The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

OBJECTIVE To investigate the effects of peiminine B （PEI） on Streptococcus pneumoniae （SP）-induced alveolar epithelial cell injury by regulating the Ras-related C3 botulinum toxin substrate 1 in nucleus accumbens （Rac1）/protein kinase B （Akt）/nuclear factor κB （NF-κB） signaling pathway. METHODS Human alveolar epithelial cells （HPAEpiC） were taken and randomly divided into the Control group， SP group （1×108 cfu/mL SP bacterial solution）， low-， medium-， and high-concentration PEI groups （1×108 cfu/mL SP bacterial solution+0.05， 0.10， 0.20 mmol/L PEI）， and high-concentration PEI+Akt activator group （P-H+SC79 group， 1×108 cfu/mL SP bacterial solution+0.20 mmol/L PEI+10 μmol/L SC79）. Except for the Control group， the other groups of cells were treated with SP bacterial solution and/or corresponding drug solution. After 24 h of treatment， the levels of inflammatory factors （interleukin-6， -18， -1β） in the supernatant solution， the contents of oxidative stress indexes [lactate dehydrogenase （LDH）， reactive oxygen species （ROS） and superoxide dismutase （SOD）]， apoptosis rate， as well as the expressions of proliferation/apoptosis-related proteins [cyclin-dependent kinase 1 （CDK1）， B cell lymphoma-2 related X protein （Bax）] and pathway-related proteins （Rac1， Akt， phosphorylated Akt， NF-κB and phosphorylated NF-κB） were detected in each group. RESULTS Compared with the Control group， the levels of inflammatory factors in supernatant solution， LDH and ROS contents， apoptosis rate， the protein expressions of Bax and Rac1 and the phosphorylation levels of Akt and NF-κB in the SP group were significantly increased or up-regulated， while SOD content and the protein expression of CDK1 were significantly decreased or down-regulated （P＜0.05）. Compared with the SP group， the above indexes in PEI groups were significantly improved in a concentration-dependent manner （P＜0.05）. SC79 could significantly reverse the improvement effect of the high concentration of PEI （P＜0.05）. CONCLUSIONS PEI can alleviate SP-induced inflammation and oxidative stress damage of alveolar epithelial cells and inhibit apoptosis， which may be achieved by inhibiting Rac1/Akt/NF-κB signaling pathway.

Objective: To investigate the nutritional status and influencing factors among Tibetan and Mongolian children and adolescents aged 7-18 years in high-altitude regions, so as to provide evidence for early prevention and control of malnutrition in this population. Methods: From May to June 2022, a cluster sampling method was employed to recruit 1 019 Tibetan and Mongolian children and adolescents aged 7-18 years from two primary and secondary schools in Golmud City. Physical examinations, dietary frequency questionnaires, and physical activity assessments were conducted. Nutritional status was classified as obesity, combined overweight/obesity, underweight, or central obesity according to national standards including Screening for Overweight and Obesity among School-age Children and Adolescents, Screening Standard for Malnutrition of School-age Children and Adolescents, Blue Book on Obesity Prevention and Control in China. Chi-square tests, t-test and Logistic regression analyses were performed to identify factors associated with different nutritional statuses. Results: The detection rates of obesity, combined overweight/obesity, underweight, and central obesity were 8.0%, 18.1%, 5.2%, and 19.7%, respectively. The height of children and adolescents across all age groups was generally lower than the national standard values. Tibetan participants exhibited significantly lower height-for-age Z-scores (HAZ)(9-10, 13-17 years, Z =2.01, 2.78, 4.16, 3.38, 4.12, 3.63, 3.00) and BMI-for-age Z-scores (BAZ) compared to Mongolian participants ( Z =-2.95, -2.47, -2.31, -2.89, -2.14, -2.17)( P < 0.05 ). Multivariate Logistic regression revealed that Mongolian children and adolescents had higher risks of obesity ( OR =2.20) and combined overweight/obesity ( OR = 2.18 ) ( P <0.05). Additionally, insufficient moderate-to-vigorous physical activity (MVPA) was associated with an increased risk of central obesity ( OR =1.48, P <0.05), compared with children and adolescents who meet the standard of MVPA. Conclusions The rates of overweight and obesity among Tibetan and Mongolian children and adolescents in Golmud City are higher, influenced by multiple factors. Nutrition interventions and physical activity strategies tailored to ethnic characteristics should be implemented, with emphasis on promoting MVPA to improve nutritional outcomes in this population.

AIM: To investigate the mechanism of Hexue Mingmu Tablets(HXMMT)in improving diabetic retinopathy(DR)based on transcriptomics.METHODS: Zebrafish DR models were established by 3-day glucose induction(130 mmol/L)starting at 3 days post-fertilization(dpf). Larvae were randomized into four groups: control group(CG; aquaculture water), model group(MG; 130 mmol/L glucose), low-dose HXMMT treatment group(L-HX; 130 mmol/L glucose +7.5 mg/L HXMMT), and high-dose HXMMT treatment group(H-HX; 130 mmol/L glucose +75 mg/L HXMMT), with a 3-day intervention period until 6 dpf. The area and length of eyes, and body length of zebrafish were observed by stereomicroscopy, retinal morphology was observed by hematoxylin-eosin staining(HE), and retinal vessel diameter was observed under fluorescence microscope. Differentially expressed genes(DEGs)were identified by RNA-sequencing(RNA-seq)technology to further elucidate the molecular mechanism of HXMMT in improving DR in zebrafish, and the sequencing accuracy was validated through quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS: HE staining demonstrated that the intervention with HXMMT significantly improved the disordered cell arrangement, widened gaps, and thickened inner nuclear layer(INL)in ganglion cell layer GCL); retinal vascular diameter quantification revealed that the retinal vessel diameter of the MG significantly increased compared with the CG, and it was significantly changed after the intervention of HXMMT, with significant efficacy in the H-HX(P<0.05); transcriptomics profiling identified 1 470 reversed DEGs, predominantly enriched in the AMPK signaling pathway, FoxO signaling pathway, retinal developmental processes, and tight junction regulation. Technical validation confirmed strong correlation between qRT-PCR and RNA-seq data(R2=0.8571, P<0.05).CONCLUSION: HXMMT may improve retinal vascular microcirculation disorders in DR by regulating core targets including vsx1, pde6c, arr3a, plk1, fbp1b, foxo1a, pcna, and cdk1, as well as synergistically modulating processes such as retinal development in camera-type eyes, visual perception, microtubule cytoskeletal organization, tight junctions, and the AMPK signaling pathway, Foxo signaling pathway.

AIM: To compare the effectiveness of foldable capsular body(FCB)with traditional scleral buckling(SB)in the treatment of experimental retinal detachment animal models.METHODS: After successfully establishing rhegmatogenous retinal detachment(RRD)animal models, 24 New Zealand white rabbits were randomly divided into three groups(RRD models group, SB group, and FCB group), with 8 rabbits in each group. The FCB and SB groups underwent SB and FCB surgeries for the RRD animal models, while the RRD models group only consists of RRD models without any surgical intervention during the follow-up period. The follow-up duration was 3 mo. Wide-field neonatal fundus imaging system and ophthalmic B-ultrasound were used to assess the fundus conditions before and after surgery. The Icare® TONOVET Plus tonometer was utilized to evaluate intraocular pressure changes before and after surgery. The Eaton and Draize scoring systems were selected to monitor postoperative inflammatory reactions.RESULTS: The retinal reattachment rates in the FCB and SB groups were 87.5% and 75.0%, respectively, with no statistically significant difference between the groups(P>0.05). The intraocular pressure in both the FCB and SB groups increased postoperatively compared to preoperative levels(P<0.01), and there were no significant differences in intraocular pressure at any time points during the follow-up period between the groups(P>0.05). The intraocular pressure in the RRD models group remained at a low level throughout the follow-up period. The average surgical time for the FCB group was 16.87±2.29 min, which was shorter than 46.25±4.74 min in the SB group(t=-15.166, P<0.001). According to the Eaton and Draize scoring systems, the FCB group had lower grades of conjunctival hyperemia and edema in the early postoperative period compared to the SB group, indicating milder inflammatory reactions(P<0.05).CONCLUSION: Both FCB and SB are effective in treating experimental RRD. Compared to SB, FCB is simpler to operate, and also has a shorter surgical time and milder postoperative inflammatory reactions.

Objective: To analyze the timeliness of antir-etroviral therapy (ART) and its influencing factors among newly reported HIV/AIDS cases in Wenzhou City, Zhejiang Province from 2016 to 2023, so as to provide a reference for improving the ART effect of HIV/AIDS cases. Methods: Newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were selected as the research subjects. Demographic information, the situation of the first CD4+ T lymphocyte (CD4 cell) test, baseline CD4 cell count, and ART situation were collected through the Chinese Disease Prevention and Control Information System. The timely rate of ART was analyzed, and the influencing factors for timely ART among HIV/AIDS cases were analyzed using a multivariable logistic regression model. Results: A total of 4 500 newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were included, among which 3 679 were males, accounting for 81.76%, and 821 were females, accounting for 18.24%. The median age was 46.24 (interquartile range, 26.23) years. Among these cases, 3 606 received timely ART, with a timely rate of 80.13%. The timely rate of ART increased from 57.54% in 2016 to 91.97% in 2023 (P<0.05). Multivariable logistic regression analysis showed that unmarried/divorced/widowed (OR=0.769, 95%CI: 0.641-0.922), detainees (OR=0.492, 95%CI: 0.269-0.900), untimely first CD4 cell test (OR=0.278, 95%CI: 0.234-0.330), baseline CD4 cell count ≥200 cells/µL (OR=0.709, 95%CI: 0.595-0.843) or undetected (OR=0.131, 95%CI: 0.080-0.213) were associated with a lower timeliness for ART among HIV/AIDS cases. Conclusion From 2016 to 2023, the timely rate of ART among newly reported HIV/AIDS cases in Wenzhou City showed an upward trend, which was mainly affected by marital status, case source, timeliness of the first CD4 cell test, and baseline CD4 cell count.

OBJECTIVE To explore the improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis （RA） rats by regulating neutrophil extracellular traps （NETs）. METHODS Establishment of rat RA model using bovine type Ⅱ collagen and Freund’s complete adjuvant. The model rats were randomly divided into model group and low-dose， middle-dose and high-dose groups （55， 110， 220 mg/kg） of petroleum ether extract of S. divaricata； the normal group without modeling was also established， with 10 rats in each group. Each group was given corresponding drugs or constant volume of 2% Tween-80 solution intragastrically， once a day， for consecutive 28 days. The toe swelling degree in rats was observed， and the arthritis index （AI） was scored. The serum levels of interleukin-1β （IL-1β）， IL-10， IL-17， tumor necrosis factor-α （TNF-α）， 25-hydroxyvitamin D3 [25（OH）D3]， myeloperoxidase （MPO）， neutrophil elastase （NE） and NETs in rats were detected. The histopathological changes in ankle joint were observed. The expression of citrullinated histone H3 （CitH3） in ankle joint as well as the expressions of cytochrome P450 24A1 （CYP24A1）， cytochrome P450 27B1 （CYP27B1），vitamin D receptor （VDR） and peptidyl arginine deiminase 4 疾病。E-mail：zhongyao626@126.com （PAD4） in synovium were all determined. RESULTS Compared with the model group， the toe swelling degree and AI score in the middle-dose and high-dose groups of petroleum ether extract of S. divaricata decreased significantly from day 14 to day 28 after administration （P＜0.05 or P＜0.01）. The serum levels of IL-1β， IL-17， TNF-α， MPO， NE and NETs decreased significantly， while the levels of IL-10 and 25（OH）D3 increased significantly （P＜0.05 or P＜0.01）. The widened ankle joint space and the improved structure were found； the expression of CitH3 in ankle joint， and the expressions of CYP24A1 and PAD4 in synovium were down-regulated significantly， while the expressions of CYP27B1 and VDR were up-regulated significantly in synovium （P＜0.05 or P＜0.01）. CONCLUSIONS The petroleum ether extract of S. divaricata may inhibit the production of NETs and improve the symptoms of RA by regulating the vitamin D system.

ObjectiveTo determine the optimal dose of Dachengqi Decoction （大承气汤， DCQD） for the treatment of acute intestinal obstruction （AIO） through a randomized， double-blind， dosage parallel controlled， multi-center clinical trial， and to providee evidence support for the reasonable dosage of DCQD in clinical practice. MethodsBased on the commonly used clinical dose of DCQD， three different groups were set up， including low-dose group which used Dahuang （Radix et Rhizoma Rhei） 12 g， Houpo （Cortex Magnoliae Officinalis） 9 g， Zhishi （Fructus Aurantii Immaturus） 9 g， and Mangxiao （Natrii Sulfas） 4.5 g， medium-dose group using Dahuang 36 g， Houpo 27 g， Zhishi 27 g， Mangxiao 13.5 g， and high-dose group using Dahuang 60 g， Houp0 45 g， Zhishi 45 g and Mangxiao 22.5 g. Initially， 149 AIO patients with Yangming （阳明） bowel excess syndrome were randomly assigned to three groups using a stratified randomization method， and both the patients and the doctors were blinded. In addition to conventional western medicine treatment， each group was given 12 bags of granules made from the raw herbs of DCQD at different doses， taken orally or injected through a gastric catheter once every 6 hours， 3 bags each time， for 3 consecutive days. After treatment， the indicators of the three groups of patients with primary AIO and non-primary AIO were evaluated respectively， and the full analysis set （FAS） and per-protocol set （PPS） were used for analysis. The primary outcomes were the time to recover voluntary bowel movements and voluntary flatulence. The secondary outcomes were the ideal rate of spontaneous defecation and the ideal rate of spontaneous flatus. The occurrence of adverse events during the study was recorded and analyzed using the safety analysis set （SS）. ResultsA total of 91 patients with primary AIO and 58 patients with non-primary AIO were included in the FAS and SS analysis， while 80 primary AIO patients and 56 non-primary AIO patients were included in the PPS analysis. Both FAS and PPS analysis showed significant differences in the time to recover voluntary bowel movements and voluntary flatulence among primary AIO patients in different dose groups of DCQD （P＜0.01）， and the high- and medium-dose groups assumed less time than the low-dose group （P＜0.05）. There was no statistically significant difference in the ideal rate of spontaneous defecation and spontaneous flatus among the three groups （P＞0.05）. And consistent results were seen in the non-primary AIO patients among the three groups. Five adverse events occurred in primary AIO patients （3 in the low-dose group， 1 in the medium-dose group， and 1 in the high-dose group）， mainly manifested as abdominal distension and abdominal pain， and there was no statistically significant difference in the incidence of adverse events （P＞0.05）. No adverse events occurred in patients with non-primary AIO. ConclusionDCQD， as an effective treatment for patients with AIO， is commonly used at a medium dose for patients with primary AIO and at a high dose for patients with non-primary AIO. The therapeutic advantage is mainly reflected in the shorter time to recover spontaneous defecation and spontaneous flatulence and the improvement of intestinal function.

Objective To study the serotype, drug resistance, and molecular typing characteristics of Salmonella enteritidis strains isolated from patients with diarrhea in Xiangyang City. Methods Serotyping, drug sensitivity test, pulsed field gel electrophoresis (PFGE) typing, and whole genome sequencing were carried out on Salmonella enteritidis strains isolated from diarrhea patients from 2019 to 2020. Results From the drug susceptibility test , Salmonella enteritidis in this region showed varying degrees of drug resistance, with 94.7% of Salmonella enteritidis strains being multidrug-resistant. The PFGE electrophoretogram of Salmonella enteritidis showed that 19 strains could be divided into 6 PFGE types by cluster analysis, among which 12 strains belonged to the epidemic dominant type. MLST typing showed that all 15 strains were ST11 type, carrying multiple drug resistance genes (mdsA, mdsB, mdsC, gols, and sdiA) and mdtK gene, and all carried various invasiveness-related virulence genes. However, there were slight differences in virulence genes related to the secretion system of the pathogenic island among the different strains. The phylogenetic tree analysis of the system evolution showed that 15 strains could be divided into 2 different evolutionary branches. Conclusion The situation of multidrug resistance in Salmonella enteritidis in Xiangyang is serious, with dominant PFGE types and ST types, and it carries multiple drug resistance genes and various invasiveness-related virulence genes.