The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insecticides (NNI). METHODS: Fifteen C57BL/6 male mice were randomly divided into control group (CTRL group), exposure group (NNI group) and Lactobacillus intervention group (NNI-L group). The mice in CTRL group were given 0.02ml/g of 0.5% carboxymethyl cellulose sodium solution by gavage for 14 days. The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days. The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5×108cfu/ml of Lactobacillus reuteri powder solution for 14 days. Then, the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining, immunofluorescence staining and RNA sequencing. RESULTS: Compared with CTRL group, the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner. And the decline in the number of spermatogenic cells and sperm was observed. And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group. The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequencing, with significant down-regulation being found in NPFF and IGF2. While the expression of HSD3B8 was significantly up-regulated. The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri. CONCLUSION Testicular spermatogenesis and endocrine function can be damaged by NNI exposure. And oral administration of Lactobacillus reuteri protects testis from the adverse effects of NNI toxicity.
Animals ; Male ; Limosilactobacillus reuteri ; Testis/pathology* ; Mice ; Mice, Inbred C57BL ; Insecticides/toxicity* ; Neonicotinoids/toxicity* ; Probiotics ; Spermatogenesis/drug effects*

OBJECTIVE: To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele（VC）with male infertility. METHODS: A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis. The patients were divided into the microscopic group (180 cases) and laparoscopic group (127 cases) according to the surgery method. The pre- and postoperative clinical data of these two groups were analyzed, including the degree of dilatation and reflux time of internal spermatic vein，hemodynamic parameters of testicular capsular artery，proportion of progressive motility spermatozoa (PR), concentration of spermatozoa, proportion of normal morphology sperm，the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively. RESULTS: All the surgeries for the 307 patients in this study were successful. There was no significant difference in operation time, hospitalization time and management expenses between the microscopic group and the laparoscopic group (P>0.05). Compared to the patients in laparoscopic group, the patients in the microscopic group received a better improvement in venous diameter, reflux time of spermatic veins and hemodynamic parameters of testicular capsular artery (P<0.05). Moreover, the semen analysis showed that the PR, spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group (P<0.05). During the 2-year follow-up period, the conception rate of spouses in the microscopic group was 67.2%, while only 47.2% in the laparoscopic group, in which the difference was statistically significant (P<0.05). Besides, the time-to-pregnancy ( TTP ) within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group（P<0.05). Meanwhile, the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group (P<0.05). It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group (P<0.05). Severe complication such as testicular atrophy, bleeding and infection did not appear in both of two groups. However, the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group (P<0.05). CONCLUSION Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility. But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters, semen quality, pregnancy outcome and postoperative complications, which is worthy of further clinical applications.
Humans ; Male ; Varicocele/complications* ; Laparoscopy ; Infertility, Male/etiology* ; Retrospective Studies ; Adult ; Microsurgery ; Treatment Outcome ; Pregnancy ; Female

Aim To explore the effect of ginsenoside Rg3 on the biological behavior of human gastric cancer SGC-7901 cells by regulating E2F1.Methods MTT assay was used to determine the effect of ginsenoside Rg3(0,80,160,320 μmol·L-1)on cell prolifera-tion.The effects of different concentrations of ginsen-oside Rg3 on apoptosis were measured by flow cytome-try.The effects of different concentrations of ginsen-oside Rg3 on cell migration and invasion were deter-mined by scratch healing experiment and Transwell ex-periment.The effects of different concentrations of gin-senoside Rg3 on the expression of E2F1,MMP-2,MMP-9,BCL-2 and Bax were determined by Western blot.Results Compared with the blank control group,the cell survival rate of 80,160 and 320 μmol ·L-1 ginsenoside Rg3 group was significantly lower,and it was concentration-dependent(P＜0.05).Com-pared with the blank control group,the apoptosis rate of 80,160 and 320 μmol·L-1 ginsenoside Rg3 group significantly increased in a concentration-dependent manner(P＜0.05).Compared with the blank control group,the number of cell migration in 80,160 and 320 μmol·L-1 ginsenoside Rg3 groups was significantly lower in a concentration-dependent manner(P＜0.05).Compared with the blank control group,the number of cell invasion in 80,160 and 320 μmol· L-1 ginsenoside Rg3 groups was significantly lower in a concentration-dependent manner(P＜0.05).The E2F1 mRNA and E2F1 protein expression in the 80,160,and 320 μmol·L-1 ginsenoside Rg3 groups were significantly reduced in a concentration-dependent manner compared with that in the blank control group(P＜0.05).The protein expression of MMP-2,MMP-9,and BCL-2 in the cells of 80,160,and 320 μmol ·L-1 ginsenoside Rg3 group significantly decreased compared with those of the blank control group,and BCL-2 significantly increased compared with that of the blank control group in a concentration-dependent man-ner(P＜0.05).Conclusions Ginsenoside Rg3 can reduce the proliferation,inhibit the migration and inva-sion of gastric cancer SGC-7901 cells,and promote the apoptosis of SGC-7901 cells in a concentration-depend-ent manner,and its mechanism may be related to the down-regulation of MMP-2,MMP-9,and BCL-2 ex-pression and up-regulation of Bax expression through E2F1.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To analyze the medication rules of national patented Chinese herbal compounds for the treatment of diabetic peripheral neuropathy(DPN)by data mining method,and to provide reference for clinical medication.Methods The patents of Chinese medicine compound for the treatment of DPN were retrieved from the website of the China National Intellectual Property Administration(CNIPA).Excel 2021 was used for frequency statistics.RAW Graphs 2.0 was used to make a Sankey diagram of the efficacy of high-frequency Chinese medicinals.SPSS Statistics 25.0 software was used for hierarchical cluster analysis of the medicines,and the core prescriptions were mined based on Cytoscape 3.9.1.Results A total of 101 patented prescription were included,involving 243 herbs.The top three Chinese medicines in the descending order of occurrence frequency were Salviae Miltiorrhizae Radix et Rhizoma,Astragali Radix,and Paeoniae Radix Alba.Most of the medicines of patented Chinese medicine compounds for the treatment of DPN were warm and mild in nature,sweet,bitter and pungent in flavor,and had the meridian tropism of liver,heart and spleen meridians.According to the therapeutic actions,the medicine can be divided into tonic drugs,blood-activating and stasis-removing drugs,exterior-releasing drugs,liver-calming and wind-extinguishing drugs,heat-clearing drugs,bleeding-arresting drugs,mind-calming drugs,and urination-promoting and dampness-percolating drugs.The association rule analysis revealed the drug combination of Astragali Radix and Angelicae Sinensis Radix with the highest support.After hierarchical cluster analysis,the top 31 Chinese medicinals were classified into 7 groups.The core prescription which was composed of 7 medicines,namely Astragali Radix,Chuanxiong Rhizoma,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Achyranthis Bidentatae Radix,Cinnamomi Ramulus and Angelicae Sinensis Radix was finally mined out.Conclusion The treatment of DPN with patented Chinese herbal compounds is based on the therapies of supplementing deficiency,activating blood and removing stasis,and warming and unblocking meridians and collaterals.Meanwhile,consolidating the acquired foundation by strengthening spleen and soothing liver is also stressed.Clinically,the herbal pairs of Astragali Radix-Angelicae Sinensis Radix,Paeoniae Radix Alba-Salviae Miltiorrhizae Radix et Rhizoma are the optional drugs,and the core prescription composed of Astragali Radix,Chuanxiong Rhizoma,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Achyranthis Bidentatae Radix,Cinnamomi Ramulus and Angelicae Sinensis Radix can be used for the whole course of DPN.

Objective To explore the applicability and optimal cut-off of the revised Cubbin & Jackson scale in the diagnosis of pressure injury in ICU patients in China.Methods From April 2021 to October 2022,6 203 ICU patients from 35 tertiary hospitals in Gansu Province were included in the study by convenience sampling method.The standardized trained ICU nurses examined the skin and collected relevant data,determined whether or not there was pressure injury and its stage,and simultaneously used the revised Cubbin & Jackson scale for pressure injury risk assessment.The software was used to statistically analyze the area under the receive operating characteristic curve(AUC),Yoden index,sensitivity,specificity and other indexes of the revised Cubbin & Jackson scale in the diagnosis of pressure injury in ICU patients.Results A total of 79 cases of pressure injury occurred during hospitalization in 6 203 ICU patients,with an incidence of 1.27％.Hierarchical analysis showed that the AUC of the revised Cubbin & Jackson scale in the prediction and diagnosis of pressure injury ranged from 0.74 to 0.92 in ICU patients with different sex,age,length of ICU stay,whether or not mechanically ventilated,and whether or not surgical.The Yoden index,sensitivity and specificity were 0.40-0.74,77.27％-94.44％and 62.44％-82.63％,respectively.When the total score was ≤28 points,the revised Cubbin & Jackson scale obtained the highest AUC(0.86),and the Yoden index,sensitivity,specificity,positive predictive value,negative predictive value,positive likelihood ratio,and negative likelihood ratio were 0.60,92.41％,67.26％,3.50％,99.86％,2.82 and 0.11,respectively.Conclusion The revised Cubbin & Jackson scale can be used as a suitable tool to effectively predict and diagnose pressure injury in ICU patients in China,and the optimal cut-off of ≤28 points is appropriate.

Objective To develop"guideline for risk assessment and prevention of noninvasive ventilation related facial pressure injuries in adults"and to provide a reference for clinical medical staff to evaluate and prevent noninvasive ventilation related facial pressure injuries.Methods Referring to the"WHO Guideline Development Manual",clinical problems were formed through 3 rounds of Delphi expert consultation.The relevant recommendation opinions and evidence were screened,extracted,integrated and evaluated to form a draft consensus.Through a round of Delphi expert consultation and a round of expert consensus meeting,expert opinions were combined to modify and improve the content of each item to form a final draft of the expert consensus.Results Recommendations for the constructed guideline included 7 aspects of risk factors,high-risk sites,assessment tools,assessment timing and content,selection of non-invasive ventilation equipment,selection of dressings,and preventive measures,including 7 clinical questions and 15 recommendations.Conclusion The"guideline for risk assessment and prevention of noninvasive ventilation related facial pressure injuries in adults"was an evidence-based guideline based on the best evidence,Chinese clinical reality,and professional judgment,and it can provide practice bases for scientific clinical decisions making by clinical medical staff and managers.