Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

Objective To evaluate the effect of modified vertical tooth preparation with full zirconium crown resto-ration in molar area.Methods A randomized study was conducted in 84 patients with all-ceramic crown restoration of posterior teeth.90 full crown restorations were collected and randomly divided into two groups:45 teeth in exper-imental group were treated with modified vertical tooth preparation,while 45 teeth in control group were treated with conventional horizontal tooth preparation with full zirconium crown restoration.When patients wore teeth,the resto-ration effects of the two groups were evaluated respectively,and then the marginal and internal fitness of the two groups were measured by silicone rubber replication method;gingival index(GI)and sulcus bleeding index(SBI)scores were recorded 6 months after wearing teeth.Results The results of chair-side evaluation of the two groups showed that the marginal fitness of the experimental group was better than that of the control group,and the differ-ence was statistically significant(P=0.036);the measured value of marginal fitness of prostheses in experimental group was better than that in control group,and the difference was statistically significant(P＜0.001);after 6 months,there was no mechanical complication between the two groups,and there was no significant difference in GI and SBI scores of periodontal soft tissue indexes.Conclusion Modified vertical tooth preparation abutment can significantly improve the marginal fitness of all-ceramic crown,which will not change the health status of peri-crown gingiva.

Objective:To study the complications and prognosis of extremely premature infants(EPIs) with gestational age (GA) <28 w.Methods:From January 2016 to December 2020, EPIs with GA <28 w admitted to NICU of our hospital were retrospectively studied. Clinical data of the infants and their mothers during pregnancy were reviewed. According to the prognosis, the infants were assigned into the survival group, the death group and the withdrawal group. According to GA, the infants were assigned into <26 w goup, 26~26 +6 w group, ≥27 w group. According to birth weight (BW), the infants were assigned in to ≤750 g group, 750~999 g group and ≥1 000 g group. SPSS 26.0 was used for data analysis. Results:A total of 265 EPIs were included, 122 (46.0%) in the survival group, 47 (17.7%) in the death group and 96 (36.2%) in the withdrawal group. GA and BW of the survival group were significantly higher than the death group and the withdrawal group ( P<0.05). The incidences of tracheal intubation (92.2%) and pulmonary hemorrhage (42.2%) in the death group were the highest among the three groups. The survival group had the highest application of prenatal glucocorticoids (80.3%) and pulmonary surfactants (99.2%) ( P<0.05). In the survival group, the top 3 common complications were bronchopulmonary dysplasia (BPD) (68.0%), pulmonary infections (65.6%) and neonatal sepsis (34.4%). The survival rate increased with GA and BW. Conclusions:The survival rate of EPIs is closely correlated with GA and BW. EPIs with pulmonary hemorrhage and tracheal intubation have poor prognosis. Prenatal glucocorticoids and pulmonary surfactant may improve clinical outcome. BPD and pulmonary infections are common complications of surviving EPIs.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To investigate the rationality and surgical errors in countermeasures against difficult removal of screws so as to provide reference for standardization of technical procedures.Methods:A retrospective study was conducted to analyze the data of 99 patients who had encountered difficult removal of screws in operative removal of internal fixation at Department of Orthopaedics, Wuxi NO.9 People's Hospital Affiliated to Suzhou University from January 2018 to May 2022. There were 62 males and 37 females with an average age of 38.8±14.7 years. Their internal fixation time ranged from 7 months to 11 years. The irrationality was defined as insufficient preoperative preparation or a countermeasure that failed to follow the surgical indications or scientific principles of minimal injury or priority of simplicity. A surgical error was defined as unnecessary injury, failed removal or complications related to operation. Cases of irrationality and surgical errors were analyzed to find associations between them.Results:The operative removal was successful in 92 cases and failed in 7 cases. Of the patients who experienced difficult removal of screws, irrationality was found in 26.3% (26/99) and a surgical error or errors occurred in 28.3% (28/99). In the patients with countermeasure irrationality, the incidence of surgical errors was 53.9% (14/26) while in those without countermeasure irrationality, the incidence of surgical errors was 19.2% (14/73), showing a statistically significant difference ( χ2=11.360, P<0.001). In the patients with surgical errors, the incidence of countermeasure irrationality was 64.3% (18/28) while in the patients without surgical errors, the incidence of countermeasure irrationality was and 11.3% (8/71), showing a statistically significant difference ( χ2=29.148, P<0.001). In the patients with failed removal, the rate of countermeasure irrationality was 85.71% (6/7) while in those with successful removal, the rate of countermeasure irrationality was 21.7% (20/92), showing a statistically significant difference ( χ2=13.748, P<0.001). Conclusions:Close relationships exist between countermeasure irrationality, surgical errors and failed removal. The higher proportion of countermeasure irrationality, the higher possibility of surgical errors. Therefore, following the rationality principle may avoid or reduce surgical errors in difficult removal of screws.

Objective:To investigate the protective effect of interfering peptide TAT-GluA2CT on hippocampal neurons in the Lithium chlorine-Pilocarpine status epilepticus model and the optimal time of administration.Methods:Male SD rats (72 cases) were induced to status epilepticus by using Lithium chlorine-Pilocarpine, while a control group ( n=12) was established.The 72 rats were divided into epilepsy group ( n=12), TAT-sham peptide group ( n=12), TAT-GluA2CT peptide group ( n=48) according to the random number table method, and the TAT-GluA2CT peptide group were further divided into the pre-1 h group ( n=12), the post-2 h group ( n=12), the post-4 h group( n=12), and the post-6 h group ( n=12) according to the administration time of the TAT-GluA2CT peptide.Nissl staining and terminal dUTP nick end labeling (TUNEL) assay were performed on 6 rats each from control group, epilepsy group, TAT-shampeptide group, pre-1 h group, post-2 h group, post-4 h group, and post-6 h group to observe the morphological changes and apoptosis of neurons in the CA1 region of the rat hippocampus.Western blot and co-immunopercipitation test were used to detect the expression of GluA2[second subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) recepter] and the coupling of GluA2/transmembrane AMPA receptor regulatory protein (TARP γ-8) complex in control group, epilepsy group, pre-1 h group, post-2 h group, post-4 h group and post-6 h group.The t-test was used to compare the data differences between 2 groups, and one-way ANOVA was adopted to compare the differences between the groups. Results:Compared with the epilepsy group, the number of neurons in each TAT-GluA2CT peptide group increased significantly, and the difference was statistically significant( epilepsy group 20.07±3.51, pre-1 h group 39.40±2.39, post-2 h group 38.43±2.42, post-4 h group 30.30±2.55, and post-6 h group 27.93±3.20, F=235.28, P<0.05). Compared with the epilepsy group, the number of apoptotic cells in each TAT-GluA2CT peptide group was significantly reduced, and the difference was statistically significant(epilepsy group 31.47±3.19, pre-1 h group 7.30±3.45, post-2 h group 9.27±3.81, post-4 h group 12.86±3.08, and post-6 h group 14.43±3.13, F=248.60, P<0.05). Compared with the control group, the expression of hippocampal GluA2 decreased after epilepsy induction, and the difference was statistically significant(control group 21 626.53±2 700.58, epilepsy group 14 578.16±2 917.02, pre-1 h group 13 375.47±3 180.54, post-2 h group 15 244.10±1 390.41, post-4 h group 15 799.16±4 559.49, post-6 h group 15 722.95±1 756.01, F=3.83, P<0.05). No statistical difference was observed in the expression of GluA2 between the TAT-GluA2CT peptide group and the epilepsy group( F=0.45, P=0.77). Compared with the epilepsy group, GluA2/TARPγ-8 complex coupling was decreased in each TAT-GluA2CT peptide group, and the difference was statistically significant(epilepsy group 24 509.80±3 718.54, pre-1 h group 12 055.18±5 847.11, post-2 h group 9 630.51±5 805.17, post-4 h group 12 749.35±7 108.45, post-6 h group 11 092.98±7 330.08, F=10.68, P<0.05). Compared with the epilepsy group, the incubation period of seizures in the pre-1 h group was prolonged and the seizure rating was decreased, with statistically significant differences[epilepsy group (18.58±3.99) min, pre-1 h group (103.25±9.21) min, t=29.23, P<0.05]. Conclusions:TAT-GluA2CT peptide can attenuate the neuronal damage in hippocampus of epileptic rats.The neuroprotective effect of TAT-GluA2CT peptide was most obvious at 1 h before or 2 h after administration of Pilocarpine.

ObjectiveTo analyze the characteristics of death and premature death of 4 major chronic diseases （cardiovascular and cerebrovascular diseases， malignant tumors， chronic respiratory diseases and diabetes） in Taizhou City from 2011 to 2018，and provide data basis for the government to formulate chronic disease prevention planning. MethodsThe death data of household registration residents in Taizhou City from 2011 to 2018 were derived from the Chronic Disease Surveillance Information Management System in Zhejiang Province. The death toll ratio of chronic diseases， the mortality rate of chronic diseases， the probability of premature death of chronic diseases were analyzed. The standardization rate was calculated six times in 2010. Population composition of the census. The Joinpoint Regression Program 4.2 software was used for calculating annual percent change （APC） and its statistical test results. ResultsFrom 2011 to 2018， there were 231 724 chronic disease deaths in Taizhou City， with a mortality rate of 486.52/10⁵ and a standardized mortality rate of 381.55/10⁵. The proportion of chronic disease deaths to total deaths was 79.89%， of which males were higher than females and rural areas were higher than urban areas.From 2011 to 2018， the standardized mortality and early death probability of cardiovascular and cerebrovascular diseases， malignant tumors and chronic respiratory diseases in Taizhou showed a downward trend （P<0.05）， the standardized mortality of diabetes （P=0.46） and the early death probability （P=0.22） did not decline， and the mortality of all age groups of the above four types of chronic diseases in rural areas was higher than that in urban areas. The mortality of the four types of chronic diseases from high to low are cardiovascular and cerebrovascular diseases， malignant tumors， chronic respiratory diseases and diabetes， and the mortality tends to increase with age. From 2011 to 2018， the probability of premature death from four types of chronic diseases in Taizhou City showed a downward trend， from 13.49% in 2011 to 10.49% in 2018， with an average annual decrease of 2.97%. The difference was statistically significant （t=‒5.83，P<0.05）. ConclusionChronic disease death is the main cause of death in Taizhou City. In order to reduce the mortality rate of chronic diseases， effective prevention and control measures for chronic diseases should be carried out， especially the prevention and control of diabetes and male chronic diseases.

Objective:To investigate the diagnostic and prognostic value of D-dimer level in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods:A total of 142 cases diagnosed with ACLF were randomly selected as research objects in the open cohort using the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF). Plasma D-dimer levels were compared between patients with ACLF and non-ACLF and patients with different ACLF grades. Survival and death group D-dimer levels were compared with the end points of 28 days and 90 days, respectively. The correlation between D-dimer and other laboratory indicators and prognostic scores were investigated. Area under receiver operating characteristic curve (AUROC) was used to evaluate the D-dimer value for predicting the prognosis of ACLF patients. 125 external ACLF cases were used for validation. A Student t test or Mann-Whitney U test was used to compare continuous measurement data between two groups. Kruskal-Wallis test was used to compare continuous measurement data between multiple groups.Results:Plasma D-dimer levels in the ACLF [2 588.5 (1 142.8, 5 472.8) μg/L] ] and non-ACLF group [1 385.5 (612.0, 3 840.3) μg/L] had a significant difference ( P<0.001). ACLF-3 patients had significantly higher D-dimer levels than ACLF-1/2 patients (ACLF-3 vs. ACLF-1, P<0.001; ACLF-3 vs. ACLF-2, P<0.05). Patients who died at 28/90 days had significantly higher D-dimer levels than those whom survived ( P<0.001). There was a significant positive correlation between D-dimer level with prothrombin time (PT), international normalized ratio (INR), high-density lipoprotein C, as well as various prognostic scores (COSSH-ACLFs, CLIF-C ACLFs, CLIF-OFs, MELDs). AUROC of D-dimer in predicting the prognosis of ACLF patients at 28 days and 90 days was 0.751 (95% CI: 0.649-0.852) and 0.787 (95% CI: 0.695-0.878), respectively, which did not differ significantly compared with the predictive ability of other scores ( P<0.05), and similar results were confirmed by an external validation group of 125 cases. Conclusion:D-dimer level is significantly higher in patients with ACLF, so it is an independent predictor of prognosis at 28 and 90 days.

Objective: To analyze the impact of intergenerational care on child physical health, so as to provide references for promoting the overall development of children s health. Methods: Based on the 2016 national data of the Chinese Family Tracking Survey, descriptive statistics, Mann Whitney U test, Kruskal-Wallis H test and OLS regression analysis were used to explore the relationship between health status of 4 226 children aged 0-14 and intergenerational care. Results: OLS regression analysis showed that intergenerational care had a significant impact on physical health of preschool children (t=-2.11,P=0.04), but had no significant impact on the health of school-age children (t=-0.58,P=0.56). Annual family income, family population size, age and gender of caregivers had a significant impact on the health of preschool children (P<0.05).The self-rated health of caregivers and whether children participated in medical insurance had a significant impact on the health of all children (P<0.01). Conclusion Intergenerational care has a significant impact on the health status of preschool children, but has no impact on the health status of school age children. Attention should be paid to the health of caregivers, medical insurance condition and the impact of physical exercise on children’s health, as well as the health literacy improvement of child caregivers, and children’s medical insurance and welfare.

Objective:To analyze the clinical features of the recurrence of febrile seizures(FS), and observe the efficacy of levetiracetam(LEV)in preventing FS recurrence.Methods:We retrospectively analyzed the clinical data of 101 cases of FS recurrence who were admitted to the Department of Neurology of our hospital from May 2017 to May 2020, and collected the information of the recurrence after discharge and adverse effects of LEV application.Cox proportional hazards model regression was applied to explore the relationship between FS recurrence and LEV prophylaxis.Results:Among 101 cases of recurrent FS, the section of 18-60 months(63/101)composed the dominant proportion, of which the episode of 18-36 months(40/101)took the biggest recurrence rate.All 101 recurrent FS cases occurred within 24 hours of fever-beginning time, and 74.3%(75/101)occurred within 3 hours of fever onset.39.6% cases(40/101)were non-high febrile seizures, of which 30.0%(12/40)even had a temperature ≤38°C at the onset.Ninty-five cases of FS were included in the retrospective cohort study.Thirty-eight cases(4 lost to follow-up)were treated with LEV, while 57 cases(7 lost to follow-up)were not treated with any anticonvulsant drugs.The recurrence rate in the prophylactic group was 17.6%(6/34), compared with 44.0%(22/50)in the control group.The recurrence rate of the prophylactic group was statistically lower than that of the control group( χ2=6.325, P=0.012). Cox regression analysis was used to explore the relationship between FS recurrence and various factors, suggesting LEV prophylaxis( OR=0.325, 95% CI 0.129-0.821)and family history of FS( OR=3.060, 95% CI 1.427-6.560)affect the recurrence of FS.Then FS family history was stratified, LEV prophylaxis still statistically reduced the recurrence of FS( OR=0.316, 95% CI 0.124-0.802). Conclusion:The risk of recurrence increases significantly after 18 months of the age.Besides, FS recurrence is relatively common in the initial episode of fever and in the stage of low fever.For children at months of high probability of recurrence, prophylactic drugs should be used in the initial episode of fever and in the stage of low fever.LEV prophylaxis therapy is effective, with mild adverse reactions.