OBJECTIVE To establish a method for determining the content of 11 antioxidants and their degradation products in recombinant Exendin-4-FC fusion protein injection by HPLC. METHODS The protein was precipitated with saturated ammonium sulfate. After centrifugation, the supernatant was transferred to a C18 solid phase extraction cartridge activated by methanol. Then the cartridge was eluted with 4 mL of methanol and 5 mL of ethyl acetate respectively, and the eluent was diluted with methanol-ethyl acetate(2∶3) mixed solvent and passed through a 0.22 µm PTFE hydrophobic filter. It was analyzed by HPLC and quantified by external standard method. Chromatographic conditions: Kinetex® XB-C18 100Å (100 mm×4.6 mm, 2.6 µm)column, the detection wavelength was 230 nm, the column oven was 30 ℃, the injection volume was 5 µL and the flow rate was 0.4 mL·min–1, mobile phase was 0.1% formic acid-methanol(A)-0.1% formic acid aqueous solution(B), the running time was 45 min. RESULTS The 11 target substances showed a good linear relationship in the range of 2.5−35 μg·mL–1 with R2 ≥0.99. At three different concentration(25, 10, 5 μg·mL–1) of spiked samples, the average recovery rates of 11 antioxidants ranged from 88.1% to 106.5%, with RSDs in the range of 0.10%–9.05%. The RSDs of 6 repeatable samples was 2.01%–4.77%, which of 12 intermediate precision samples was 2.58%–9.75%. The positive/inverted samples of three batches of recombinant Exendin-4-FC fusion protein injection were detected at 0 month, 3 months and 6 months(25 ℃), and the results showed that there was no antioxidant and its degradation leaching in all batches of samples at different detection points. CONCLUSION The method has good specificity, high accuracy and precision, good solution stability, high durability and can be used for the content detection of antioxidants in drugs.

Objective To understand the molecular characteristics of Streptomycin(SM)resistance in multidrug-resistant tuberculosis(MDR-TB)in Jiangxi Province,and to explore the relationship between SM resistant genes(rpsL,rrs and gidB)mutations and SM resistant phenotypes in Beijing genotype TB.Methods 106 non-replicated MDR-TB isolates were collected from Gaoxin Branch of The First Affiliated Hospital of Nanchang University and Jiangxi Provincial Chest Hospital from January to December 2021,and tested for drug-resistance phenotypes,whether they were Beijing genotype or not and the characteristics of rpsL,rrs and gidB gene mutations.Chi-square test was performed to determine whether rpsL,rrs and gidB mutations were related to genotypes and drug-resistance phenotypes.Results Among 106 cases of MDR-TB,76 cases were resistant to SM.A total of 58 cases had rpsL 43A>G mutation,8 cases had 88A>G mutation,5 cases had rrs mutation,and 3 cases had gidB mutation.Statistical analysis showed that the coincidence rate of gene mutation and phenotypic drug-resistance detection was 89.6%,and the specificity and sensitivity were 86.7%and 90.8%,respectively.The isolated rate of Beijing genotype TB was 88.7%,and the drug-resistant gene mutations were mainly concentrated in rpsL and rrs,while the drug-resistant mutations of non-Beijing genotype were mainly concentrated in gidB;in addition,Beijing genotype bacteria were more prone to gene mutations(P = 0.013),but there was no difference in phenotypic drug-resistance.Conclusions Mutations in rpsL,rrs,and gidB genes have a good coincidence rate with phenotypic drug-resistance,and molecular biology can be used to detect directly drug-resistance genes to predict bacterial resistance;TB genotypes are strongly associated with streptomycin resistance characteristics.

Objective To investigate ecological isolation between Oncomelania hupensis snail populations in hilly regions and marshland and lake regions in Yuanjiang valley, Changde City, Hunan Province, and to unravel its underlying mechanisms. Methods Taoyuan County, Shimen County, Linli County and Lixian County in Changde City were selected as snail sampling sites in hilly regions, and Lixian County, Jinshi City, West Lake Administration District, Hanshou County and Dingcheng District were selected as snail sampling sites in marshland and lake areas. Cytochrome C oxidase 1 (cox 1) gene was amplified in snail samples and sequenced. The genetic sequences of O. hupensis snails were aligned using the software MEGA 11, and the haplotypes of O. hupensis snails were determined using the software DNASP 5.10.01. The phylogenetic tree was generated using Bayesian inference with the software MrBayes 3.2, and analysis of molecular variance (AMOVA) was performed to analyze the source of genetic divergence and estimate the genetic divergence index (F_ST) among snail populations with the software Arlequin 3.5.2.2. The genetic barrier among 11 O. hupensis snail populations was estimated using the Monmonier algorithm of adegenet toolkit in R package. The settings with “land in winter and water in summer” in the Yuanjian River section were divided into two categories according to the upstream and downstream, and the areas with “land in winter and water in summer” in the upstream and downstream were transformed into raster data, and then loaded into the software Fragstats 4 for analysis of landscape indicators. The trends in changes of digital elevation were extracted from the Yuanjiang River section based on the digital elevation model, and made three-dimensional visualization using the R package. Results The mitochondrial cox 1 gene were amplified in 165 O. hupensis snais from 11 sampling sites and sequenced, and a total of 152 valid gene sequences were obtained, with 46 haplotypes or 9 populations determined. No haplotype was shared in snails between Taoyuan County and Dingcheng District and Hanshou County along the downstream of the Yuanjiang River. The total area of settings with “land in winter and water in summer” was 617.66 hm² in the upsteram of the Yuanjiang River, which consisted of 473 patches, with each patch measuring 1.31 hm², the largest area index of 0.735 2, the landscape division index of 0.999 9, and the landscape shape index of 45.293 7. The total area of settings with “land in winter and water in summer” was 9 956.92 hm² in the downstream of the Yuanjiang River, which consisted of 771 patches, with each patch measuring 12.91 hm², the largest area index of 97.839 9, the landscape division index of 0.042 7, and the landscape shape index of 7.249 6. The area of settings with “land in winter and water in summer” was much larger in the downstream than that in the upstream of the Yuanjiang River, and the stronger landscape connectivity and non-remarkable alteration of riverbed elevation provided suitable habitats for snail breeding. Conclusion The hydrological and environmental characteristics of the upstream of the Yuanjiang River restrain the breeding and spread of O. hupensis, resulting in ecological isolation between Oncomelania hupensis in Taoyuan County and those in the downstream of Yuanjiang River.

OBJECTIVE To understand the future development trend of dispensing and use for preparations of medical institutions，and to provide countermeasures and suggestions for promoting the high-quality development of application and dispensing use for preparations of medical institutions . METHODS The development history of dispensing and use for preparations of medical institutions of China was reviewed as a whole ，and then the differences of domestic dispensing and use institutions for preparations of medical institutions over the years were compared from different perspectives ；and the differences between domestic institutions and Japan ’s hospital preparation dispensing and use institutions were compared. The development trend of dispensing and use for preparations of medical institutions of China was summarized to put forward countermeasures and suggestions. RESULTS & CONCLUSIONS The development process of dispensing and use for preparations of medical institutions of China could be roughly divided into the initial stage （2001-2004），the forming stage （2005-2018） and the development stage （2019-present）. Year by year ，the dispensing and use institutions of preparations of medical institutions had shown that the scope of dispensing and use had been expanded ；the approval process had been accelerated ，and the responsibilities of all parties had been clearly defined. Compared with Japan ，regulatory model for preparations of medical institutions was relatively simple in China. In the future ，the large-scale promotion and application of preparations of medical institutions will be normalized ，the time limit for dispensing approval will be shortened ，the approval process will be simplified ，the access threshold for dispensing and use will be gradually lowered ，and the supervision of dispensing and use will be strengthened during and after the event. It is recommended to strictly control the quality and safety of preparations of medical institutions ，implement classified management of use for preparations of medical institutions ，and further improve the supervision mechanism during and after the event.

Systemic sclerosis (SSc) is an autoimmune rheumatic disease that is characterized by skin fibrosis with multi-organ involvement. In China, the standardized diagnosis and treatment for SSc is still lacking. Based on the diagnosis criteria and guidelines from China and abroad, Chinese Rheumatology Association developed the current standardization of diagnosis and treatment for SSc. The purposes of this guideline are to standardize clinical management for SSc in China, to interpret the key evaluation tools for SSc, and to recommend therapeutic principle and strategies.

Under the background of " Internet+ medical treatment" and the continuous deepening of face recognition technology research, the face recognition industry has continued to mature, and face recognition has been initially applied in medical fields such as hospital management, auxiliary medical care, and epidemic prevention and control. At the same time, face recognition technology brings problems including error risk, technical cracking risk, privacy risk, equality risk, abuse risk, and other issues in practice, which seriously threaten the personal and property rights and interests of the public. On the basis of summarizing the specific application direction of face recognition technology in hospitals, the authors sorted out the legal regulation of face recognition in China, and proposed that it should be based on technology research and development, strengthen the " gatekeeper" responsibility of medical institutions, improve legal system and recommendations for strengthening judicial leadership in order to improve the legal regulations of face recognition technology, reduce the risk of infringement by medical institutions in the application of face recognition technology, and protect the legitimate rights and interests of citizens.

OBJECTIVE：To know about the current situation and trend of encouraged generic drug catalogue policy in China ， and to put forward countermeasures and suggestions for the better implementation of the policy. METHODS ：The evolution of encouraged generic drug catalogue policy in China ，the characteristics of 2 batches of included types in encouraged generic drug catalogue，the implementation effect of the first batch of encouraged generic drug catalogue ，the development trend and existing problems of encouraged generic drug catalogue policy were analyzed to put forward corresponding suggestions. RESULTS & CONCLUSIONS：The evolution of encouraged generic drug catalogue policy in China can be roughly divided into embryonic stage，policy design stage and policy implementation and adjustment stage. The first batch of included types in encouraged generic drug catalogue are mainly drugs whose patents are about to expire and the competition is insufficient ，drugs with clinical necessity ， definite curative effect and short supply ，and varieties for special clinical purposes such as the prevention and treatment of major infectious diseases and rare diseases ，and children ’s use. The second batch of included types in encouraged generic drug catalogue are mainly those with expired patents （about to expired ）and insufficient competition ，and also those with special clinical uses. Among the types of the first batch of encouraged generic drug catalogue ，the number of abbreviated new drug application （ADNA） increased by 18，involving a total of 8 varieties；only 3 ADNA were included in the priority review ，accounting for 16.67％. In 2019 and 2020，218 and 119 varieties were newly included in the medical insurance catalogue ，and 3 varieties were newly included in the encouraged generic drugs catalogue （accounting for 1.4％ and 2.5％ respectively）. At present ，encouraged generic drug catalogue policy in China has the trend and characteristics of patent oriented regression ，lack of priority review and approval system，and enhanced linkage with the medical insurance catalogue. It is suggested to adhere to the original intention of the Opinions of the State Council on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices in 2017，continue to adhere to the patent orientation of encouraged generic drug catalogue ，and improve the priority review system of generic drugs in the catalogue ，explore the “first imitation market monopoly period ”system in line with the characteristics of encouraged generic drug catalogue policy in China with reference to the U.S. FDA competitive imitation therapy guidelines ，and further strengthen the cooperation between government departments in the implementation of the encouraged generic drug catalogue policy.

Objective: To investigate the clinical efficacy of cevimeline as a pharmacotherapeutic approach to stimulating gland activity in improving the symptoms and signs of primary Sjögren syndrome (pSS). Methods: Sixty-three patients diagnosed with pSS who attended the Affiliated Huai'an Hospital of Xuzhou Medical University from January 2018 to September 2019 were included in this trial. They were randomly assigned to the therapeutic group and control group. All patients were recalled at baseline and after 2 weeks, 3 months and 6 months. Measurement of salivary and lacrimal flow as well as evaluation of subjective symptoms was performed at the follow-up. Results: Fifty-eight patients completed the trial and were included in the statistical analysis. There was a significant difference between the two groups in the measurement of salivary and lacrimal flow at the second week and third month (P < 0.05). Improvement in subjective symptoms of oral, ocular and gland was detected at the third month (P < 0.05). At the sixth month, compared with the control group, only the salivary gland symptom score of the treatment group was statistically significant (P < 0.05). Conclusion Cevimeline has good specificity and safety and can increase salivary and lacrimal flow and improve subjective symptoms of pSS in a short time.

Objective:To analyze the risk of missed diagnosis in patients with PI-RADS score>3 and negative prostate initial biopsy and to explore its risk factors.Methods:The clinical data of 268 patients with negative prostate biopsy in Northern Jiangsu People's Hospital from May 2013 to December 2018 were retrospectively analyzed. The patients were divided into observation group (PI-RADS score>3) and control group (PI-RADS score≤ 3) according to different PI-RADS scores. There were insignificant differences in age [(67.4(60.0, 74.0)years and 65.6(66.5, 72.0)years], prostate volume of initial biopsy [62.4(40.0, 72.0)ml and 60.8(38.0, 77.0)ml], biopsy cores [ 20.6(18.0, 22.0)cores and 20.4(18.0, 22.0)cores] between the observation group (n=124) and the control group(n=144)(all P>0.05). But there were significant differences in PSA [17.5(6.5, 23.0)ng/ml and 11.5(6.3, 12.0)ng/ml], PSAD[0.316(0.128, 0.363)ng/ml 2 and 0.211(0.106, 0.256)ng/ml 2], prostate inflammation of the initial biopsy [70 (56.5%) and 32 (22.2%)] between the observation group and the control group(all P<0.05). According to the follow-up results after the initial biopsy, the two groups of repeated biopsy were compared.Furthermore, Logistic regression was used to conduct univariate and multivariate analysis to explore the risk factors of patients with PI-RADS>3 for positive repeated biopsy. At the same time, the receiver operating characteristic curve (ROC curve) was used to analyze the accuracy of the risk factors. Results:There were significant differences in repeated biopsy rate [ 27.4%(34/124)and 14.6%(21/144)], CsPCa detection rate[ 41.4%(14/34) and 4.8%(1/21)]between the observation group and the control group(all P<0.05). The positive rate of repeated biopsy in the observation group (41.1%) was higher than that in the control group (23.8%), but there was no statistical difference ( P=0.248). The risk of positive repeated biopsies in the observation group was 2.24 times than that in the control group. Univariate analysis found repeated biopsy PSA ( P =0.02, OR=1.438, 95% CI 1.161-1.896), PSA ratio (repeated biopsy PSA/initial biopsy PSA) ( P=0.011, OR=10.087, 95% CI 1.714-59.36) were risk factors for positive of repeated biopsy in patients with PI-RADS score >3. Multivariate analysis also found that repeated biopsy PSA ( P=0.017, OR=1.15, 95% CI 1.076-2.123), PSA ratio ( P=0.032, OR=10.2, 95% CI 0.883-116.168) were risk factors for positive repeated biopsy. ROC curve analysis, the accuracy of repeated biopsy PSA (AUC=0.971, P<0.001, 95% CI 0.926-1.000), PSA ratio (AUC=0.839, P=0.001, 95% CI0.707-0.971) to predict positive of repeated biopsy were high. The cut-off values were 21.3 ng/ml and 1.4, respectively. The accuracy was higher when combines repeated biopsy PSA with PSA ratio (AUC=0.993, P<0.001, 95% CI 0.974-1.000). Conclusions:Patients with negative PI-RADS score > 3 have a higher risk of missed diagnosis of CsPCa than those with PI-RADS score≤3. When PSA>21.3 ng/ml and PSA ratio>1.4 during follow-up, the possibility of missed diagnosis in the initial biopsy is high.

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.