Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

【Objective】 To analyze the effects of different fortified feeding methods on nutritional metabolism and growth rate of preterm very low birth weight infants (VLBWI), in order to provide new clues for improving the prognosis of the preterm infants. 【Methods】 A total of 115 cases of premature VLBWI admitted to Department of Neonatology, The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2020 were included in this study, and were divided into fortified breastfeeding group (HFM group), mixed feeding group, and premature formula feeding group (PF group) based on their feeding methods. The effects of different feeding methods on the nutritional metabolism and growth rate of premature VLBWI were analyzed. 【Results】 1) The hospitalization time of infants in the HFM group was shorter than that in PF group and mixed feeding group (t=7.185, 6.924, P<0.05). 2) The proportion of necrotizing enterocolitis (NEC) in the HFM group during hospitalization was lower than that in the PF group (P<0.05); the proportions of late onset septicemia(LOS) and extra uterine growth restriction(EUGR) in the HFM group during hospitalization were lower than those in the PF group (χ²=5.030, 4.147, P<0.05); the proportion of LOS was lower than that of the mixed feeding group(χ²=6.589, P<0.05). 3) During hospitalization, the proportions of abdominal distension, bloody stools and increased eosinophils in the HFM group were lower than those in the PF group (P<0.05), which in mixed feeding group was lower than those in PF group (Fisher exact test, P<0.05). 4) At discharge, the weight and length growth rate of the HFM group were higher than those of the mixed feeding group (t=3.722, 0.425, P<0.001) and the PF group (t =6.015, 0.496, P< 0.001). 【Conclusion】 Fortified breastfeeding can more effectively increase the growth rate of VLBWI in premature infants, improve nutritional metabolism, reduce complications and adverse feeding reactions related to premature infants, and is safer and more effective.

The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.

Objective:To investigate the necessity of adaptive re-planning during radiotherapy for nasopharyngeal carcinoma (NPC) and its impact on dose improvement.Methods:Clinical data of 89 NPC patients admitted to Sun Yat-sen University Cancer Center from July 2014 to December 2017 were retrospectively analyzed. All patients received 25+7 rounds of adaptive re-planning during radiotherapy. Plan-A was defined as the initial CT scan-based 25-fraction radiotherapy plan, while plan-B was defined as the re-planned 7-fraction radiotherapy plan based on a subsequent CT scan. The changes in the target and parotid gland volumes were compared between plan-A and plan-B. Plan-I was a one-time simulation of plan-A extended to 32 fraction radiotherapy plan, and plan-II was generated through registration and fusion of the plan-A and plan-B for adaptive re-planning. The differences in dose metrics, homogeneity index (HI), conformity index (CI), and dose to organs at risk (OAR) were compared between plan-I and plan-II. Statistical analysis was performed by using paired t-test. Results:Compared with plan-A, the gross tumor volume of massive bleeding lesions (GTV nx) and parotid gland volume of plan-B were decreased by 13.14% and 11.12%, respectively (both P<0.001). While planning clinical target volume of metastatic lymph nodes (PCTV nd) of plan-B was increased by 7.75%( P<0.001). There were significant changes in the lymph nodes of plan-A and plan-B. The D mean, D 5%, D 95% of massive bleeding lesions planning target volume (PTV nx) and D 5% of high risk planning target volume (PTV1) in plan-II were all significantly higher than those in plan-I (all P<0.05). The CI of PTV nx and PTV1 in plan-II was closer to 1 than that in plan-I. In all assessed OAR, the D mean, D 50%, and D max of plan-II were significantly lower than those of plan-I (all P<0.05). Conclusions:During radiotherapy, NPC patients may experience varying degrees of primary tumor shrinkage, parotid gland atrophy, and lymph node changes. It is necessary to deliver re-planning and significantly improve the dose of target areas and OAR.

ObjectiveTo investigate the therapeutic effect of Qinggongtang in regulating Glu/GABA metabolic balance and the mechanism of its anxiolytic effect on rat models of anxiety. MethodFifty-four rats were randomly divided into normal， model， diazepam （0.225 mg·kg^-1）， and low-dose， medium-dose， and high-dose groups of Qinggongtang （5.085， 10.17， 20.34 g·kg^-1）， with nine rats in each group. Except for the normal group， the other groups were subjected to indeterminate vacutainer stress and chronic restraint stress for 12 days to prepare the anxiety model. On the 3^rd day of the stress， 10 days of corresponding drug intervention was started. At the end of the drug treatment， the anxiety level of rats in each group was evaluated by the elevated cross maze experiment （EPM） and the light and dark box experiment （LDB）， and the effect of Qinggongtang on the anxiety behavior of rats was preliminarily analyzed. The levels of Glu and GABA in the amygdala tissue of the rats were detected by enzyme linked immunosorbent assay （ELISA）， and the changes in the synaptic ultrastructure of the amygdala of the rats in each group were observed by electron microscopy. The mRNA expression of glutamic acid decarboxylase （GAD65 and GAD67）， glutamine synthetase （GS）， and glutamate transporter-1 （GLT-1） in the amygdala were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and their protein expression was detected by Western blot. ResultCompared with those in the normal group， rats in the model group showed an obvious anxiety state and dull yellow and lusterless fur. They were irritable， easy to anger， and preferred to curl up in the corner. The number of times the EPM entered the open arm and the residence time in the open arm were significantly reduced （P<0.01）， and the residence time in the open box and the number of times the LDB went through the box were significantly reduced （P<0.01）. The content of Glu in the amygdala was increased （P<0.01）， and the content of GABA was reduced （P<0.01）. The value of Glu/GAB was elevated （P<0.01）， and the number of synaptic and pre-synaptic membrane vesicles in the amygdala was decreased. Sparse dense material in the post-synaptic membrane， increased synaptic gap， slightly disrupted internal structure， and decreased mRNA and protein expressions of GAD65， GAD67， GS， and GLT-1 in the amygdala were observed （P<0.01）. Compared with those in the model group， rats in the medium-dose and high-dose groups of Qinggongtang and the diazepam group had bright fur， sensitive reactions， and more active behavior. The number of times EPM entered the open arm and the residence time in the open arm increased significantly （P<0.01）， and the residence time in the open box and the number of times the LDB went through the box increased significantly （P<0.01）. The content of Glu in all-dose groups of Qinggongtang and the diazepam group decreased （P<0.05， P<0.01）， while GABA content increased （P<0.05， P<0.01）. The value of Glu/GABA decreased （P<0.01）， and the internal and external synaptic structure of each groups of Qinggongtang and the diazepam group was more complete. Synapses and vesicles were numerous， and the synaptic gap was more clearly defined. The efficacy of the high-dose group of Qinggongtang and the diazepam group was the best， and the mRNA and protein expressions of GAD65， GAD67， GS， and GLT-1 in the amygdala were increased in the high-dose group of Qinggongtang and diazepam group （P<0.05， P<0.01）. ConclusionQinggongtang can improve synaptic plasticity and affect the expression of GAD65， GAD67， GS， and GLT-1 in the amygdala of rats to regulate Glu/GABA metabolic balance and thus exert anxiolytic effects.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

ObjectiveTo analyze the long-term trends of the disease burden of diabetes attributed to metabolic factors in China from 1990 to 2019, and provide scientific recommendations for diabetes prevention and control in China. MethodsDescriptive analysis was conducted on the disease burden data of diabetes attributed to metabolic factors in China from 1990 to 2019, obtained from GBD 2019, encompassing death form diabetes, disability-adjusted life years (DALY), years of life lost (YLL), and years lived with disability (YLD). Joinpoint regression models were employed to analyze the long-term trends in mortality and DALY rates. Furthermore, the study examined the impact of two metabolic risk factors, high fasting plasma glucose (FPG) levels and high body mass index (BMI) levels, on the disease burden of diabetes. ResultsFrom 1990 to 2019, the overall standardized mortality and DALY rates attributed to metabolic factors for diabetes in the general population in China showed an upward trend, with both average annual percent changes (AAPCs) of 0.1% in the total population. The trend was upward in males with AAPCs of 0.9% and 0.6%, while it was downward in females with AAPCs of -0.4% and -0.3%. As age increased, the disease burden of diabetes attributed to metabolic factors showed an upward trend, with high FPG and high BMI ranking as the top two attributing risk factors. The disease burden of diabetes attributed to metabolic factors was higher in Chinese males than females. ConclusionThe disease burden of diabetes attributed to metabolic factors is increasing among the overall population and particularly among males, while the burden for female is declining. There is a need to increase intervention efforts for males aged 65 and above, provide scientific guidance on residents’ diet and lifestyle habits, and control blood glucose and body weight.

Objective·To investigate the relation between urinary excretion of protein-bound uremic toxins(PBUTs)and upper urinary tract calculus.Methods·Residents aged 18?80 years in the community of Haitou,Danzhou city in Hainan Province were recruited.Basic information and diet for the last 3 d of the subjects were recorded.Their fasting sera and 24-hour urine samples were collected,and they also underwent ultrasound examination of kidneys and ureters.The subjects with upper urinary calculi detected by ultrasound or a clear history of upper urinary calculi were selected as the calculus group,and the others as the non-calculus group.The biochemical indicators related to the formation of calculus in blood and urine were detected,and the levels of PBUTs,including indoxyl sufate(IS),indole-3-acetic acid(IAA),and p-cresol sulfate(PCS)in blood and urine,as well as oxalic acid and citric acid in urine were detected by high-performance liquid chromatography.The related factors of upper urinary tract calculus formation were analyzed by multivariate Logistic regression.The correlations of urine PBUTs with urine uric acid,oxalic acid,and citric acid were analyzed by Spearman correlation test.Results·A total of 117 participants were screened out with 54 people in the calculus group and 63 people in the non-calculus group.There were no significant differences between the two groups in terms of gender,age,serum indicators,and prevalence of complications such as hypertension,diabetes,and hyperuricemia/gout.The 24-hour urine pH,calcium,uric acid,and chlorine in the calculus group were significantly higher than those in the non-calculus group(all P<0.05),while IS was significantly lower than that in the non-calculus group(P<0.05).Multivariate Logistic regression analysis showed that urinary IS(OR=0.929,95%CI 0.875?0.986,P=0.016)was related to the calculus formation independently,in addition to urinary calcium.The Spearman correlation analysis results showed that the levels of IAA(r=0.420,P=0.000)and PCS(r=0.307,P=0.001)in 24-hour urine were positively correlated with oxalic acid,PCS was positively correlated with uric acid(r=0.297,P=0.002),and IS was positively correlated with citric acid(r=0.289,P=0.002).Conclusion·In the population,a decrease in urinary excretion of IS may be an independent risk factor for the formation of upper urinary tract calculus,and PBUTs levels are correlated with levels of uric acid,oxalic acid,and citric acid.

Objective:Exploring the effect of radiofrequency ablation treatment to restore sinus rhythm on the improvement of functional mitral regurgitation (FMR) and cardiac structure in patients with atrial fibrillation combined with moderate or severe FMR, compared with drug therapy alone.Methods:This retrospective cohort study consecutively enrolled patients diagnosed with persistent atrial fibrillation and moderate or severe FMR who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2021. Forty-eight patients who were treated with radiofrequency ablation and maintained sinus rhythm were enrolled in the ablation group, and 63 patients who were treated with medication alone during the same period were in the medicine group. Patients in the ablation group and medicine group were matched in a 1∶1 ratio using a propensity score, and 41 patients were finally included in each of the 2 groups. All patients reexamined echocardiography after 3-month of treatment. The proportion of patients with FMR improvement and the differences in changes of cardiac structural and functional parameters were compared between groups.Results:After propensity score matching, the ablation group was aged (69.3±7.1) years with 21 males (51.2%) and the medicine group was aged (71.3±9.4) years with 21 males (51.2%). The echocardiography after 3-month of treatment showed the rate of FMR improvement was significantly higher in the ablation group than in the medicine group (19 (46.3%) vs. 33 (80.5%), P<0.001), and patients in the ablation group showed a significant decrease in FMR extent (Δmitral regurgitation area: (-1.30±2.64) cm 2 vs. (-3.55±2.50) cm 2, P<0.001), left atrial size (Δleft atrial diameter: (-0.17±3.78) mm vs. (-2.46±4.01) mm, P=0.009) and E/e′ (ΔE/e′:-2.54±7.34 vs.-6.34±7.08, P=0.021) compared with the medicine group. There was also a significant decrease in left ventricular size (Δleft ventricular end diastolic diameter: (-3.12±6.62) mm vs. (-0.73±3.62) mm, P=0.046) and significant increase in left ventricular ejection fraction (Δleft ventricular ejection fraction: (2.73±9.69) % vs. (-0.93±5.41) %, P=0.038) in ablation group. Conclusion:Performing radiofrequency ablation to restore sinus rhythm can effectively reduce the severity of mitral regurgitation and improve left atrial and left ventricular remodeling and cardiac function in patients with atrial fibrillation and FMR.