ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

Objective To investigate the epidemic characteristics and factors influencing mortality in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patients in heilongjiang region. Methods The clinical data of 712 HIV-infected patients attending our hospital from January 2019 to December 2023 were analyzed retrospectively. The HCV infections were detected by ELISA, and epidemic characteristics of HIV/HCV co-infected patients were analyzed . Co-infected patients (n=116) were classified into survival group (n=90) and death group (n=26) according to the follow-up results, and risk factors for the mortality of HIV/HCV co-infected patients were identified. Results The prevalence of HIV/HCV co-infection was 16.29%, and the prevalence was the highest in 30-50 age group, accounting for 25.47%. There was no significant difference in co-infection rates by gender and marital status (P>0.05). The co-infection rate was the highest among farmers (26.85%) by occupation and among intravenous drug users (61.90%) by route of infection. No statistical difference was found in gender, marital status, and occupational status between survival group and death group (P>0.05), whereas statistical difference was found in age at diagnosis of HIV infection, route of infection, antiretroviral treatment, percentage of CD4+T lymphocytes, and interval between diagnosis and initiation of treatment between two groups (P<0.05). Multivariate Logistic regression analysis denoted that age at diagnosis of HIV infection (OR=1.827, 95% CI: 1.263-2.722), route of infection (OR=1.796, 95% CI: 1.248-2.503), antiretroviral treatment (OR=1.724, 95% CI: 1.202-2.367), percentage of CD4+T lymphocytes (OR=2.536, 95% CI: 1.776-3.739), and the time interval between diagnosis and initiation of treatment (OR=1.953, 95% CI: 1.431-2.952) were all associated with the risk of mortality in co-infected patients (P<0.05). Conclusion The overall prevalence of HIV/HCV co-infection is 16.29% in heilongjiang region . In order to reduce the mortality rate of superinfection , we should focus on patients who are ≥ 40 years old, intravenous drug use , no antiviral therapy , low CD4+ T lymphocyte levels for the first time , and have a long interval between diagnosis and initiation of treatment.

Objective:To investigate the effects of Xiaomudan Granules on PERK/eIF2α/ATF4 pathway and lipid metabolism in NAFLD mice.Methods:Totally 60 mice were divided into a normal group of 10 mice and a high-fat diet group of 50 mice. The high-fat diet group was given a high-fat diet to establish a NAFLD mouse model. The high-fat feed group was divided into model group, metformin group, and Xiaomudan Granules low-, medium-, and high-dosage groups according to the random number table method. Xiaomudan Granules low-, medium-, and high-dosage groups were orally administered with concentrated Xiaomudan Granules at dosages of 11.7, 23.4, and 46.8 g/kg, respectively. The metformin group was orally administered with metformin solution at a dose of 0.2 g/kg, while the normal group and model group were orally administered with distilled water of equal volume once a day for 8 consecutive weeks. The liver oil red O staining of mice was observed in each group. The protein expressions of p-PERK, p-eIF2α, ATF4, C/EBP homologous protein (CHOP), CCAAT enhancer binding protein alpha (C/EBPα), C/EBPβ, and steroid regulatory element binding protein 2 (SREBP2) were detected by Western blot. Fluorescence quantitative PCR was used to detect the mRNA expressions of ATF4, CHOP, C/EBPα, C/EBPβ, and SREBP2.Results:The liver tissue structure and steatosis of mice were improved in Xiaomudan Granules groups. Compared with the model group, the expressions of p-PERK/PERK, ATF4, C/EBPα, C/EBPβ, and SREBP2 proteins decreased in Xiaomudan Granules groups and the metformin group ( P<0.01 or P<0.05). The expressions of p-eIF2α/eIF2α and CHOP proteins decreased in the Xiaomudan Granules medium- and high-dosage groups and the metformin group ( P<0.01); compared with the model group, the levels of ATF4, CHOP, C/EBPα, and C/EBPβ mRNA in Xiaomudan Granules groups and the metformin group decreased ( P<0.01), while the levels of SREBP2 mRNA in the Xiaomudan Granules medium- and high-dosage groups and the metformin group decreased ( P<0.01). Conclusion:Xiaomudan Granules may improve liver lipid metabolism and reduce liver fat deposition in NAFLD mice by regulating the PERK/eIF2α/ATF4 pathway.

Myasthenia gravis(MG)is an autoimmune disease characterized primarily by skeletal muscle weakness and,in severe cases,respiratory involvement.Western medical treatment predominantly relies on immunosuppressants,but long-term administration often leads to notable side effects.In contrast,traditional Chinese medicine(TCM)offers the advantage of multi-target interventions.However,the pathogenesis of MG has not been fully elucidated,and the establishment of animal models that accurately reflect the clinical characteristics of both Chinese and Western medicine is essential for mechanism research and new drug development.This paper systematically reviews the etiology and pathogenesis,diagnostic criteria,and progress of animal model research for MG from both Chinese and Western medicine perspectives.In Western medicine,the pathogenesis of MG is closely related to genetic susceptibility,environmental factors,and autoantibody-mediated postsynaptic membrane damage.In TCM,MG is classified under the category of"flaccidity syndrome",attributed to congenital deficiencies and acquired malnourishment.Western diagnostic criteria involve a combination of clinical symptoms,fatigue testing,serum antibody assays,and electrophysiological evaluation.In contrast,TCM diagnosis emphasizes the integration of primary and secondary symptoms with tongue and pulse pattern differentiation.Currently available animal models mainly include experimental autoimmune myasthenia gravis(EAMG)and passive transfer myasthenia gravis(PTMG).The Toredo acetylcholine receptor(AChR)induced EAMG model aligns well with Western diagnostic criteria,but poorly matches secondary symptoms in TCM.The synthetic AChR peptide model is widely used,but shows low conformity with TCM syndromes.Models induced by muscle-specific tyrosine kinase(MuSK),low-density lipoprotein receptor-related protein 4(LRP4),and transgenic models demonstrate high innovation but exhibit low clinical conformity.Evaluation of these models requires integration of behavioral,electrophysiological,and immunological indicators.However,a systematic framework for modelling TCM syndromes is still lacking.Future research should integrate TCM-based etiological modelling methods with the Western pathological mechanisms to construct disease-syndrome combination models.Additionally,it is crucial to establish a TCM syndrome evaluation system based on"validation by prescription",as well as to improve the scientific rigor and practicality of animal models by the incorporation of emerging technologies.This review provides a theoretical foundation for optimizing MG animal model design,advancing the research on the combination of Chinese and Western medicine,and supporting efficacy assessment and mechanism exploration of Chinese herbal prescriptions.

Objective:To elucidate the role of solute carrier protein 7,family member 11(SLC7A11)/Glutathione peroxi-dase 4(glutathione peroxidase 4,GPx4)regulated ferroptosis pathway in the improvement of sarcopenia through aerobic exercise,and to identify a new target for the prevention and treatment of sarcopenia with exercise.Method:Twenty 52-week-old Specific pathogen Free(SPF)C57BL/6 male mice were randomly divided into the old control group(OC)and the old exercise group(OE).There were 10 mice in each group.Following one week of adaptive exercise,moderate-intensity exercise with incremental load was implemented as follows:14 m/min at 1-2 weeks,15 m/min at 3-4 weeks,16m/min at 5-10weeks,17m/min at 11-16weeks,60min/d,all with a slope of 0°.Gastrocnemius was harvested for ultrathin electron microscope sections.The levels of Glutathione(GSH),muscle glycogen and non-heme iron(non-heme iron)were measured by spectro-photometer.The serum ferritin(SF),mitochondrial 8-hydroxy-2 deoxyguanosine(8-OHdG)and 4-Hydroxynone-na(4-HNE)were measured by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of iron metabolism-related proteins,such as GPx4,SLC7A11,ferroportin 1(FPN1)and ferri-tin heavy chain 1(FTH1)in gastrocnemius muscle.Result:①Compared with OC,the wet weights of quadriceps femoris and gastrocnemius in OE were signifi-cantly increased(P＜0.01).In the exercise group,mitochondrial cristae arranged neatly and densely,and the light and dark bands of myofilaments were clear.In the aged control group,the mitochondrial cristae of gas-trocnemius muscle were disrupted,vacuolated or pyknotic,showing typical features of ferroptosis.② The SF and the iron content of gastrocnemius muscle were decreased in OE(P＜0.01).③ The levels of 4-HNE and 8-OHdG in gastrocnemius muscle of OE were significantly lower than those of OC(P＜0.01).The GSH content in gastrocnemius of OE was significantly higher than that of OC(P＜0.01).④ The expressions of SLC7A11,GPx4,FPN1 and FTH1 in gastrocnemius muscle of OE were significantly higher than those of OC(P＜0.01).Conclusion:Moderate aerobic exercise can prevent age-related sarcopenia by activating the SLC7A11/GPx4 pathway and inhibiting mitochondrial ferroptosis.

Objective To observe the clinical efficacy of Lingnan fire needle therapy combined with conventional western medicine in the treatment of mild to moderate uterine prolapse.Methods A total of 96 patients diagnosed with mild to moderate uterine prolapse in the outpatient and inpatient departments of Dongguan Humen Traditional Chinese Medicine Hospital from January 2023 to January 2024 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 48 cases in each group.Both groups received health education,and the control group received conventional western medicine treatment.The observation group received Lingnan fire needle therapy in addition to the control group's treatment.The treatment course consisted of 12 sessions,with one course completed.After treatment,the clinical efficacy of the two groups was evaluated.Changes in TCM syndrome scores,pelvic floor muscle strength,and ultrasound imaging characteristics were observed before and after treatment.The serum levels of osteopontin(OPN),connective tissue growth factor(CTGF),and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1(MMP-9/TIMP-1)were compared before and after treatment.The safety and incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate in the observation group was 97.92%(47/48),while it was 77.08%(37/48)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the TCM syndrome scores and total scores in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the pelvic floor muscle strength and ultrasound imaging characteristics in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these aspects compared to the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the serum levels of OPN,CTGF,and MMP-9/TIMP-1 in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Lingnan fire needle therapy combined with conventional western medicine can significantly improve symptoms and pelvic floor muscle strength in patients with mild to moderate uterine prolapse,with notable efficacy and high safety.The mechanism may be related to the regulation of OPN,CTGF,and MMP-9/TIMP-1 levels.

Objective:This study aims to investigate the feasibility and safety of implanting leadless pacemakers in the low septum and its impact on cardiac electrical synchronization.Methods:A total of 36 patients who received leadless pacemaker implantation at Fuwai Central China Cardiovascular Hospital from January 2021 to August 2023 were included in this study.According to implantation sites of leadless pacemakers,patients were divided into mid-septal group(n=16)and low-septal group(n=20).The clinical characteristics and cardiac electrical synchronization were compared between the two groups.Results:There were 21 male patients,mean age was(68±13)years old.There was no statistical difference in the type of brady-arrhythmia between the two groups(P=0.73).There were 61 implant attempts in these 36 patients,and there was no significant difference in the number of attempts,procedure time,and pacemaker parameters between the two groups,but the average procedure time tended to be shorter in the low-septal group([84±37]minutes vs.[105±35]minutes,P=0.09).In terms of electrical synchronization,there was no statistical difference in QRS duration between the low-septal group and the mid-septal group([162.0±21.1]ms vs.[174.0±14.8]ms,P=0.20).There were no vascular puncture complications,cardiac perforation,or pericardial tamponade during the procedure.There were no complications and readmissions related to the leadless pacemaker during follow-up period.Conclusions:Our results show that the implantation of a leadless pacemaker in the low ventricular septum is safe and effective,has a similar impact on cardiac electrical synchronization as mid-septal pacing.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.