OBJECTIVES: To summarize the clinical and genetic characteristics of end-stage renal disease caused by PLCE1 gene mutations. METHODS: A retrospective analysis of the clinical and genetic features of three children from a family with PLCE1 gene mutations was conducted, along with a literature review of hereditary kidney disease cases caused by PLCE1 gene mutations. RESULTS: The proband was an 8-year-old male presenting with nephrotic syndrome stage 4 chronic kidney disease. Renal biopsy showed focal segmental glomerulosclerosis. Two years and five months after kidney transplantation, the patient had persistent negative proteinuria and normal renal function. Whole-exome sequencing identified two pathogenic heterozygous variants: c.961C>T and c.3255_3256delinsT, with c.3255_3256delinsT being a novel mutation. Family screening revealed no renal involvement in the parents, but among five siblings, one brother died at age of 4 years from end-stage renal disease. A 7-year-old sister presented with proteinuria and bilateral medullary sponge kidney, with proteinuria resolving after one year of follow-up. A 3-year-old brother died after kidney transplantation due to severe pneumonia. The literature review included 45 patients with hereditary kidney disease caused by PLCE1 gene mutations. The main clinical phenotype was nephrotic syndrome (87%, 39/45), and renal pathology predominantly showed focal segmental glomerulosclerosis (57%, 16/28). No mutation hotspots were identified. CONCLUSIONS Compound heterozygous mutations in the PLCE1 gene can lead to rapid progression of the disease to end-stage renal disease, with favorable outcomes following kidney transplantation. Family screening is crucial for early diagnosis, and medullary sponge kidney may be a novel phenotype associated with these gene mutations.
Humans ; Male ; Proteinuria/genetics* ; Kidney Failure, Chronic/etiology* ; Child ; Mutation ; Female ; Child, Preschool ; Retrospective Studies ; Phosphoinositide Phospholipase C

OBJECTIVE: To explore the role of nuclear receptor-binding SET-domain protein 1 (NSD1) in the pathogenesis of nonobstructive azoospermia (NOA) by regulating the expressions of relevant genes. METHODS: We detected the expression of NSD1 in the testis tissue of 7 male patients with obstructive azoospermia (OA) and 18 with NOA by qPCR and immunofluorescence assay, and determined the modification level of H3K36me2 in the testes of two groups of patients by immunofluorescence staining, Western blot and immunoprecipitation (IP). We examined the difference in the enrichment of H3K36me2 in the testis tissue by chromatin IP-based sequencing (ChIP-Seq), analyzed the genomic distribution and target genes using bioinformatics, and verified the expression levels of the target genes in the testes of the two groups of patients by qPCR. RESULTS: Compared with the patients with OA, those with NOA showed dramatically decreased mRNA and protein expressions of NSD1 (P=0.000 8). The binding of NSD1 to H3K36me2 was observed in the testis tissue of both the two groups of patients, while the modification level of H3K36me2 was evidently reduced in the NOA males. H3K36me2 was distributed mainly in the intergenic region in the testes of the two groups of patients, but the enrichment of H3K36me2 was obviously decreased in the NOA group. The differentially H3K36me2-enriched genes were involved in various biological processes, including tissue development, and cell morphogenesis. Results of ChIP-Seq and qPCR showed significantly down-regulated expressions of the target genes KIT, SPO11 and ACRV1 in the testis tissue of the NOA males compared with those in the OA patients (P<0.01). CONCLUSION The levels of NSD1 and H3K36me2 are decreased in testis tissue of the NOA patient, H3K36me2 is highly enriched in the spermatogenesis-related key genes KIT, SPO11 and ACRV1, and the down-regulated expression of NSD1 impairs spermatogenesis.
Humans ; Male ; Azoospermia/genetics* ; Testis/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Histones/metabolism*

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

BACKGROUND: Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias. OBJECTIVE: Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP). SEARCH STRATEGY: We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics. INCLUSION CRITERIA: Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review. DATA EXTRACTION AND ANALYSIS: Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment. RESULTS: A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41). CONCLUSION The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans ; Acupuncture Analgesia ; Acupuncture Therapy ; Anesthesia ; Clinical Trials as Topic ; Registries

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Background and purpose:Deep learning methods can be used for automatic segmentation and detection of lymphocytes on pathological images.This study aimed to assess the performance of using variational autoencoding pre-training method for lymphocyte infiltration detection on pathological images,as well as the impact of removing tumor necrosis regions on model performance.Methods:Using variational autoencoding(VAE)pre-training method,pre-training was performed on a large number of unlabeled pathological images from the Cancer Genome Atlas(TCGA)database(TCGA-COAD and TCGA-READ)to obtain an auto-encoding pre-training model,and then a classifier model of lymphocyte infiltration was trained on the public data samples.To avoid confusion with necrotic regions,a Unet segmentation model for tumor necrotic regions was trained to remove the influence of tumor necrotic regions on lymphocyte identification.Results:The lymphocyte infiltration detection model pre-trained with the VAE model had an area under curve(AUC)of 0.979(95%CI:0.978-0.980),an accuracy of 92.5%(95%CI:92.3%-92.6%),a kappa value of 0.849,sensitivity of 0.908,specificity of 0.941,precision of 0.939,recall of 0.908,and F1 of 0.923 under the receiver operating characteristic(ROC)curve on the training set.The AUC for the validation set was 0.968(95%CI:0.964-0.972),the accuracy was 91.3%(95%CI:90.6%-92.0%),kappa value was 0.826,sensitivity was 0.898,specificity was 0.928,precision was 0.925,recall was 0.898,and F1 was 0.912.The results of Resnet18 model on the labeled dataset were as follows:accuracy of the validation set was 83.2%(95%CI:82.2%-84.1%),kappa value was 0.664,sensitivity was 0.823,specificity was 0.840,precision was 0.838,recall was 0.823 and F1 was 0.830.The Unet model that segmented the necrotic regions of the tumors had a final DICE of 0.78 for the training set,and 0.76 for the validation.After removing the necrotic region,the predictive performance of the pre-trained lymphocyte infiltration detection model using the VAE proposed in this article was improved to some extent,with the AUC on the validation set increasing from 0.968(95%CI:0.964-0.972)to 0.971(95%CI:0.968-0.975).The accuracy was 92.4%(95%CI:91.7%-93.0%),kappa value was 0.849,sensitivity was 0.928,specificity was 0.921,precision was 0.921,recall was 0.928,and F1 was 0.925.Conclusion:Using the variational autoencoding model pre-training method to classify the pathological pictures of lymphocyte infiltration can obtain better model performance compared with direct training,and removing the influence of tumor necrosis areas through Unet can further improve the performance of the model.

Aim To investigate the relationship between systemic inflammatory immune index(SII)and systemic inflammatory response index(SIRI)and the risk of in-hospital major adverse cardiovascular events(MACE)in patients with acute myocardial infarction(AMI).Methods Retrospective analysis was conducted on AMI patients ad-mitted to the Second Cardiovascular Disease Area of Suining Central Hospital from February 2021 to May 2022.Based on inclusion and exclusion criteria,246 patients were finally enrolled.According to whether MACE occurred during hospital-ization,they were divided into event group and non-event group,and baseline data of the two groups were compared.All variables except SII and SIRI were included in a univariate-multivariate Logistic regression analysis to screen factors af-fecting the risk of MACE,and were used as significant covariates for adjustment to evaluate the relationship between SII and SIRI and the risk of MACE respectively.Results The results of multivariate Logistic regression analysis showed that emergency PCI,left ventricular ejection fraction,albumin level and age were significant factors affecting the risk of in-hos-pital MACE in AMI patients(OR=0.432,95％CI:0.194～0.960,P=0.038;OR=0.930,95％CI:0.890～0.969,P=0.001;OR=0.730,95％CI:0.621～0.845,P＜0.001;OR=1.143,95％CI:1.070～1.228,P＜0.001),and a basic model was established based on this.After adjusting for the significant covariates,SII and SIRI were both independ-ent risk factors for in-hospital MACE(OR=1.004,95％CI:1.001～1.008,P=0.002;OR=4.467,95％CI:2.597～8.142,P＜0.001).The areas under the curves of SII and SIRI were 0.658 and 0.785,respectively,and the optimal cutoff values were 434.83 and 1.03.Restricted cubic spline analysis showed that SII(Nonlinear P=0.639)and SIRI(Nonlinear P=0.683)were linearly related to the risk of MACE after adjusting significant covariates.Threshold effect a-nalysis showed that when SIRI＞0.93,the risk of MACE began to increase.Conclusion Elevated levels of SII and SI-RI are independent risk predictors for the occurrence of in-hospital MACE in AMI patients.

Objective:To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods:The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results:In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions:Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.

Objective:To analyze the application value of MCV,MCH and HbA2 in screening for thalassemia in the population of childbearing age in Quanzhou area,and to determine the optimal screening cut-off value of relevant indicators in this area. Methods:2725 couples of childbearing age were included in the study and underwent routine blood test,capillary hemoglobin electrophoresis,and α and β thalassemia gene test. Statistical methods were used to analyze the distribution of thalassemia genotypes,and compare the performance of MCV,MCH,and HbA2 in screening various types of thalassemia. According to the ROC curve,the best cut-off values of MCV,MCH and HbA2 in screening for thalassemia in this area were determined. Results:In this study,a total of 1801 thalassemia carriers were detected,including 1341 cases of α-thalassemia,420 cases of β-thalassemia,and 40 cases of αβ compound thalassemia. The most common genotypes of α-thalassemia and β-thalassemia were--SEA/αα and β654/βN,respectively. ROC curves were drawn to evaluate the performance of MCV,MCH and HbA2 in screening for α-thalassemia,mild β-thalassemia,αβ compound thalassemia,silent α-thalassemia,mild α-thalassemia,and intermediate α-thalassemia. The maximum areas under the curves (AUC) were 0.747,0.865,0.724,0.486,0.812,0.841;0.747,0.846,0.703,0.479,0.796,0.903;0.613,0.980,0.909,0.465,0.674,0.996,respectively;and the best cut-off values corresponding to the three screening indicators were 76.15fl,71.95fl,77.35fl,86.15fl,75.41fl,61.15fl;24.35pg,21.51pg,25.45pg,28.65pg,24.01pg,20.51pg;2.45％,3.05％,3.55％,3.25％,2.45％,1.65％,respectively. Conclusion:The levels of MCV,MCH and HbA2 are correlated with the phenotype of thalassemia,and the detection of these indicators is of great significance for the prevention and control of thalassaemia.

Objective:To explore the changes in serum advanced receptor for glycation end-products (sRAGE) and neuregulin-1 (NRG-1) in patients with different conditions of H-type hypertension combined with acute ischemic stroke (AIS) and their relationship with short-term prognosis.Methods:A total of 185 patients with H-type hypertension complicated with AIS admitted to the Linyi Central Hospital from January 2020 to December 2022 were selected and included in the AIS group. According to the National Institutes of Health Stroke Scale (NIHSS) score, there were 55 cases in the mild group (≤4 points), 86 cases in the moderate group (5-20 points), and 44 cases in the severe group (>20 points); According to the improved Rankin scale score, the patients were divided into a poor prognosis group (>2 points) and a good prognosis group (≤2 points). Another 100 healthy individuals who underwent physical examinations during the same period in our hospital were selected as the control group. Enzyme linked immunosorbent assay was used to detect serum sRAGE and NRG-1 levels in subjects. The correlation between serum sRAGE, NRG-1 levels and NIHSS score in patients with H-type hypertension complicated with AIS was analyzed through Spearman test. A multivariate logistic regression model was used to analyze the influencing factors of poor short-term prognosis in patients with H-type hypertension complicated with AIS. The receiver operating characteristic (ROC) curve analysis revealed the predictive value of serum sRAGE and NRG-1 levels for poor short-term prognosis in patients with H-type hypertension complicated with AIS.Results:The serum sRAGE level in the AIS group was higher than that in the control group, while the NRG-1 level was lower than that in the control group (all P<0.05). The serum sRAGE levels of patients in the mild, moderate, and severe groups increased sequentially, while the NRG-1 levels decreased sequentially (all P<0.05). Spearman correlation analysis showed that the NIHSS score was positively correlated with serum sRAGE levels ( rs=0.847, P<0.001) and negatively correlated with serum NRG1 levels ( rs=-0.810, P<0.001) in patients with H-type hypertension and AIS. After 90 days of follow-up, the incidence of poor prognosis in 185 patients with H-type hypertension and AIS was 37.84%(70/185). Multivariate logistic regression model analysis showed that increased age, diabetes, increased NIHSS score, increased homocysteine (Hcy) and increased sRAGE were independent risk factors for poor short-term prognosis of patients with type H hypertension combined with AIS, while increased NRG-1 was an independent protective factor (all P<0.05). ROC curve analysis showed that the combined detection of serum sRAGE and NRG-1 levels predicted a poor short-term prognosis in patients with H-type hypertension and AIS, with an area under the curve (AUC) of 0.876, which was higher than the predicted values of 0.795 and 0.791 for serum sRAGE and NRG-1 levels alone (all P<0.05). Conclusions:Elevated serum sRAGE levels and decreased NRG-1 levels are closely related to worsening of the condition and poor short-term prognosis in patients with H-type hypertension and AIS. The combined detection of serum sRAGE and NRG-1 levels has high predictive value for poor short-term prognosis in patients with H-type hypertension and AIS.