Premature ovarian insufficiency (POI), characterized by the decline of ovarian function before age 40, significantly compromises fertility and long-term health of patients. Stem cell therapy has emerged as a promising approach for POI. This review synthesizes clinical evidence from studies utilizing cells sourced from adult tissues (e.g., adipose derived mesenchymal stem cells, bone marrow mesenchymal stem cells, peripheral blood stem cells) and perinatal tissues (e.g., human amniotic epithelial cells, umbilical cord-derived mesenchymal stem cells). Evidence suggests that stem cell transplantation can improve ovarian reserve, reflected by reduced follicle-stimulating hormone levels and increased estradiol and anti-Müllerian hormone levels, with some patients resuming menstruation and achieving pregnancy. However, treatment efficacy is influenced by patient-specific factors and clinical protocols. Optimizing stem cell transplantation protocols is pivotal for enhancing their clinical efficacy and safety. This article elaborates on key optimization strategies, including transplantation timing, delivery routes, and combination therapies, proposing that early intervention and personalized regimens may improve outcomes. We also discuss patient benefits (such as pregnancy outcomes and quality of life) and treatment safety. Future research should focus on refining personalized strategies, investigating the therapeutic potential of stem cell-derived agents, and establishing long-term follow-up, thereby advancing POI therapy toward precision medicine and standardized application.

OBJECTIVES: This study aimed to analyze the influence of drug factors on the efficacy of bisphosphonate for chronic nonbacterial osteomyelitis to provide a reference for clinical treatment and promote clinical rational drug use by evaluation of effectiveness and safety of bisphosphonate treatment of chronic nonbacterial osteomyelitis. METHODS: Literature on the treatment of chronic nonbacterial osteomyelitis by using bisphosphonate was collected and analyzed from PubMed, Medline, Embase, Cochrane, ISI Web of Knowledge, CNKI, VIP, and Wanfang databases. RESULTS: A total of 489 cases were collected, with an average complete response rate of clinical presentation, laboratory tests and imaging findings of 80.37%, 80.56% and 79.22%, respectively. Except for opadronate, risedronate, ibandronate, pamidronate, alendronate, neidronate and zoledronate showed good efficacy, and the average complete response rates were 100%, 100%, 81.64%, 87.50%, 69.23% and 69.23%, respectively.The study found that in the pamidronate group, the average complete response rate of 0.5-1 mg/kg (maximum single dose≤60 mg) subgroup and the frequency of administration once every 3 months subgroup were better than other subgroups. CONCLUSIONS Bisphosphonate could be used to treat chronic nonbacterial osteomyelitis, which of efficacy were affected by different drug types, dose and frequency of administration. The optimal dose and frequency of administration of pamidronate were 0.5-1 mg/kg (maximum single dose≤60 mg) and once every 3 months, respectively.
Osteomyelitis/drug therapy* ; Humans ; Diphosphonates/administration & dosage* ; Chronic Disease ; Bone Density Conservation Agents/administration & dosage* ; Female ; Pamidronate ; Middle Aged ; Male

Objective:To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury.Methods:Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ2 test or t-test was used for statistical analysis. Results:Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference ( χ2 ?=?9.975 0, P ?=?0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference ( χ2 ?= 0.593 5, P ?=?0.441 1). Conclusion:Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.

Objective:To identify and screen the differential methylation genes in patients with cholangiocarcinoma and to predict the prognosis of patients with CCA.Methods:Cholangiocarcinoma tissues and paracancerous tissues of 8 patients with cholangiocarcinoma in Fujian Provincial Hospital from October 2019 to May 2020 were selected for 850K methylation sequencing analysis to obtain differentially methylated genes. The 2018 genome-wide methylation data and clinical information of 36 patients with cholangiocarcinoma were download from The Cancer Genome Atlas (TCGA) database, the 2012 cholangiocarcinoma methylation data (GSE32879) were download from the Gene Expression Omnibus (GEO) database, and the 2018 TCGA database differential survival genomic data of overall survival (OS) and disease-free survival (DFS) of cholangiocarcinoma were download from the GEPIA2 database. The differentially methylated positions (DMP) and differentially methylated regions (DMR) results of 850K methylation sequencing analysis of submitted samples, methylated genes in TCGA and GEO databases, and cholangiocarcinoma survival genes of samples were jointly submitted for testing, multi-data set analysis was performed by the Sangerbox VENN tool, and common differentially methylated genes were obtained by intersection screening. The minimum P value method was used to determine the cut-off value of gene expression in Sangerbox, and the patients were divided into high and low expression groups of differentially methylated genes. The OS, DFS, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI) of cholangiocarcinoma patients were compared between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Results:A total of 121 954 DMP were identified by 850K methylation sequencing of cholangiocarcinoma tissues and paracancerous tissues of 8 patients; a total of 1 399 differentially methylated genes were identified in DMR, and the common prognosis related genes glucosaminyl (N-acetyl) transferase 1 (GCNT1) and neurotrophic receptor tyrosine kinase 3 (NTRK3) were identified by intersection identification. The expression of GCNT1 in the cholangiocarcinoma tissues was higher than that in the paracancerous tissues, and the difference was statistically significant ( P = 0.040). The expression of NTRK3 in cholangiocarcinoma tissues was higher than that in the paracancerous tissues, but the difference was not statistically significant ( P = 0.790). The minimum P value method was used to predict the prognosis of patients with cholangiocarcinoma based on the combined expression of GCNT1 and NTRK3, and the order was based on the sum of the expression levels of the two genes. When 30% of the ranking was taken as the cut-off value, the difference in DFS between the high expression group and the low expression group in cholangiocarcinoma was the most significant ( P < 0.001); there was no significant difference in OS between the two groups ( P = 0.065). The results of GO functional analysis showed that GCNT1 was involved in protein glycosylation, macromolecule glycosylation, glycosylation, glycoprotein biosynthetic process, glycoprotein metabolic process, transferase activity and transferring glycosyl groups, protein O-linked glycosylation, O-glycan processing, etc., and NTRK3 was involved in neurotrophin signaling pathway, Ras signaling pathway, EGFR tyrosine kinase inhibitor resistance, ErbB signaling pathway, phospholipase D signaling pathway, central carbon metabolism in cancer, natural killer cell mediated cytotoxicity, etc. The results of KEGG analysis showed that GCNT1 was mainly associated with system functions such as mucin-type O-glycan biosynthesis and metabolic pathways, and NTRK3 was mainly associated with cell surface receptor pathways, intracellular signal transduction, positive regulation of stimulatory responses, transmembrane receptor protein tyrosine kinase signaling pathway, enzyme-linked receptor protein signaling pathway, MAPK signaling pathway cascade and regulation, protein phosphorylation signal transduction and other system functions. Conclusions:The expressions of differentially methylated genes GCTNT1 and NTRK3 in cholangiocarcinoma have certain predictive effects on the prognosis of patients with cholangiocarcinoma.

ObjectiveTo explore the influence of the core symptoms of attention deficit hyperactivity disorder （ADHD） on behavioral problems of children with ADHD propensity， so as to provide references for early identification and targeted intervention for children with ADHD propensity. MethodsFrom July to August 2021， 25 children with ADHD propensity were screened as the ADHD propensity group， and 25 children matched for age， gender and grade were included as the normal group in an elementary school in Guangzhou. ADHD core symptoms were assessed by the Chinese version of the Swanson Nolan and Pelham， version IV-parent form for ADHD （SNAP-IV）， and behavioral problems were assessed by Questionnaire-Children with Difficulties （QCD） and Conners Parental Symptom Questionnaire （PSQ）. Spearman correlation analysis was used to examine the correlation between ADHD core symptoms and QCD and PSQ scores， and hierarchical linear regression analysis was used to explore the effect of ADHD core symptoms on behavioral problems. Results① The differences between the groups showed that both attention deficit and hyperactivity-impulsivity factor scores were higher in the ADHD propensity group than those in the normal group （t=7.771， 6.726， P<0.01）. ② Correlation analysis showed that the attention deficit factor score was negatively correlated with QCD total score （r=-0.440， P<0.05）， and positively correlated with the learning problem factor score of PSQ （r=0.457， P<0.05）. The score of hyperactivity-impulsivity was negatively correlated with score of anxiety factor in PSQ （r=-0.457， P<0.05）， and positively correlated with impulse-hyperactivity factor score （r=0.552， P<0.01）. ③ Hierarchical linear regression analysis showed that the attention deficit factor score negatively predicted the total score of QCD （B=-0.682， P<0.05， R²=0.468）. The hyperactivity-impulsivity factor score had a negative predictive effect on the anxiety factor score of PSQ （B=-0.048， P<0.05， R²=0.367）， and had a positive predictive effect on the impulsivity-hyperactivity factor score （B=0.077， P<0.01， R²=0.424）. ConclusionChildren with ADHD propensity have significant attention deficit symptoms， hyperactivity-impulsivity symptoms and behavioral problems， and the attention deficit may be the main cause of their daily behavioral problems， while hyperactivity-impulsivity may be the main cause of their impulsive-hyperactivity problems.

Objective:To investigate the effect of natural hyperoxic environment on liver lipid metabolism and liver function based on the bile acid-farnesoid X receptor pathway in sub-healthy rats.Methods:Forty adult male Wistar rats were randomly divided into control group ( n = 10) and sub-healthy model group ( n = 30). The control group was fed a normal diet, and the model group was fed a high-fat-sugar diet with limited daily activities for 5 weeks. The sub-healthy model was successfully established and the feeding conditions were restored. The hyperoxic intervention group (healthy group) were placed in a natural hyperoxic environment for 7 days. The rats feeding status in the spontaneous recovery group were unchanged. The appearance and exhaustive swimming time were compared before and after in healthy rats. Peripheral blood was collected for biochemical measurement. The fluorescence intensity of FXR and peroxisome proliferator activated receptor α (PPAR α) in liver tissue was detected by fluorescence double staining. Real-time fluorescent semi-quantitative PCR and Western blot were used to detect the RNA and protein expression condition of bile acid-FXR signaling pathway related indicators (FXR, PPARα, and SREBP-1c) in liver tissues. Results:Compared with the control group, the model group had gained body weight, and the vitality was decreased, while triglycerides [TG, (1.18 ± 0.20) mmol/L vs. (0.65 ± 0.12) mmol/L] and total cholesterol [TC, (1.23 ± 0.29) mmol/L vs. (1.00 ± 0.25) mmol/L] level was increased, ( P < 0.05), which suggests the presence of hepatic steatosis. TG and TC level in the healthy group and spontaneous recovery group were lower than the model group, and the differences between the healthy group and the model group were statistically significant ( P < 0.05). Compared with the model group, the expression of FXR and PPARα in the liver of the healthy and the spontaneous recovery group was enhanced, while the expression of the sterol regulatory element binding protein 1c (SREBP-1c) was decreased. FXR and PPARα mRNA levels in the healthy group and the model group were (9.27 ± 0.26 vs. 6.77 ± 0.20), and (9.71 ± 0.21 vs. 7.09 ± 0.24), P < 0.01, respectively. Compared with the model group, spontaneous recovery group mRNA levels were 7.99 ± 0.30 and 8.44 ± 0.28, P < 0.05, respectively. FXR and SREBP-1c protein levels between the healthy group and the model group were (1.30 ± 0.19 vs.0.43 ± 0.28), and (1.56 ± 0.22 vs. 2.43 ± 0.19), P < 0.01, respectively. Compared with the model group, the FXR and SREBP-1c protein levels of the spontaneous recovery group were 0.81 ± 0.33 vs. 2.10 ± 0.38, P < 0.05, respectively. In addition, natural hyperoxic environment had enhanced liver lipid metabolism and improved lipid disorders. Conclusion:The natural hyperoxic environment have the ability to regulate liver lipid metabolism and can improve mild hyperlipidemia to a certain extent.

The Lianhua Qingwen (LHQW) capsule is a popular traditional Chinese medicine for the treatment of viral respiratory diseases.In particular,it has been recently prescribed to treat infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However,due to its complex composi-tion,little attention has been directed toward the analysis of chemical constituents present in the LHQW capsule.This study presents a reliable and comprehensive approach to characterizing the chemical constituents present in LHQW by high-performance liquid chromatography-Q Exactive-Orbitrap mass spectrometry (HPLC-Q Exactive-Orbitrap-MS) coupled with gas chromatography-mass spectrometry(GC-MS).An automated library alignment method with a high mass accuracy (within 5 ppm) was used for the rapid identification of compounds.A total of 104 compounds,consisting of alkaloids,flavonoids,phenols,phenolic acids,phenylpropanoids,quinones,terpenoids,and other phytochemicals,were suc-cessfully characterized.In addition,the fragmentation pathways and characteristic fragments of some representative compounds were elucidated.GC-MS analysis was conducted to characterize the volatile compounds present in LHQW.In total,17 compounds were putatively characterized by comparing the acquired data with that from the NIST library.The major constituent was menthol,and all the other compounds were terpenoids.This is the first comprehensive report on the identification of the major chemical constituents present in the LHQW capsule by HPLC-Q Exactive-Orbitrap-MS,coupled with GC-MS,and the results of this study can be used for the quality control and standardization of LHQW capsules.

Isomalto-oligosaccharides (IMO) have good physiochemical properties and excellent physiological functions to make it widely used in food, medicine, feed, cosmetics and other industries. However, the procedures for industrial production of IMO are complicated. Therefore, it is necessary to develop an economical and easy-to-operate method. The genes encoding for β-amylase and α-transglucosidase were fused and co-displayed on the yeast cell surface of Yarrowia lipolytica which can convert liquefied starch to IMO in one step. The highest IMO purity of 75.3% was obtained using the displayed fusion-enzyme at 50 °C. This method showed potential application in IMO production.
Oligosaccharides ; Starch ; Yarrowia ; beta-Amylase

Objective To explore the effects of morroniside on the expression of CD34 in ipsilateral cortex of rats after focal cerebral isch-emia-reperfusion. Methods 45 male Sprague-Dawley rats were divided into sham group (n=9), ischemia group (n=9), and morroniside groups (low, medium and high dosage groups, n=9). The middle cerebral artery were occluded for 30 minutes, and reperfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg, 270 mg/kg after operation. The expression of CD34 in the isch-emic ipsilateral cortex were detected with immunohistochemistry (n=6) and Western blotting (n=3) 7 days after operation. Results The ex-pression of CD34 increased in the ischemia group compared with the sham group, and further increased in the morroniside groups of high dos-age compared with the ischemia group (F>14.865, P<0.001). Conclusion Morroniside could increase the expression of CD34 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, which may promote the angiogenesis and neurogenesis after ischemia.