The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

[Objective] To analyse the distribution of antigen phenotypes in the Rh, MNS and Kidd blood group systems of Han and Tujia blood donors in Chongqing, and to provide data support for the establishment of an expanded blood group antigen phenotype database and the development of expanded blood group coordinated transfusion in blood donors. [Methods] The antigens of Rh, MNS and Kidd blood group systems in Han and Tujia blood donors in Chongqing were detected by test-tube method, and the Hardy-Weinborg anastomosis of the three blood group systems was calculated. Pearson's chi-square test and Fisher's exact probability method were used to compare the differences in phenotypic distribution frequencies among different regions and ethnic groups. [Results] Han and Tujia blood donors accounted for the highest proportion of CCee in the antigenic phenotype of the Rh blood group system, followed by CcEe, and then Ccee and ccEE. Tujia blood donors accounted for 52.02% of CCee, which was higher than that of Han blood donors (47.24%), while Han blood donors accounted for 32.20% of CcEe, which was higher than that of Tujia blood donors (28.94%). In the antigenic phenotype of the MNS blood group system, the blood donors of Han nationality and Tujia were MN>MM>NN,. The antigen phenotype distribution frequency of the Kidd blood group system was highest for Jk(a+b+) among both Han and Tujia blood donors, and the blood donors of Han nationality were Jk(a+b+)>Jk(a+b+), while those of Tujia were Jk(a-b+)>Jk(a+b-). The antigens of the three blood groups of Han and Tujia blood donors were consistent with the Hardy-Weinberg balance(P>0.05). There was no statistically significant difference in the frequency of antigen phenotypes of the three blood group systems between Han and Tujia blood donors(P>0.05). There were statistically significant differences in the phenotypic distribution frequency of Rh antigens between Chongqing and Xi'an, Zhejiang, Shantou, Foshan, Nanning and Yangzhou(P<0.05), but not with Guang'an and Shenzhen(P>0.05). There were statistically significant differences in the phenotypic distribution frequency of Rh antigens between Han, Tujia, Zang, Mongolian, Korean and Hani ethnic groups in Chongqing(P<0.05). There were statistically significant differences in the phenotypic distribution frequency of MNS antigens between Han blood donors in Chongqing and Urumqi, Hainan and Yuncheng, but not with Xi'an and Wenzhou. There was a statistically significant difference in the phenotypic distribution frequency of MNS antigen between Tujia blood donors in Chongqing and Urumqi and Hainan(P<0.05), but there was no significant difference in the phenotypic distribution frequency of MNS antigen between Tujia blood donors in Chongqing, Urumqi and Hainan(P>0.05). There was a statistically significant difference in the phenotypic distribution frequency of Kidd antigens between blood donors in Chongqing and Harbin(P<0.05), but not in Huizhou, Wenzhou and Yichang(P>0.05). [Conclusion] The population in Chongqing has multi-ethnic characteristics, and the antigenic phenotypes of Rh, MNS and Kidd blood group systems exhibit diversity and regional differences. Establishing an expanded blood bank can provide more options for precision blood transfusion.

[Objective] To assess the data characteristics of quality monitoring indicators for red blood cell (RBC) preparations, so as to provide reference for continuous improvement of blood quality. [Methods] The quality inspection data of 6 types of RBC preparations from Chongqing blood center from 2019 to 2023 were summarized. For the same indicators, the numerical range of quality indicators was monitored by comparing different types of preparations with the national standard GB18469. The loss and/or damage to RBCs caused by different preparation process were compared, and the impact of different preparation processes on the quality of RBCs was discussed. [Results] The appearance and sterility test compliance rates of the six types of RBC preparations were both 100%, while the compliance rates of other items were all ≥75%. The compliance rate of hematocrit for suspended RBCs was the lowest at 75%, with a median of 0.52, which was close to the lower limit of GB18469, while the medians of hematocrit for the other types were all at the midline level of GB18469. The Hb content for different types of RBCs was significantly higher than the corresponding requirements of GB18469 (P<0.05). The hemolysis rate at the end of storage for different types of RBCs was significantly lower than the requirements of GB18469 (P<0.05). The 1 U leukoreduction process resulted in a hemoglobin content loss of about 5% and had a significant impact on the hemolysis rate at the end of storage (P<0.05). The washing process resulted in a hemoglobin content loss of <3% and had no significant impact on the hemolysis rate at the end of storage (P>0.05). The concentration process resulted in a hemoglobin content loss of <3% and had a significant impact on the hemolysis rate at the end of storage (P<0.05). [Conclusion] The impact of different processes on RBC preparations is within a controllable range and meets the requirements of GB18469. The quality monitoring data can provide a reference for clinical blood selection, effectiveness evaluation and revision of related standards.

BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

Objective To systematically evaluate and integrate qualitative studies on perception of exercise behaviors in community-dwelling older adults with frailty,and to provide references for clinical development of targeted exercise intervention strategies.Methods A systematic search of PubMed,Medline,Embase,PsycINFO,the Cochrane Library,SinoMed,Wanfang Database,CNKI,and VIP Database for qualitative studies on perception of exercise behaviors in older adults with frailty in the community was conducted from the inception of the databases to June 2024.Literature quality was evaluated using the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016 edition),and Meta-synthesis was performed using the theme synthesis method.Results A total of 10 papers were included,grouped into 10 categories and integrated into the 3 domains of the capability,opportunity,and motivation-behavior model(COM-B model),i.e.Preparation for exercise behavior is influenced by capability factors(physical reserve,knowledge reserve,psychological preparation);stage-specific motivational evolution promotes the internalization of exercise behavior(guiding,focusing,stimulating,and maintaining);external conditions provide opportunities for exercise behavior(individual interaction,community environment,and social support).Conclusion Perceptions of exercise behavior among community-dwelling older adults with frailty or are complex and influenced by a variety of factors.Future exercise intervention strategies should consider modifiable factors,enhance knowledge education,stimulate intrinsic motivation,and solidify external conditions,while also accommodating individual differences and preferences,so as to promote exercise participation and health enhancement in this group.

OBJECTIIVE:The positive role of exercise intervention in the prevention and treatment of sarcopenia has received widespread attention,but the optimal exercise dose for elderly sarcopenic patients still needs to be further determined.The article explored the dose-effect relationship between various elements of exercise prescription and the improvement of muscle mass,muscle strength and physical function in community-dwelling elderly patients with sarcopenia,aiming to provide scientific support for the development of exercise prescription for community-dwelling elderly patients with sarcopenia.METHODS:Literature published from the inception to October 9,2024 in PubMed,EMBASE,Scopus,Web of Science,CNKI,WanFang,VIP,and CBMdisc databases was systematically searched.Meta-analysis was performed using RevMan 5.3 software.Standardized mean difference(SMD)and its 95％CI were used as effect statistics.RESULTS:(1)A total of 11 randomized controlled trials were included,with 348 in the trial group and 304 in the control group.(2)Meta-analysis results showed that exercise improved appendicular skeletal muscle mass index,grip strength,and walking speed in elderly patients with sarcopenia(SMDs 0.46,0.63,0.67,P＜0.05).(3)When the frequency of exercise was 2-3 days/week,appendicular skeletal muscle mass index(SMD=0.57,95％CI:0.28-0.86,P＜0.001),grip strength(SMD=0.70,95％CI:0.37-1.02,P＜0.001),and walking speed(SMD=0.69,95％CI:0.20-1.18,P=0.006)were effectively improved in elderly patients with sarcopenia.(4)When the duration of exercise was 25-60 minutes per session,appendicular skeletal muscle mass index(SMD=0.28,95％CI:0.07-0.50,P=0.01),grip strength(SMD=0.37,95％CI:0.16-0.59,P＜0.001),and walking speed(SMD=0.39,95％CI:0.06-0.73,P=0.02)were effectively improved in elderly patients with sarcopenia.(5)When the exercise intensity was moderate,appendicular skeletal muscle mass index(SMD=0.69,95％CI:0.35-1.03,P＜0.001),and grip strength(SMD=0.36,95％CI:0.09-0.64,P=0.009),and walking speed(SMD=0.91,95％CI:0.34-1.47,P=0.002)were effectively improved in elderly patients with sarcopenia.(6)When the dose of exercise cycle was 8-12 weeks,appendicular skeletal muscle mass index(SMD=0.42,95％CI:0.20-0.64,P＜0.001),grip strength(SMD=0.45,95％CI:0.26-0.64,P＜0.001),and walking speed(SMD=0.76,95％CI:0.27-1.25,P=0.002)were effectively improved in elderly patients with sarcopenia.CONCLUSION:Active,regular exercise can improve muscle health in older adults with sarcopenia.It is recommended that older patients with sarcopenia exercise at least 2 to 3 days per week,25 to 60 minutes each time,lasting for 8 to 12 weeks of moderate intensity exercise to improve muscle health.

[Objective]To analyze the clinical characteristics,efficacy of growth hormone(GH)therapy,and follow-up of a child with Rauch-Steindl syndrome(RAUST)caused by NSD2 gene mutation,aiming to enhance pediatricians'understanding of this disorder.[Methods]We summarized the clinical features,gene test results,outcomes of GH therapy,and follow-up data of a child with RAUST syndrome caused by NSD2 mutation admitted to the Pediatric Endocrinology Department of Sun Yat-sen Memorial Hospital in April 2017,and then conducted a comparative analysis with relevant literature.[Results]The 2.9-year-old boy at initial visit was born prematurely at 36 weeks of gestation,with a birth weight of 1.7 kg and a body length of 42.0 cm.Clinical manifestations included intrauterine growth retardation,delayed language and motor development,extreme short stature(82.0 cm,-3.7 SD),emaciation,and distinctive facial features(triangular face,narrow jaw,prominent forehead,arched eyebrows,sparse eyebrows,high anterior hairline,crowded dentition),accompanied by bilateral cryptorchidism.Bone age was delayed by 1.4 years.Karyotyping and chromosomal microarray analysis were normal.GH therapy initiated at 3.8 years old yielded annual growth rates of 4.9-6.6 cm/year.When the treatment was discontinued at the age of 8.0,the boy's height was 113.7 cm(-3.0 SD),with subsequent decline in growth velocity.Whole exome sequencing in July 2024 identified a frameshift variant c.4028del(p.Pro1343Glnfs*49)in NSD2,which was confirmed as de novo pathogenic variation by parental Sanger sequencing.[Conclusions]This study reports the clinical features of RAUST syndrome caused by NSD2 mutation and explores the long-term efficacy of GH therapy.The findings contribute to a better understanding of this rare syndrome and further optimize its diagnosis and management.

Objective:To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. Methods:A child diagnosed with CDCBM4 and epilepsy at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097).Results:The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c. 776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+ PS3+ PM2_Supporting+ PP3). Combining the child′s clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. Conclusion:Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c. 776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. METHODS: A child diagnosed with CDCBM4 and epilepsy at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097). RESULTS: The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c.776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+PS3+PM2_Supporting+PP3). Combining the child's clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. CONCLUSION Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c.776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.
Humans ; Female ; Epilepsy/genetics* ; Malformations of Cortical Development/genetics* ; Infant ; Phenotype ; Exome Sequencing ; Microtubule-Associated Proteins/genetics*