AIM:To study the mechanism of oxy-sophoridine(OSR)in relieving neuropathic pain(NP).METHODS:The analgesic effect of OSR was observed by measuring mechanical pain sensitivity.By combining OSR with agonists and antagonists re-lated to synthesis and metabolism of gamma ami-nobutyric acid(GABA),the mechanism related to analgesic effects of OSR and GABA nervous system is studied.The expression of c-Fos immunopositive cells and the expression of c-Fos and Glutamic acid decarboxylase(Glutamic acid decarboxylase 67)in brain and spinal cord were detected by immunoflu-orescence staining.Co-expression of GAD67,GABA transporter 1(gamma-Aminobutyric acid Transport-er 1,GAT-1)immunopositive cells.RESULTS:Com-pared with Sham group,spared nerve injury(SNI)group showed increased mechanical pain sensitivi-ty,increased expression of c-Fos immunopositive cells,decreased and increased co-expression of c-Fos and GAD67 and GAT-1 immunopositive cells,re-spectively.Compared with SNI group,mechanical algesia in OSR 500 and 1 000 mg/kg groups was de-creased,algesia in OSR 250 mg/kg combined with antagonist group was decreased,and algesia in OSR 500 mg/kg combined with agonist group was increased.The co-expression of c-Fos and GAD67 immunopositive cells in the brain and spinal cord of OSR 500 mg/kg group increased,while the co-ex-pression of c-Fos and GAT-1 decreased.CONCLU-SION:OSR has a good analgesic effect on NP mice induced by SNI.The mechanism is that OSR increas-es the content of central GABA by up-regulating GABAergic neurons in brain and spinal cord.

Objective : To investigate the effect of solasonine regulation of the STAT3 signaling pathway on the bio- logical behavior of lung adenocarcinoma cells． Methods : H1299 cells were treated with 0. 125，0. 25，0. 5 and 0. 75 mmol /L solasonine，respectively．The proliferative activity of H1299 cells was detected by CCK-8．The mi- gration and invasion ability of H1299 cells were detected by scratch，Transwell migration and invasion assay．The apoptosis level of H1299 cells was detected by flow cytometry and Hoechest 33258 /PI double staining．The protein expression levels of STAT3，p-STAT3 ，Bcl-2 ，Bax ，Caspase-3 ，Cl-Caspase-3 ，Snail ，Slug ，N-cadherin and E- cadherin in H1299 cells were detected by Western blot assay． Results: Solasonine at different concentrations sig- nificantly reduced the proliferation of H1299 cells (P＜0. 05) ．0. 125 and 0. 25 mmol /L solasonine promoted the apoptosis of H1299 cells (P＜0. 05) and inhibited the migration and invasion of H1299 cells (P＜0. 05) ．Solaso- nine inhibited the expression of STAT3，p-STAT3 and Bcl-2 proteins，enhanced the expression of Bax，Caspase-3 and Cl-Caspase-3 proteins．Solasonine inhibited the activation of STAT3 in cells，reduced Snail and Slug protein expression levels，enhanced E-cadherin，reduced N-cadherin(P＜0. 05) ． Conclusion Solasonine can inhibit the activation of STAT3 ，activate the Bcl-2 /Bax / Caspase3 apoptosis pathway ，inhibit the continuous proliferation of lung adenocarcinoma H1299 cells，and promote the apoptosis of lung adenocarcinoma H1299 cells．Meanwhile，it can inhibit the activation of STAT3，reduce the expression of Snail / Slug protein，affect the EMT transformation of lung adenocarcinoma H1299 cells，and inhibit the migration and invasion of lung adenocarcinoma H1299 cells．

Forty adult male C57BL/6 mice were randomly divided into four groups:the control group,Salmonella typhimurium(S.typhimurium)(ST)group,phlorizin(PHZ)+S.typhimuri-um(ST)group,and PHZ(80 mg/kg)group,with 10 mice in each group.Morphological observa-tion,HE staining,ELISA,immunofluorescence and Western blot were performed,the results showed that PHZ significantly increased the cecal index,decreased the spleen index of S.typhi-murium-induced mice(P＜0.05),and reduce the pathological damage of cecum in mice.Mean-while,PHZ treatment also significantly reduced colonization of S.typhimurium in the cecum,spleen,mesenteric lymph nodes and liver(P＜0.05).The results of ELISA showed that PHZ treatment also significantly inhibited the S.ty phimurium-induced increase in the expression of IL-1β,INF-γ,TNF-a and IL-6 in the cecum of mice(P＜0.05).Immunofluorescence and Western blot results showed that PHZ significantly increased the protein expression levels of Occludin,Claudin-3,and ZO-1 in the cecal barrier of mice induced by S.typhimurium(P＜0.05).These results con-firmed that phlorizin could improve cecal inflammation and intestinal barrier damage induced by S.typhimurium in mice.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a child with Acid-labile subunit deficiency (ALS). METHODS: A male child diagnosed with ALS at Dongguan Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Clinical data of his family was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and Sanger sequencing was used for family verification of candidate variants. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was classified. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2020-6). RESULTS: The patient, a 5-year-and-7-month-old boy, presented with short stature and delayed bone age. Endocrine examinations showed decreased serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP3). WES revealed that he has harbored compound heterozygous variants of the IGFALS gene, namely c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31. Sanger sequencing verified that the variants were inherited from his father and mother, respectively. According to the ACMG guidelines, c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 variants were classified as likely pathogenic (PVS1+PM2_supporting). Based on the pre-set literature search strategy, 11 research literature on ALS were retrieved, which involved a total of 33 families and 62 patients. Combined with the patient in this study, 31 IGFALS gene variants were identified among the 63 patients, which mainly consisted of missense variants (20 types), with variant sites concentrated in exon 2. The main clinical features were short stature in conjunct with delayed puberty, with a significant genotype-phenotype correlation. CONCLUSION The IGFALS gene variants NM_004970.2: c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 may be the genetic etiology in this family. This study has expanded the variant spectrum of the IGFALS gene and provided valuable information for the diagnosis, genetic counseling and clinical treatment of the disease.
Humans ; Male ; Phenotype ; Child, Preschool ; Carrier Proteins/genetics* ; Glycoproteins/deficiency* ; Exome Sequencing ; Female ; Mutation ; Insulin-Like Growth Factor I/metabolism* ; Growth Disorders/genetics*

Forty adult male C57BL/6 mice were randomly divided into four groups:the control group,Salmonella typhimurium(S.typhimurium)(ST)group,phlorizin(PHZ)+S.typhimuri-um(ST)group,and PHZ(80 mg/kg)group,with 10 mice in each group.Morphological observa-tion,HE staining,ELISA,immunofluorescence and Western blot were performed,the results showed that PHZ significantly increased the cecal index,decreased the spleen index of S.typhi-murium-induced mice(P＜0.05),and reduce the pathological damage of cecum in mice.Mean-while,PHZ treatment also significantly reduced colonization of S.typhimurium in the cecum,spleen,mesenteric lymph nodes and liver(P＜0.05).The results of ELISA showed that PHZ treatment also significantly inhibited the S.ty phimurium-induced increase in the expression of IL-1β,INF-γ,TNF-a and IL-6 in the cecum of mice(P＜0.05).Immunofluorescence and Western blot results showed that PHZ significantly increased the protein expression levels of Occludin,Claudin-3,and ZO-1 in the cecal barrier of mice induced by S.typhimurium(P＜0.05).These results con-firmed that phlorizin could improve cecal inflammation and intestinal barrier damage induced by S.typhimurium in mice.

Objective To investigate the effects of a continuous-dose administration versus different dosage regimens of polyethylene glycol electrolyte solution(PEG)taken in two doses with a 12-hour interval on bowel cleansing efficacy,with the goal of optimizing bowel preparation protocols and improving patient tolerability.Methods 232 patients who underwent painless colonoscopy and used PEG as a bowel cleanser from June 2024 to September 2024 were selected as study subjects.Participants were divided into three groups:the control group(3.00 L PEG continuous dose),experimental group A(0.75 L+2.25 L PEG),and experimental group B(1.50 L+1.50 L PEG).All patients underwent painless colonoscopy within 4～6 h after completing PEG intake.The interval between the two doses of PEG in group A and group B was 12 h.The bowel cleansing efficacy was assessed by using the Boston bowel preparation scale(BBPS),and the rates of colon polyp detection,adverse reactions,sleep duration,and tolerability were recorded.Results There were no significant statistical differences in BBPS scores and colon polyp detection rates among the three groups(P>0.05).Experimental group B experienced the least adverse reactions,followed by experimental group A,while the control group reported the most significant adverse reactions(P<0.05).The timing of PEG administration did not have a significant impact on sleep duration among the three groups(P>0.05).Patients in experimental group B showed good tolerability to PEG and were willing to accept this bowel preparation regimen,followed by group A,while the control group exhibited the poorest tolerability,with significant statistical differences among the three groups(P<0.05).Conclusion The continuous administration and divided administration of PEG have no significant impact on the effectiveness of intestinal cleansing and the detection rate of colonic polyps.However,the divided PEG regimen with a 12 h interval results in fewer adverse reactions and better tolerance,especially the optimal regimen of taking 1.50 L PEG in two doses with a 12 h interval.

Objective To investigate the effects of a continuous-dose administration versus different dosage regimens of polyethylene glycol electrolyte solution(PEG)taken in two doses with a 12-hour interval on bowel cleansing efficacy,with the goal of optimizing bowel preparation protocols and improving patient tolerability.Methods 232 patients who underwent painless colonoscopy and used PEG as a bowel cleanser from June 2024 to September 2024 were selected as study subjects.Participants were divided into three groups:the control group(3.00 L PEG continuous dose),experimental group A(0.75 L+2.25 L PEG),and experimental group B(1.50 L+1.50 L PEG).All patients underwent painless colonoscopy within 4～6 h after completing PEG intake.The interval between the two doses of PEG in group A and group B was 12 h.The bowel cleansing efficacy was assessed by using the Boston bowel preparation scale(BBPS),and the rates of colon polyp detection,adverse reactions,sleep duration,and tolerability were recorded.Results There were no significant statistical differences in BBPS scores and colon polyp detection rates among the three groups(P>0.05).Experimental group B experienced the least adverse reactions,followed by experimental group A,while the control group reported the most significant adverse reactions(P<0.05).The timing of PEG administration did not have a significant impact on sleep duration among the three groups(P>0.05).Patients in experimental group B showed good tolerability to PEG and were willing to accept this bowel preparation regimen,followed by group A,while the control group exhibited the poorest tolerability,with significant statistical differences among the three groups(P<0.05).Conclusion The continuous administration and divided administration of PEG have no significant impact on the effectiveness of intestinal cleansing and the detection rate of colonic polyps.However,the divided PEG regimen with a 12 h interval results in fewer adverse reactions and better tolerance,especially the optimal regimen of taking 1.50 L PEG in two doses with a 12 h interval.

AIM:To study the mechanism of oxy-sophoridine(OSR)in relieving neuropathic pain(NP).METHODS:The analgesic effect of OSR was observed by measuring mechanical pain sensitivity.By combining OSR with agonists and antagonists re-lated to synthesis and metabolism of gamma ami-nobutyric acid(GABA),the mechanism related to analgesic effects of OSR and GABA nervous system is studied.The expression of c-Fos immunopositive cells and the expression of c-Fos and Glutamic acid decarboxylase(Glutamic acid decarboxylase 67)in brain and spinal cord were detected by immunoflu-orescence staining.Co-expression of GAD67,GABA transporter 1(gamma-Aminobutyric acid Transport-er 1,GAT-1)immunopositive cells.RESULTS:Com-pared with Sham group,spared nerve injury(SNI)group showed increased mechanical pain sensitivi-ty,increased expression of c-Fos immunopositive cells,decreased and increased co-expression of c-Fos and GAD67 and GAT-1 immunopositive cells,re-spectively.Compared with SNI group,mechanical algesia in OSR 500 and 1 000 mg/kg groups was de-creased,algesia in OSR 250 mg/kg combined with antagonist group was decreased,and algesia in OSR 500 mg/kg combined with agonist group was increased.The co-expression of c-Fos and GAD67 immunopositive cells in the brain and spinal cord of OSR 500 mg/kg group increased,while the co-ex-pression of c-Fos and GAT-1 decreased.CONCLU-SION:OSR has a good analgesic effect on NP mice induced by SNI.The mechanism is that OSR increas-es the content of central GABA by up-regulating GABAergic neurons in brain and spinal cord.

Objective:To investigate the therapeutic effect of naringenin on diabetes retinopathy (DR) rats by regulating Janus kinase 2 (JAK2) /signal transducer and activator of transcription 3 (STAT3) /suppressor of cytokine signaling 1 (SOCS1) signaling pathway.Methods:A DR rat model was constructed and randomly separated into DR group, naringenin group, activator group, and naringenin+activator group, with normal rats as the control group. After intervention according to corresponding groups, blood glucose and glycosylated hemoglobin of rats were detected. Retinal tissue was separated, and interleukin-6 (IL-6), IL-1β, glutathione (GSH), and catalase (CAT) were detected. The pathological changes in rats and blood retinal vascular barrier permeability were detected, and the retinal tissue adhesion factor 1 (VCAM-1), anti vascular endothelial growth factor (VEGF) mRNA, and JAK2/STAT3/SOCS1 pathway related proteins were detected.Results:In the control group, blood glucose levels were (5.16±0.53) mmoL, glycosylated hemoglobin (4.26±0.45) %, IL-6 (63.11±6.35) pg/mL, IL-1β (23.11±2.38) pg/mL, Evans blue (EB) content (4.72±0.49) ng/mg, VCAM-1 (1.02±0.11), VEGF mRNA expression (0.93±0.10), p-JAK2/JAK2 (0.24±0.03), p-STAT3/STAT3 (0.19±0.02), GSH (17.62±1.81) nmoL/mg, CAT (11.68±1.19) IU/mg, and SOCS1 expression 1.44±0.16; while in DR group, blood glucose were (18.85±1.89) mmoL, HBA1c (11.62±1.18) %, IL-6 (89.17±8.99) pg/mL, IL-1β (52.11±5.28) pg/mL, EB (10.24±1.08) ng/mg, VCAM-1 1.56±0.16, VEGF 1.61±0.18, P-JAK2/JAK2 0.55±0.06 and P-STAT3/STAT3 0.47±0.05, all decreased compared with that of the control group ( P<0.05). The expressions of GSH were (8.27±0.88) nmoL/mg, CAT (6.85±0.71) IU/mg and SOCS1 0.86±0.09 in group DR, all increased compared with those of the control group ( P<0.05). In naringin group, blood glucose was (13.11±1.34) mmoL, HBA1c (7.36±0.76) %, IL-6 (67.08±6.75) pg/mL, IL-1β (31.61±3.22) pg/mL, EB content was (6.15±0.63) ng/mg, VCAM-1 1.15±0.12, VEGF mRNA expression 1.17±0.12, P-JAK2 /JAK2 0.29±0.03, and P-STAT3 /STAT3 0.21±0.03, all lower than those in DR Group ( P<0.05). However, the expressions of GSH were (15.22±1.59) nmoL/mg, CAT (10.95±1.11) IU/mg, and SOCS1 (1.37±0.15) ,all higher than those of DR group ( P<0.05). The activator reversed the protective effect of naringenin on DR Rats. Conclusion:Naringenin improves DR rat injury by regulating the JAK2/STAT3/SOCS1 signaling pathway.

Objective : To investigate the effects of immunoglobulin gene superfamily 10 (IGSF10) on prolifera- tion，migration and invasion of lung adenocarcinoma cells． Methods : ioinformatics was applied to study the ex- pression levels of IGSF10 in tumor tissues and normal tissues． Western blot and quantitative real-time PCR ( qPCR) were used to detect the expression level of IGSF10 in lung adenocarcinoma cell lines and normal lung epi- thelial cells．Knockdown of IGSF10，the effect of knockdown of IGSF10 on proliferation，migration and invasion of lung adenocarcinoma A549 cells was examined using cell counting kit-8 ( CCK-8) ，Transwell migration and inva- sion assay，scratch assay and plate cloning assay．The effects of knockdown of IGSF10 on the expression of invasion and migration-related genes in A549 cells were examined by Western blot and qPCR assays. Results : IGSF10 ex- pression in lung adenocarcinoma tissues was lower than that in normal tissues (P ＜0. 05) ．IGSF10 expression in lung adenocarcinoma cell lines was lower than that in lung epithelial cells (P＜0. 05) ．Knockdown of IGSF10 pro- moted the ability of lung adenocarcinoma A549 cells to proliferate ，proliferation ，migration and invasion ( P < 0. 05) ．Knockdown of IGSF10 promoted the expression of regulatory epithelial-mesenchymal transition marker Neu- ral-cadherin (N-cadherin) and key transcription factors Snail family transcriptional repressor 1 (Snail) and Snail family transcriptional repressor 2 (Slug) (P＜0. 05) and inhibited the expression of Epithelial-cadherin (E-cad- herin) (P＜0. 05) ． Conclusion Knockdown of IGSF10 may promote proliferation，migration and invasion of lung adenocarcinoma cells through activation of Snail，Slug / E-cadherin signaling axis，and this result may provide a po- tential new target for clinical diagnosis and treatment of lung adenocarcinoma.