SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (M^pro) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Terminalia chebula Retz., as a potent non-peptidomimetic and non-covalent M^pro inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC₅₀ values below 2 μmol/L. Moreover, in vivo studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between M^pro domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the M^pro-CHLA complex, shrinking the substrate binding pocket of M^pro and inducing M^pro aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on M^pro and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition.

Objective:To establish the "1+3" management module of high-value consumables in Operation Room and verify its application, so as to provide new ideas for cost management of consumables in Operation Room.Methods:The Operating Room team of Shenzhen Hospital of Southern Medical University designed a "1+3" management module in 2022, where "1" referred to the management process of high-value consumables in Operation Room, and "3" referred to the precise management of consumables in Operation Room warehouse, the management of closed-loop use of Operation Room consumables and adverse event management of consumables. Surgeries using high-value consumables in the Thoracic Surgery Department, Gastrointestinal Surgery Department, and Urology Department of the hospital were selected as the research objects. The surgeries using conventional consumables from January to June 2022 were set as the control group, and the surgeries implementing the "1+3" management module from July to December 2022 were set as the observation group. The number of consumables received by the itinerant nurses before the operation and the number of high-value consumables returned after the operation were compared between the two groups. And the number of missed and error charges for high-value consumables in the two groups were counted and compared.Results:The number of consumables received before operation in the control group was higher than that in the observation group, and the difference was statistically significant ( P<0.05). The number of high-value consumables returned in the observation group was less than that in the control group, and the difference was statistically significant ( P<0.01). The proportion of missed charges for consumables in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.01), but there was no statistically significant difference in the proportion of incorrect charges between the two groups ( P>0.05) . Conclusions:The "1+3" management module for high-value consumables in Operation Room makes the process of receiving, returning, and charging high-value consumables clear, with traceable data, achieving refined management of high-value consumables in Operation Room, reducing the number of high-value consumables returned to the warehouse and reducing the proportion of missed consumables, which is conducive to effective cost control in Operation Room.

Renal cell carcinoma is one of the significant diseases endangering human health. Recent findings have shown that the human microbiome plays an important role in the occurrence and development of renal cell carcinoma, influencing its regression and treatment outcome. At present, microecological research on renal cell carcinoma are still in their initial stages, and their regulatory roles and specific mechanisms still need to be further explored. This article reviews the relationship between the human microbiome and renal cell carcinoma occurrence and development, as well as its role in diagnosis and therapies.

Accurate source localization of the epileptogenic zone (EZ) is the primary condition of surgical removal of EZ. The traditional localization results based on three-dimensional ball model or standard head model may cause errors. This study intended to localize the EZ by using the patient-specific head model and multi-dipole algorithms using spikes during sleep. Then the current density distribution on the cortex was computed and used to construct the phase transfer entropy functional connectivity network between different brain areas to obtain the localization of EZ. The experiment result showed that our improved methods could reach the accuracy of 89.27% and the number of implanted electrodes could be reduced by (19.34 ± 7.15)%. This work can not only improve the accuracy of EZ localization, but also reduce the additional injury and potential risk caused by preoperative examination and surgical operation, and provide a more intuitive and effective reference for neurosurgeons to make surgical plans.
Humans ; Scalp ; Brain Mapping/methods* ; Epilepsy/diagnosis* ; Electroencephalography/methods* ; Brain

Objective:To explore the role and mechanism of kidney brain protein (KIBRA) down-regulation in cognitive dysfunction caused by chronic cerebral hypoperfusion.Methods:Ninety male SPF grade Sprague Dawley (SD) rats were divided into four groups according to random number table: sham operation group ( n=15), chronic hypoperfusion group (2VO group, n=25), chronic hypoperfusion stereotaxic injection of AAV-KIBRA group (2VO+ AAV-KIBRA group, n=25), chronic hypoperfusion stereotaxic injection of AAV-Vector group (2VO+ AAV-vector group, n=25). Chronic cerebral hypoperfusion model was established by bilateral ligation of common carotid artery, and stereotactic injection of 2 μL AAV-KIBRA or AAV-vector was performed for 30 days.Morris water maze, in vitro electrophysiology, p21-activated kinase 3(PAK3) activity detection, Western blot, immunoprecipitation and Golgi staining were used to detect spatial learning and memory ability, long-term potentiation(LTP), KIBRA level expression, PAK3 activity changes and the distribution of dendritic spines.SPSS 16.0 statistical software was used for statistical data.One-way ANOVA was used to compare the differences between groups.LSD test was used to compare the significance of data differences between the two groups.Welch test was used for uneven variance. Results:After 1 month of chronic cerebral hypoperfusion, the level of KIBRA in the hippocampus of rats was detected by homogenate and Western blot, and it was found that the level of KIBRA in 2VO group was lower than that of sham group(73.49±4.12)% ( P<0.01). AAV-KIBRA injection in hippocampal CA1 region significantly up-regulated the level of KIBRA to (91.91±7.01)% over 2VO group ( P<0.01). Morris water maze test showed that the latency of the 2VO group(3rd-7th day trail data: (48.18±2.82)s, (43.45±2.27)s, (32.27±2.22)s, (26.55±2.37)s, (17.18±2.67)s) were significantly longer than those of the sham group((41.67±2.74)s, (32.58±2.57)s, (22.50±2.94)s, (16.91±2.39)s, (8.75±1.52)s) (all P<0.05), and the latencies of the 2VO+ AAV-KIBRA group 3rd-7th day trail data: (43.83±2.95)s, (35.25±2.15)s, (26.58±2.03)s, (19.92±2.17)s, (17.75±1.35)s) was significantly shorter than that of the 2VO group ((all P<0.01). The Morris water maze test with the platform removed showed that the latency of rats in the 2VO group to reach the platform region was significantly longer than that of the sham group, while the latency of rats in the 2VO+ AAV-KIBRA group to reach the platform region was significantly shorter than that in the 2VO group ( P<0.01). At the same time, the retention time and the crossing times in the platform region of 2VO group were less than those of the sham group ( P<0.01), but the retention time and the crossing times in the platform region of 2VO+ AAV-KIBRA group were significantly higher than those in the 2VO group ( P<0.01). The electrophysiological records of the brain slices showed that the relative excitatory postsynaptic field potential of 2VO group (1.43±7.43) was significantly lower than that of sham group (2.21±6.54) after high frequency stimulation, while the relative excitatory postsynaptic field potential of 2VO+ AAV-KIBRA group (1.90±8.15) was higher than that of 2VO group ( P<0.01). Immunoprecipitation in rat hippocampus revealed that PAK3 could be detected by Western blot assay when KIBRA was precipitated.The results showed that the relative enzyme activity of PAK3 in 2VO hippocampal tissue (0.64±0.04) was significantly lower than that in sham group (1.02±0.07), while the relative enzyme activity of PAK3 in 2VO+ AAV-KIBRA group (0.86±0.03) was significantly higher than that in 2VO group.Golgi staining showed that the density of dendritic spines in 2VO hippocampal neurons((6.85±0.43)/10 μm) was significantly lower than that in sham group((11.83±0.58)/10 μm), while the density of dendritic spines in 2VO+ AAV-KIBRA group((10.22±0.39)/10 μm) was significantly higher than that in 2VO group. Conclusion:The down-regulated of KIBRA after chronic cerebral hypoperfusion plays a key role in cognitive dysfunction and is also involved in the decrease of synaptic functional plasticity.The downregulation of KIBRA is involved in the structural plasticity of dendrites through the regulation of PAK3 activity.Therefore, KIBRA may be an important target for the prevention and treatment of cognitive function of chronic cerebral hypoperfusion.

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; COVID-19 ; Humans ; Hypertension/drug therapy* ; Renin-Angiotensin System ; Retrospective Studies

Objective:To explore the prevalence of hepatitis C virus (HCV) infection, influence factors and interaction on HCV infection in patients receiving methadone maintenance treatment (MMT) in Taiyuan.Methods:Between April-June 2019, three MMT clinics in Taiyuan were selected to conduct a face-to-face questionnaire survey among MMT patients to collect the information about their socio-demographic characteristics, drug use, MMT, sexual behavior and health status. Software EpiData 3.1 was used for real-time double entry to establish the database. Software SAS 9.4 was used to analyze the data, and χ 2 test was used for univariate analysis and logistic regression model was used for multivariate and interaction analyses. Results:A total of 903 subjects were surveyed among MMT patients, the male to female ratio of was 7.21∶1(743∶103), and the rate of HCV infection was 12.53% (106/846). After adjusting for the confounding factors, being women ( OR=1.936, 95% CI: 1.023-3.662), having sex with drug users ( OR=2.073, 95% CI: 1.110-3.871) and injection drug use ( OR=7.737, 95% CI: 4.614-12.973) might be the risk factors for HCV infection in patients receiving MMT. The results showed that there were multiplicative interactions among women, having sex with drug user and injection drug use on HCV infection. Conclusions:Being women, having sex with drug user and injection drug use were associated with higher risk for HCV infection in patients receiving MMT in Taiyuan. There were multiplication interactions between being women and having sex with drug user, being female and injection drug use, and having sex with drug use and injection drug use on HCV infection.

Collaborative development among medical practice, education and research is a strategic decision of the country in disciplinary development guided by the innovation-driven strategy. In October 2017, Beijing Hospitals Authority organized 18 tertiary hospitals with pediatrics discipline and founded a collaborative development center for pediatrics. This center operated in a model featuring both leadership of due authorities and autonomous administration. Two of the specialized pediatrics hospitals work as leading units, and existing high quality pediatrics resources of the member hospitals were pooled to establish an academics committee and an executive committee. A development system was established with disciplinary construction as the focus, collaborative development as the goal and horizontal collaboration as the means. It was designed to explore a new model featuring overall planning and standardized management of the discipline, building of a shared platform for clinical capacity development, joint development of continued medical education and talent cultivation, as well as diversified and multi-centered research and platform resources sharing. This model can effectively promote the overall development level of pediatrics in Beijing municipal hospitals.

Objective:To propose the application of recognizing bone species by touching blindly (ARBTB) and verify its application effect in human anatomy experimental courses.Methods:The study included experiment 1 and experiment 2, and the research objects were 60 students majoring in clinical medicine in Batch 2019 and 60 students majoring in preventive medicine in Batch 2018, respectively. The research objects in each experiment were randomized into mainstream teaching method group and ARBTB group, with 30 students in each group. In experiment 1, after students studying for the same hours, both of two groups carried out the same test, and then the average scores of the two groups were compared. In experiment 2, the average time spent by the two groups of students in osteology learning was compared.Results:In experiment 1, ARBTB group's average score of the test was significantly higher than that of the mainstream teaching group ( P<0.001). In experiment 2, the ARBTB group took much less time in osteology learning than the mainstream teaching group ( P<0.001). Conclusion:Compared with the mainstream teaching method, ARBTB is more effective in osteology learning, which is worth popularizing.

Objective To analyze the correlation between the clinical characteristics and the incidence of postoperative hepatic encephalopathy in patients with cirrhosis who received transjugular intrahepatic portosystemic shunt ( TIPS) . Methods The clinical data of 80 patients with liver cirrhosis hospitalized in the Fifth Medical Center of PLA General Hospital from March 2015 to March 2017 were retrospectively analyzed. The related factors of hepatic encephalopathy complications after TIPS treatment were analyzed. Results The cumulative incidence of hepatic encephalopathy was about 23. 75%(19／80) in one year after TIPS operation. Through single factor analysis and multi factor Logistic regression analysis,it was found that the two factors of preoperative platelet level and the location of tips blood shunt were closely related to the occurrence of hepatic encephalopathy after TIPS operation. The ROC curve suggested that the AUC of preoperative platelet level and the location of tips blood shunt were 0. 657 and 0. 668, respectively. The sensitivity and specificity of the former were 70. 0%,52. 6% and the cutoff value was 51 ×109／L, respectively, while those of the latter were 70. 5% and 63. 2%, respectively. Conclusion Preoperative platelets level＞51×109／L or shunting of the left branches of the portal vein may indicate a lower incidence of hepatic encephalopathy.