 30-59 years old, accounting for 61.68% (2 315/3 753). The male to female ratio was 2.76 ∶ 1.00 (2 756 ∶ 997). The occupation distribution was mainly farmers, accounting for 81.99% (3 077/3 753). The global spatial autocorrelation analysis showed that HFRS showed spatial aggregation areas in each year from 2017 to 2020 (Moran' I = 0.38, 0.33, 0.59, 0.46, Z = 7.47, 7.23, 10.69, 8.66, P < 0.001). The local spatial autocorrelation analysis showed that "high-high" aggregation areas were mainly concentrated in central and southeast of Shandong Province, while "low-low" aggregation areas were mainly concentrated in northwest of Shandong Province. Spatio-temporal scanning analysis revealed 1 type Ⅰ agglomerations and 2 type Ⅱ aggregation areas. The type Ⅰ aggregation areas occurred from October to November 2018, covering 22 counties (districts) of 5 cities in Qingdao, Yantai, Weifang, Weihai and Rizhao. The first type Ⅱ aggregation area occurred from October to November 2017, involving 23 counties (districts) of 8 cities in Jinan, Zibo, Zaozhuang, Weifang, Jining, Tai 'an, Rizhao and Linyi. The second type Ⅱ aggregation area occurred in Jinxiang County, Jining City from February to March 2017. Conclusion:The incidence of HFRS in Shandong Province from 2017 to 2020 has obvious spatio-temporal aggregation, and the hot spots are concentrated in central and southeast of Shandong Province, which should be regarded as a key area for prevention and control of HFRS.

Hospital culture plays an important role in the orderly operation of large shelter hospitals as well as epidemic prevention and control.From April to May 2022, the shelter hospital of the National Convention and Exhibition Center(Shanghai) had created the large shelter hospital culture co-built by doctors and patients with a greater sense of belonging by taking measures such as joint party building between doctors and patients, giving play to the vanguard force of party members, carrying out various forms of cultural, sports and science popularization activities, encouraging enthusiastic patients to participate in activity planning, focusing on key groups, formulating shelter " residents convention", and so on. These measures ultimately formed cultural adaptation, cultural synchronization and cultural shaping, which were conducive to enhancing the empathy of doctors and patients, improving the effectiveness of medical implementation, and promoting the standardization of shelter management system. This harmonious, warm and autonomous culture co-built by doctors and patients effectively ensures the safe and orderly operation of the shelter hospital, and provides reference for the construction of the cultural system of large shelter hospitals in China.

Objective:To evaluate the effect of position change and pneumoperitoneum pressure on the respiratory system of patients undergoing DaVinci assisted laparoscopic prostate cancer surgery.Methods:Peak airway pressure, lung compliance and airway resistance were recorded by ventilator as the basic values to evaluate the change of respiratory function. When the artificial pneumoperitoneum pressure was 10 mmHg or 15 mmHg, the changes of respiratory function were recorded in five different positions: trendelenburg position (head low foot height) 30°, 15°, supine position, anti-trendelenburg position (head high foot height) 15° and 30°, peak airway pressure, lung compliance, airway resistance and so on.Results:At 10 mmHg and 30° trendelenburg, peak airway pressure, lung compliance and airway resistance were 28.13 cmH 2O, 23.33 ml/cmH 2O,16.06 cmH 2O·L -1·Sec -1, respectively. When the pneumoperitoneum pressure was adjusted to 15 mmHg, peak airway pressure increased to 32.03 cmH 2O, lung compliance decreased to 20.14 ml / cmH 2O, and airway resistance increased to 117.24 cmH 2O·L -1·Sec -1( P<0.01). At 10 mmHg and trendelenburg returned to 15°, peak airway pressure, lung compliance and airway resistance were 26.66 cmH 2O, 24.95 ml/cmH 2O,15.50 cmH 2O·L -1·Sec -1, peak airway pressure increased to 30.61 cmH 2O, the lung compliance decreased to 20.89 ml/cmH 2O and airway resistance increased to 16.66 cmH 2O·L -1·Sec -1 ( t value was -43.81, 24.638, -12.812, P<0.01). Conclusion:With the increase of trendelenburg position angle and artificial pneumoperitoneum pressure, the peak airway pressure and airway resistance are increased, while the lung compliance decreases gradually. Compared with trendelenburg position, the change of artificial pneumoperitoneum pressure has more influence on respiratory function.

Objective To investigate the relationship between the serum levels of retinol-binding protein 4(RBP4),blood lipid level and glycemic control in patients with chronic schizophrenia complicated with type 2 diabetes.Methods The levels of glycated hemoglobin (HbA1c),fasting plasma glucose (FPG),cholesterol (TC),triglycerides (TG),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),apolipoproteinA1 (Apo A1),apolipoprotein B(Apo B),apolipoprotein E(Apo E),lipoprotein(a)[Lp (a)],free fatty acid(FFA),RBP4,fasting insulin (FINS) were determined in 96 patients with chronic schizo-phrenia complicated with type 2 diabetes (schizophrenia group) and 50 healthy subjects (healthy control group),the insulin resistance index (HOMA IR)was calculated.The patients were divided into HbA1c<7.0% group and HbA1c≥7.0% group according to the results of the HbA1c,and the results were statistically analyzed.Results In the HbA1c<7.0% group,the levels of HbA1c,FPG,TG,Apo B,Apo E,Lp(a),RBP4 were significantly higher than those in the healthy control group,the levels of serum Apo A1 and HDL-C was lower than those in the healthy control group (P<0.05).In the HbA1c≥7.0% group,the levels of HbA1c, Body mass index (BMI),FPG,TG,Apo E,FFA,RBP4,FINS,HOMA-IR were significantly higher than those in the HbA1c<7.0% group and the healthy control group,the levels of TC,Apo B,Lp(a)were significantly higher than the healthy control group and the levels of serum Apo A 1 and HDL-C were lower than those in the healthy control group (P<0.05).Single factor Logistic regression analysis showed that BMI,TG,Apo E, FFA,RBP4,FINS and HOMA-IR were risk factors for poor control of blood glucose in type 2 diabetes pa-tients with chronic schizophrenia.Conclusion The levels of RBP4 and blood lipid in patients with chronic schizophrenia complicated with type 2 diabetes may be related to the poor control of blood sugar level.

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs ) on vascular endothelial growth factor ( VEGF ) and monocyte chemoattractant protein-1 ( MCP-1 ) of acute myocardial ischemia-reperfusion (AMI-R) injury in rats. Methods 24 Sprague-Dawley rats were randomly divided into sham group, AMI-R group and UCMSCs treatment groups on average. The rats were sacrificed on the 10th day after UCMSCs transplantation, and the myocardial tissues below the ligature were taken. The mRNA and protein expressions of MCP-1 of the tissue were detected by RT-PCR and Western Blot respectively, and the expression of VEGF protein was detected by immunohistochemistry. Results The relative expression levels of MCP-1 mRNA and the protein in UCMSCs group were significantly lower than those in sham group and AMI-R group (all P<0.05). The expression of VEGF protein in UCMSCs group was significantly higher than that in sham group and AMI-R group, the differences were statistically significant(all P<0.05). Conclusion UCMSCs transplantation can promote the angiogenesis and decrease the inflammation reaction in the treatment of acute myocardial ischemia-reperfusion injury.

Objective· To investigate the association between neck circumference (NC) and cardiovascular risk factors among middle-aged and elderly people without diabetes in Jiading District in Shanghai.Methods· A cross-sectional study was conducted among 4 657 nondiabetic inhabitants aged 40 and above in Jiading District,Shanghai from August 2014 to July 2015.Clinical information collection,anthropometric measurements,and biochemical analyses were performed.The objects were divided into 4 groups according to the quartiles of NC in order to analyze association between NC and cardiovascular risk factors.Results· With increase of NC,the prevalences of abdominal obesity,insulin resistance,hypertension,and dyslipidemia all increased as well as waist circumference,body mass index (BMI),blood pressure,lipid profile,fast blood glucose,and HOMA-IR level (all Ptrend ＜0.01).Multiple Logistic regression analysis showed that individuals in Q2,Q3 and Q4 group had significantly higher risk of abdominal obesity,insulin resistance,hypertension,and dyslipidemia compared with those in Q1 group after age,sex,smoking,drinking,physical activity,BMI,waist circumference,systolic blood pressure,C-reactive protein,fast blood glucose,and lipid profile were corrected (all Ptrend ＜0.01).Conclusion· NC is positively and independently correlated with cardiovascular risk factors in middle-aged and elderly nondiabetic people in Jiading District in Shanghai.

Objective This study aimed to investigate the associations between adipose tissue distribution and risks of macro-vascular complications in type 2 diabetic patients. Methods The study included T2DM patients either previously diagnosed by questionnaire or newly diagnosed with fasting plasma glucose(FPG)≥7. 0 mmol/L and/or 2 hour postprandial glucose ( 2h PG )≥11. 1 mmol/L from residents older than 40 years from Jiading Community, Shanghai, China(n=10 375). Each participant had gone through anthropometric measurements, blood tests, vascular function tests including carotid intima-media thickness ( CIMT ) , ankle-brachial index ( ABI ) , branchial-ankle pulse wave velocity( baPWV) as well as carotid plaques. Results WHR quartiles was significantly associated with high risks for ten-year cardiovascular disease risks [ ASCVD high risk: OR:1. 17 ( 1. 05-1. 31 );Framingham high risk:1. 13(1. 00-1. 29)]. However, WHR has no significant relations with risks of increased carotid intima-media thickness( CIMT) , abnormal ankle-brachial index( ABI) , increased brachial ankle pulse wave velocity( baPWV) or carotid plaques. Conclusions In type 2 diabetic patients, abdominal adipose tissue has an independent role in high risk for ten-year cardiovascular diseases. However it has no relations with other vascular functions including increased CIMT, abnormal ABI, increased baPWV, or carotid plaque.

OBJECTIVETo investigate the predominance ticks and the infectious status of severe fever with thrombocytopenia (SFTSV) in Penglai and Laizhou counties, Shandong province.

METHODSTwo towns with high incidence rate were selected in Penglai and Laizhou, respectively, then three villages were selected in each towns. Parasitic ticks were collected from the host skin by hand manually and free ticks manually with white cloth from the grassland, monthly, during April to December in 2011. Samples were classified by original, varieties, developmental stages, then extracted RNA, using Realtime RT-PCR to test severe fever thrombocytopenia syndrome virus, S fragments were amplified with nested PCR, then isolated virus. By neighbor joining method in the phylogenetic tree, the minimum infection rate (MIR) was used to represent the infection status of ticks in novel bunyavirus.

RESULTSA total of 3 145 ticks were collected totally from 5 categories, there were 3 048(96.92%) of Haemaphysalis longicornis, 73(2.32%) of Rhinpicephalus sanguineus, 10(0.32%) of microplus Boophilus, 9(0.29%) of Haemaphysalis campanulata, 5(0.16%) of Dermacentor sinicus, respectively. The positive rate of nucleic acid of 2 044 samples was 6.16% (126/2 044), minimum infection rate (MIR) was 4.01%, there were 122(96.83%) of Haemaphysalis longicornis, 3(2.38%) of Rhinpicephalus sanguineus, and 1(0.79%) of microplus Boophilus, MIR was 4.00%, 4.11%, and 10.00%, respectively. There were no nucleic acid positive samples in Haemaphysalis campanulata and Dermacentor sinicus. The 11 S segments were amplified in 126 positive samples, the homology of S fragment was 95.6%-99.9% with 11 strains isolated from the identified SFTS cases in local area, 3 strains isolated from animals, and 11 strains isolated from other areas. There was no significant difference among original, varieties and developmental stages.

CONCLUSIONHaemaphysalis longicornis was the predominant species in Penglai and Laizhou counties, it could be propagation medium with Rhipicephalus sanguineus and microplus Boophilus, S sequence in ticks was higher homology with virus isolated from local SFTS cases.