ObjectiveTo investigate the effect of different exercise interventions on metabolism and liver parameters in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide evidence-based recommendations for clinical exercise rehabilitation. MethodsThis study was conducted according to the PRISMA guidelines， and the protocol was registered on the PROSPERO platform， with a registration number of CRD42025641717. PubMed， Web of Science， Scopus， Wiley Online Library， CNKI， Wanfang Data， and VIP were searched for related articles published up to September 2024. The Cochrane tool for assessing risk of bias was used to assess the quality of articles， and Stata MP 17.0 was used to perform the network meta-analysis. ResultsA total of 57 articles were included， involving 2 648 patients. The results showed that aerobic exercise combined with resistance exercise had the best effect in improving body mass index （mean difference ［WMD］=-0.97， 95% confidence interval ［CI］： -1.66 to -0.28］， P<0.05， surface under the cumulative ranking curve ［SUCRA］=85.4） and triglycerides （WMD=-29.6， 95%CI： -46.66 to 12.54， P<0.05， SUCRA=87.3）； resistance exercise was the optimal intervention method for improving total cholesterol （WMD=-15.99， 95%CI： -24.19 to -7.79， P<0.05， SUCRA=79.9） and glutamine transaminase （WMD=-8.08， 95%CI： -12.13 to -4.02， P<0.05， SUCRA=87.3）； low-intensity aerobic exercise had the best effect in improving aspartate aminotransferase （WMD=-4.3， 95%CI： -8.45 to -0.15， P<0.05， SUCRA=73.5）， gamma-glutamyl transpeptidase （GGT） （WMD=-3.26， 95%CI： -7.79 to 1.27， P>0.05， SUCRA=82.3）， and glycated hemoglobin （HbA1c） （WMD=-0.6， 95%CI： -2.02 to 0.82， P>0.05， SUCRA=78.8）； moderate-intensity aerobic exercise was the optimal intervention modality to improve Homeostasis Model Assessment of Insulin Resistance （WMD=-0.92， 95%CI： -1.51 to -0.33， P<0.05， SUCRA=69.4）. It should be noted that there were no significant differences in HbA1c and GGT across different exercise interventions （all P>0.05）， suggesting that there was currently no sufficient statistical evidence to support that exercise could improve these two indicators. ConclusionBased on the comprehensive league table and cumulative probability ranking， aerobic exercise combined with resistance exercise， resistance exercise， and low- and moderate-intensity aerobic exercise may be the best exercise modality for improving key indicators in MAFLD patients， and targeted exercise modalities should be selected for intervention against different indicators； however， due to limitations of the original studies， further studies are needed for validation and exploration.

Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

ObjectiveTo investigate the effects of Zuoguiwan on osteoclast activation induced by breast cancer and its mechanism. MethodsTo simulate breast cancer-induced osteoclastic bone metastasis， RAW264.7 cells were cultured in conditioned medium containing 50% supernatant of MDA-MB-231 breast cancer cells. The dosages of Zuoguiwan used in the experiment were sera containing 5% and 10% Zuoguiwan. Tartrate-resistant acid phosphatase （TRAP） staining was used to detect osteoclast activation. Enzyme-linked immunosorbent assay （ELISA） was used to measure Cathepsin K secretion from RAW264.7 cells. Real-time quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression levels of osteocalcin （OCN） and bone sialoprotein （BSP）. Immunoprecipitation was employed to detect the interaction between Runt-related transcription factor 2 （Runx2） and core binding factor β subunit （CBF-β）. Western blot was used to assess the protein expression of Runx2， phosphorylated Runx2 （p-Runx2）， extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， p38 mitogen-activated protein kinase （MAPK）， p-p38 MAPK， and CBF-β. ResultsCompared with the blank group， the MDA-MB-231 cell supernatant group showed a significant increase in TRAP-positive cell counts and Cathepsin K secretion. Meanwhile， the expression levels of p-Runx2， Runx2-CBF-β interaction， BSP and OCN mRNA， p-p38 MAPK， and p-ERK1/2 proteins were significantly decreased （P<0.01）. Compared with the MDA-MB-231 cell supernatant group， Zuoguiwan-containing sera significantly reduced TRAP-positive cell counts and Cathepsin K secretion （P<0.01）， significantly increased p-Runx2， BSP and OCN mRNA expression， as well as p-p38 MAPK and p-ERK1/2 protein levels， and promoted the interaction between Runx2 and CBF-β （P<0.01）. No significant change in Runx2 expression was observed. Compared to the blank group， the BVD-523 group showed significantly lower expression of p-p38 MAPK and p-ERK1/2 proteins （P<0.01）. Compared with the BVD-523 group， both low and high concentration Zuoguiwan-containing sera groups showed significantly higher p-p38 MAPK expression （P<0.01）， and the high concentration Zuoguiwan group also exhibited a significant increase in p-ERK1/2 expression （P<0.01）， while no statistical difference was found in the low-dose group. ConclusionZuoguiwan inhibits osteoclast activation by inducing phosphorylation of the key transcriptional regulator Runx2 in intra-osteoclast bone formation， and this process is closely associated with the activation of the p38 MAPK/ERK signaling pathway.

Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Objective:To investigate a case of antibodies against high-frequency erythrocyte antigens and elucidate the genetic mechanism underlying the blood group.Methods:A Lan-negative patient referred to the Zhejiang Blood Center by Quzhou Hospital of Traditional Chinese Medicine in August 2016 was selected as the study subject. A retrospective study was conducted to collect the proband′s clinical data. The proband′s erythrocyte antigens and unexpected serum antibodies were identified using tube saline and microcolumn agglutination anti-human globulin methods. Antibody specificity was determined by treating erythrocytes with 7 enzymes and 2 chemical reducing agents. Genomic DNA was extracted from the proband′s blood sample for whole genome sequencing (WGS) and erythrocyte blood group gene analysis, with validation by Sanger sequencing. Multiple bioinformatics tools were used to analyze the pathogenicity of the variant. The rare blood group and unexpected antibody specificity were comprehensively determined based on the results of serological and genetic testing. This study has been approved by the Zhejiang Provincial Blood Center Medical Ethics Committee(Ethics No.20190201).Results:The proband was a 91-year-old Han Chinese male with prostatitis, cystitis, and malnutrition in conjunct with emaciation. He had a history of multiple erythrocyte transfusions without observable adverse reactions. Prior to the most recent transfusion, major crossmatch agglutination was observed, which prompted antibody identification. Antibodies against high-frequency antigens were detected in the proband′s serum, with enzyme and reducing agent treatments ruling out antibody specificities associated with 17 blood group systems, e. g., MNS, LU, KEL. WGS analysis identified 4 525 SNPs and 1 046 INDEL variants among erythrocyte blood group genes. Further screening revealed that the proband had a rare blood group due to a homozygous rs755723161 variant. This variant in the ABCB6 gene (c.459delC) has led to a frameshifting mutation (p.Trp154GlyfsTer96), resulting in the Lan-negative rare blood group with a high-frequency antigen deficiency and the production of IgG anti-Lan antibodies in the serum. Conclusion:This study has identified anti-Lan alloantibodies in a Lan-negative patient and, for the first time, elucidated the ABCB6 gene variant underlying the Lan-negative rare blood group in the Chinese population.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.