AIM:The aim of this study was to explore the effects of Yiqi-Yangyin-Quyu prescription(YP)on skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome(SS),and to clarify the role of hy-droxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta(Hadhb)in mediating the effect of YP on skeletal muscle in SS.METHODS:The SS mice underwent YP treatment for 8 weeks.The morphological changes of the submandibular gland and muscle tissue were examined using hematoxylin-eosin staining.The mitochondrial status in mus-cle tissue was assessed through transmission electron microscopy.Additionally,combined transcriptome and proteome se-quencing was conducted on skeletal muscle samples.The omics sequencing results were validated by RT-qPCR.Immuno-fluorescence was used to confirm the levels of key proteins involved in the P53/peroxisome proliferator-activated receptor gamma(PPARG)signaling pathway.Immunohistochemistry and Western blot were employed to determine the levels of Hadhb key targets.RESULTS:Combined transcriptome and proteome analysis identified 1 523 differentially expressed genes(DEGs)and 182 differentially expressed proteins(DEPs)between the muscle tissue of SS mice(model group)and that of control animals(ICR group),12 of which showed co-differential expression at both transcriptomic and proteomic levels.Compared with model group,1 232 genes and 432 proteins were found to be differentially expressed in the muscle tissue of the mice in YP group.Among these,23 exhibited co-differential expression at both mRNA and protein levels.Gene Ontology(GO)analysis showed that the DEGs and DEPs between ICR and model groups were mainly involved in ener-gy metabolism and fatty acid oxidation,while the DEGs and DEPs between YP and model groups were primarily associated with sarcomere tissue and actin structure.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indi-cated that the DEGs and DEPs between ICR and model groups and between model and YP groups were enriched in the com-plement and coagulation cascade and lipid and pyruvate metabolism.The RT-qPCR validation results were consistent with those of the transcriptome analysis.Furthermore,the protein expression of the tumor suppressor P53 was significantly de-creased in YP group compared with model group,whereas that of PPARG was significantly increased.Western blot analy-sis showed that compared with ICR group,Hadhb protein expression was significantly decreased in model group,whereas the opposite trend was detected in YP group.CONCLUSION:The SS-related skeletal muscle damage is closely related to amino acid metabolism disorder and fatty acid degradation.Treatment with YP modulates innate immune defenses,lipid metabolism and energy metabolism in SS,and Hadhb is the key target of YP in SS-related skeletal muscle.

Objective:To compare pregnancy outcomes between patients undergoing combined hysteroscopy and hysterosalpingo-contrast sonography (HyCoSy) versus hysteroscopy alone prior to intrauterine insemination, and to evaluate the safety and clinical value of the combined procedure in the diagnosis and treatment of infertility.Methods:A retrospective analysis was conducted on clinical data from 385 patients who underwent hysteroscopy at Peking University Third Hospital between October 1, 2020 and September 30, 2022, and subsequently received their first cycle of artificial insemination with donor sperm (AID) within six months. Pregnancy outcomes were compared between the group receiving combined hysteroscopy with four-dimensional HyCoSy (hysteroscopy+4D-HyCoSy group) and the group receiving hysteroscopy alone (hysteroscopy group). Multivariate logistic regression was used to analyze factors influencing pregnancy outcomes after AID.Results:Among the 385 patients included, 79 achieved clinical pregnancy. The clinical pregnancy rate (24.9%, 53/213) and live birth rate (21.1%, 45/213) in the hysteroscopy+4D-HyCoSy group were significantly higher than those in the hysteroscopy group [15.1% (26/172) and 12.8% (22/172), respectively; all P<0.05]. There was no significant difference in tubal patency between the two groups ( P>0.05); however, the time interval from tubal patency assessment to intrauterine insemination was significantly longer in the hysteroscopy group compared to the hysteroscopy+4D-HyCoSy group (median: 4.0 vs 2.0 months; P<0.001). Multivariate analysis showed that double insemination significantly increased clinical pregnancy rate compared to single insemination ( OR=2.42, 95% CI: 1.02-5.72; P=0.044). An interval exceeding 6 months between tubal patency assessment and intrauterine insemination was identified as a risk factor for reduced clinical pregnancy ( OR=0.35, 95% CI: 0.14-0.92; P=0.047). Additionally, neither the time interval from hysteroscopy to intrauterine insemination nor hysteroscopic findings and pathological diagnoses had significant effects on clinical pregnancy rates (all P>0.05). Conclusions:The combination of hysteroscopy and HyCoSy provides a safe and efficient approach for fertility assessment in infertile patients and improves clinical pregnancy rate and live birth rate in intrauterine insemination cycles. Hysteroscopy is recommended for patients with suspected endometrial or intrauterine abnormalities. If no previous tubal patency assessment has been performed or the last assessment was more than six months prior, combined hysteroscopy and HyCoSy may be considered to enhance the likelihood of clinical pregnancy.

Objective:To compare pregnancy outcomes between patients undergoing combined hysteroscopy and hysterosalpingo-contrast sonography (HyCoSy) versus hysteroscopy alone prior to intrauterine insemination, and to evaluate the safety and clinical value of the combined procedure in the diagnosis and treatment of infertility.Methods:A retrospective analysis was conducted on clinical data from 385 patients who underwent hysteroscopy at Peking University Third Hospital between October 1, 2020 and September 30, 2022, and subsequently received their first cycle of artificial insemination with donor sperm (AID) within six months. Pregnancy outcomes were compared between the group receiving combined hysteroscopy with four-dimensional HyCoSy (hysteroscopy+4D-HyCoSy group) and the group receiving hysteroscopy alone (hysteroscopy group). Multivariate logistic regression was used to analyze factors influencing pregnancy outcomes after AID.Results:Among the 385 patients included, 79 achieved clinical pregnancy. The clinical pregnancy rate (24.9%, 53/213) and live birth rate (21.1%, 45/213) in the hysteroscopy+4D-HyCoSy group were significantly higher than those in the hysteroscopy group [15.1% (26/172) and 12.8% (22/172), respectively; all P<0.05]. There was no significant difference in tubal patency between the two groups ( P>0.05); however, the time interval from tubal patency assessment to intrauterine insemination was significantly longer in the hysteroscopy group compared to the hysteroscopy+4D-HyCoSy group (median: 4.0 vs 2.0 months; P<0.001). Multivariate analysis showed that double insemination significantly increased clinical pregnancy rate compared to single insemination ( OR=2.42, 95% CI: 1.02-5.72; P=0.044). An interval exceeding 6 months between tubal patency assessment and intrauterine insemination was identified as a risk factor for reduced clinical pregnancy ( OR=0.35, 95% CI: 0.14-0.92; P=0.047). Additionally, neither the time interval from hysteroscopy to intrauterine insemination nor hysteroscopic findings and pathological diagnoses had significant effects on clinical pregnancy rates (all P>0.05). Conclusions:The combination of hysteroscopy and HyCoSy provides a safe and efficient approach for fertility assessment in infertile patients and improves clinical pregnancy rate and live birth rate in intrauterine insemination cycles. Hysteroscopy is recommended for patients with suspected endometrial or intrauterine abnormalities. If no previous tubal patency assessment has been performed or the last assessment was more than six months prior, combined hysteroscopy and HyCoSy may be considered to enhance the likelihood of clinical pregnancy.

Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

AIM:The aim of this study was to explore the effects of Yiqi-Yangyin-Quyu prescription(YP)on skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome(SS),and to clarify the role of hy-droxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta(Hadhb)in mediating the effect of YP on skeletal muscle in SS.METHODS:The SS mice underwent YP treatment for 8 weeks.The morphological changes of the submandibular gland and muscle tissue were examined using hematoxylin-eosin staining.The mitochondrial status in mus-cle tissue was assessed through transmission electron microscopy.Additionally,combined transcriptome and proteome se-quencing was conducted on skeletal muscle samples.The omics sequencing results were validated by RT-qPCR.Immuno-fluorescence was used to confirm the levels of key proteins involved in the P53/peroxisome proliferator-activated receptor gamma(PPARG)signaling pathway.Immunohistochemistry and Western blot were employed to determine the levels of Hadhb key targets.RESULTS:Combined transcriptome and proteome analysis identified 1 523 differentially expressed genes(DEGs)and 182 differentially expressed proteins(DEPs)between the muscle tissue of SS mice(model group)and that of control animals(ICR group),12 of which showed co-differential expression at both transcriptomic and proteomic levels.Compared with model group,1 232 genes and 432 proteins were found to be differentially expressed in the muscle tissue of the mice in YP group.Among these,23 exhibited co-differential expression at both mRNA and protein levels.Gene Ontology(GO)analysis showed that the DEGs and DEPs between ICR and model groups were mainly involved in ener-gy metabolism and fatty acid oxidation,while the DEGs and DEPs between YP and model groups were primarily associated with sarcomere tissue and actin structure.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indi-cated that the DEGs and DEPs between ICR and model groups and between model and YP groups were enriched in the com-plement and coagulation cascade and lipid and pyruvate metabolism.The RT-qPCR validation results were consistent with those of the transcriptome analysis.Furthermore,the protein expression of the tumor suppressor P53 was significantly de-creased in YP group compared with model group,whereas that of PPARG was significantly increased.Western blot analy-sis showed that compared with ICR group,Hadhb protein expression was significantly decreased in model group,whereas the opposite trend was detected in YP group.CONCLUSION:The SS-related skeletal muscle damage is closely related to amino acid metabolism disorder and fatty acid degradation.Treatment with YP modulates innate immune defenses,lipid metabolism and energy metabolism in SS,and Hadhb is the key target of YP in SS-related skeletal muscle.

Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure （CNKI），Wanfang Data Knowledge Service Platform （WF），VIP，SinoMed，Embase，PubMed，Web of Science （WOS），and the Cochrane Library were searched for randomized controlled trials （RCT） of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15，2023. The literature was screened and extracted，and the risk of bias tool 2.0 （RoB2） was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment，Development and Evaluation （GRADE） was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance，Work-related Injury Insurance and Maternity Insurance （2022） and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment，and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate，Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets，Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets，Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan，Wenyading capsules combined with enalapril，and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure （SBP），diastolic blood pressure （DBP），cholesterol （TC），triglyceride （TG），low density lipoprotein cholesterol （LDL-C），and high density lipoprotein cholesterol （HDL-C）. There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B，that of DBP as C，and that of total TC，TG，LDL-C，and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance，and were recommended for 7，6 and 3 times in the guidelines and consensus，respectively. ConclusionCompared with simple medicine treatment，Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid，and shows higher safety. Among them，Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However，the quality of evidence in related clinical studies was low. In terms of trial design，large-sample，multi-center，blinded randomized controlled trials based on the consolidated standards of reporting trials （CONSORT） statement are still needed for comprehensive trial designs and reporting，to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine，so as to provide higher quality evidence-based research evidence for clinical decision-making.

ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension， synthesize and update the evidence， form expert consensus， and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure （CNKI）， WanFang Data Knowledge Service Platform （WanFang）， Vip Chinese Science and Technology Journal Database （VIP）， Chinese Biomedical Literature Service System （Sinomed）， National Library of Medicine （PubMed）， Cochrane Library， Web of Science， and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31， 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment， Development， and Evaluation profiler （GRADEprofiler） 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included， and the results of literature quality evaluation and risk of bias showed that 70.31% （45/64） of the studies indicated some risks， and 29.69% （19/64） indicated high risks. Compared with conventional western medicines， the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure （SBP） and diastolic pressure （DBP）， increase the effective rate of antihypertensive， reduce the incidence of adverse reactions， endothelin-1， and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive， and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive， without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive， and Xinmaitong capsules decreased DBP， with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally， four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension， antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety， but they are mostly weak recommendations in terms of efficacy， and more high-quality evidence is needed.

ObjectiveTo systematically collect， analyze， and evaluate the randomized controlled trials （RCT） of Chinese patent medicine combined with western medicine in the treatment of hypertension， map the evidence， and provide reference for the future clinical research and formulation of guidelines and policies. MethodThe relevant articles were retrieved from China Biology Medicine disc， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， PubMed， Embase， and Cochrane Library with the time interval from inception to December 31， 2022. The RCT of Chinese patent medicines combined with western medicine in the treatment of hypertension were included. The research characteristics and methodological quality were analyzed and evaluated. ResultA total of 330 RCTs of treating hypertension with Chinese patent medicines combined with Western medicine were included in this study， all of which were published in Chinese. These RCTs involved 88 Chinese patent medicines and 37 788 patients， and 46% of RCT had the sample size ≥100 patients. Eighty-seven percent of RCT showed the study period within 3 months. All the interventions in the RCTs were Chinese patent medicine + western medicine vs western medicine. Among the evaluation indicators， blood pressure， response rate， TCM syndrome score， endothelial cell function， and safety were mainly concerned. In terms of methodological quality， most articles did not mention the generation of random sequences， allocation concealment， or blinding method. The blinding evaluation of outcomes showed low risks of bias， and there was insufficient information to judge whether there was selective bias or other bias. ConclusionThere were many Chinese patent medicines used in combination with western medicine in the treatment of hypertension， and they were mainly taken orally. The existing RCT had problems such as small sample size， unclear clinical value positioning， imperfect design failing to reflect the value of Chinese patent medicines， unreasonable measurement indicators， and non-standard measurement methods. Future research should solve the above problems， improve the research quality， value， and authenticity， and enhance the reliability and extension of evidence.

BACKGROUND:Knee osteoarthritis is a common clinical degenerative joint disease characterized by chronic inflammation and oxidative stress.Resveratrol has anti-inflammatory and anti-oxidative stress biological effects,and therefore it can be used symptomatically and expected to provide a new strategy for the treatment of knee osteoarthritis. OBJECTIVE:To investigate the therapeutic effect and mechanism of resveratrol on knee osteoarthritis in rats through the silence information regulator 1(SIRT1)/forkhead transcription factor O1(FOXO1)pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into control group,model group,low-dose resveratrol group,and high-dose resveratrol group,with 10 rats in each group.Knee osteoarthritis models were established in the model group,low-dose resveratrol group,and high-dose resveratrol group.A mixture of 4%papain solution and 0.3 mol/L cysteine solution(1:1 for 0.5 hours;20 μL)was injected at 1,4,and 7 days after modeling.Rats in the low-dose and high-dose resveratrol groups were injected with 25 and 100 mg/kg resveratrol through the articular cavity at 1 day after successful modeling,while those in the control and model groups were injected with equivalent volume of physiological saline through the articular cavity.After 28 days of treatment,the maximum knee joint activity was measured;the levels of oxidative stress indicators and inflammatory factors in the synovial fluid of the knee joint were analyzed by radioimmunoassay and ELISA;the content of collagen fibers in the knee joint was analyzed by safranin O-fast green staining;the degree of arthritic lesions was analyzed using the Mankin histological score;and the levels of SIRT1 and FOXO1 in the knee joint were detected by western blot assay. RESULTS AND CONCLUSION:Compared with the model group,the maximum knee flexion and extension angles of rats significantly increased in the low-dose and high-dose resveratrol groups,and were significantly higher in the high-dose group than the low-dose group(P<0.05).Compared with the model group,the levels of superoxide dismutase and glutathione peroxidase in the knee joint fluid of rats significantly increased in the low-dose and high-dose resveratrol groups.The level of malondialdehyde significantly decreased in both resveratrol groups,and the level in the high-dose resveratrol group was significantly better than that in the low-dose resveratrol group(P<0.05).Compared with the model group,the low-dose and high-dose resveratrol groups showed a significant decrease in the levels of interleukin 1β,interleukin 6 and tumor necrosis factor α in the knee joint fluid of rats,and the levels of these inflammatory factors were significantly lower in the high-dose resveratrol group than the low-dose resveratrol group(P<0.05).Compared with the model group,the content of collagen fibers in the knee joint was significantly increased in both resveratrol groups,and the high-dose resveratrol group showed a higher content of collagen fibers than the low-dose resveratrol group(P<0.05).Compared with the model group,the expression level of SIRT1 in the knee joints of rats significantly increased in both resveratrol groups,while the level of acetylated FOXO1 significantly decreased(P<0.05).The magnitude of changes was significantly better in the high-dose group than the low-dose group.To conclude,resveratrol significantly improves the levels of oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis and alleviates arthritic symptoms in a dose-dependent manner,possibly through the SIRT1/FOXO1 pathway.