This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC) and explore the potential molecular mechanism of Weifuchun Capsules(WFC) in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group. The normal feeding group received a regular diet, while the modeling group was subjected to the disease-syndrome combined modeling of PLGC. Specifically, the rats had free access to the water containing 120 μg·mL~(-1) N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding). After 15 weeks, the rats in the normal feeding group were randomized into control, control-NF-κB activator betulinic acid(C-BA), and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC) groups. Meanwhile, the rats in the modeling group continuously underwent the modeling procedure and were randomized into model, WFC, model-NF-κB activator(M-BA), and model-NF-κB inhibitor(M-PDTC) groups. The model group and control group were given aseptic water by intragastric administration, once a day. WFC was given at a dose(432 mg·kg~(-1)) 6 times the equivalent dose for adults(body weight: 60 kg) by gavage, once a day. The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg~(-1), twice a week. The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg~(-1), twice a week. The interventions were carried out for 4 weeks. Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE) and alcian blue-periodic acid Sthiff(AB-PAS) staining. The levels of inflammatory cytokines including interleukin(IL)-1β, IL-6, IL-18, tumor necrosis factor-alpha(TNF-α), and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of proteins associated with the NF-κB/NLRP3 inflammasome in the gastric mucosa were determined by Western blot. The positive expression areas of proteins related to NF-κB/NLRP3 inflammasome in the gastric mucosa were measured by immunohistochemistry. The results showed that compared with the control group, the model, C-BA, and M-BA groups showed significantly risen scores of mucosal inflammation, degree of inflammatory activity, gland atrophy, and intestinal metaplasia, and the model and M-BA groups showed significanly risen scores of dysplasia. Compared with the model group, the WFC group demonstrated significantly declined scores of mucosal inflammation and degree of inflammatory activity, as well as declined scores of intestinal metaplasia and dysplasia. Compared with the control group, the model and C-BA groups showed significantly elevated levels of IL-1β, IL-6, IL-18, and TNF-α in the gastric tissue, and the model group showed significantly elevated level of IL-10. In addition, the model and C-BA groups showed significantly up-regulated expression of NF-κB p65, NLRP3, cysteine-aspartic acid protease 1(caspase-1), and apoptosis-associated speck-like protein containing a CARD(ASC) in the gastric mucosa and increased positive expression areas of NF-κB p65, NLRP3, and ASC. Compared with the model group, the WFC group showed significantly decreased levels of IL-1β, IL-6, IL-18, TNF-α, and IL-10 in the gastric tissue, and the M-PDTC group showed significantly lowered levels of IL-1β, IL-18, and TNF-α in the gastric mucosa. Both WFC and M-PDTC groups demonstrated significantly down-regulated expression levels of NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), NLRP3, and caspase-1 in the gastric mucosa, along with significant decreases in the positive expression areas of NF-κB p65, NLRP3, and ASC. In conclusion, the pathogenesis of PLGC is closely related to the activation of the NF-κB/NLRP3 inflammasome signaling pathway. WFC can alleviate mucosal inflammation, inhibit glandular atrophy, partially reverse intestinal metaplasia, and reduce dysplasia to delay the process of inflammation-cancer transformation, and meanwhile it can effectively lower the levels of inflammatory cytokines and down-regulate the expression of pathway-related proteins in the stomach. Therefore, WFC may treat PLGC by inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.
Animals ; Male ; NF-kappa B/genetics* ; Rats ; Rats, Wistar ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Stomach Neoplasms/pathology* ; Inflammasomes/genetics* ; Humans ; Precancerous Conditions/metabolism* ; Capsules

OBJECTIVE: To explore the expression regulation of lipid metabolism gene ABHD5 in testes. METHODS: Differential gene analysis was performed by integrating databases of TCGA and GTEx to identify the target gene ABHD5. The expression trends of ABHD5 gene in testicular carcinoma tissue were analyzed. Human testis single-cell atlases were obtained from the Human Protein Atlas and Male Health Atlas databases to determine the expression distribution of ABHD5 across different testicular cell types. Additionally, the GTEx database was utilized to visualize the expression pattern of ABHD5 in the testis, thereby enhancing the understanding of its transcriptional profile. The relationship between ABHD5 expression and age was assessed through integrated database analysis. Western blotting and immunofluorescence were performed to detect differential expressions of ABHD5 in testicular tissues of young and aged mice respectively. RESULTS: The TCGA database indicated that the expression of ABHD5 in human testicular carcinoma tissue was significantly lower than that in normal testicular tissue which showed a negative correlation with patient survival. ABHD5 was highly expressed in germ cells of the testis reveaked from Human Protein Atlas and Male Health Atlas databases. The stability of ABHD5 protein was crucial for testicular tissue, and its expression decreased with age. Furthermore, Western blot and immunofluorescence staining demonstrated that ABHD5 expression in the testicular tissue of aged mice was significantly lower than that in young mice. CONCLUSION ABHD5 plays an important role in testicular tissue, and may be inseparable from testicular tumors and reproductive aging. However, its mechanism of action remains to be further studied.
Male ; Animals ; Mice ; Testis/metabolism* ; Humans ; Lipid Metabolism/genetics* ; 1-Acylglycerol-3-Phosphate O-Acyltransferase/metabolism* ; Testicular Neoplasms/metabolism*

Objective:To explore the clinical application of Hisense Computer-Assisted Sur-gery System(CAS)in the perioperative period of hepatectomy for liver cancer.Methods:Clinical data of patients undergoing laparoscopic hepatectomy(LH)for liver cancer from January 2021 to December 2022 were collected.Patients were divided into three groups based on surgical difficulty(low,medium,high)and further stratified into CAS-assisted subgroup and control subgroup ac-cording to whether the CAS system was used.Demographic and perioperative data were com-pared among different groups.Results:A total of 317 patients'clinical data were collected,in-cluding 31 cases in the low difficulty group,132 cases in th medium difficulty group,and 154 cases in the high difficulty group,with 108 cases(34.1％)in the CAS-assisted subgroup and 209 cases(65.9％)in the control group.In the medium difficulty group,the CAS-assisted subgroup had shorter operation time,drainage tube duration,and postoperative hospital stay compared to the control group(P＜0.001),and the AFP levels at 1 month postoperatively in the CAS-assisted sub-group were lower than those in the control group(P＜0.001).In the high difficulty group,the CAS-assisted subgroup showed shorter operation time,drainage tube duration,and postoperative hospi-tal stay,less intraoperative blood loss,and lower AFP levels 1 month post-operation compared to the control group(P＜0.001 for all).Conclusion:Preoperative CAS in medium and high difficulty laparoscopic liver resections improves perioperative outcomes.Hisense CAS effectively assists general surgeons in accurately identifying the anatomical site of liver tumors,providing precise pre-operative simulation and intraoperative navigation,thereby optimizing surgical strategies for pa-tients.

Objective:To investigate the effect of sertraline hydrochloride combined with compound chamomile lidocaine gel in the treatment of premature ejaculation(PE).Methods:We selected 80 cases of PE treated in our hospital from June 2021 to May 2023 and equally randomized them into a control and an observation group,the former medicated with compound chamomile lidocaine gel while the latter with sertraline hydrochloride in addition,both for 6 weeks.We recorded and compared the intravaginal ejaculation latency time(IELT),the number of successful sexual intercourses per week,the Premature Ejaculation Diagnostic Tool(PEDT)scores,and the incidence of adverse reactions between the two groups of patients.Results:After the treatment,the IELT was signif-icantly longer([5.39±1.17]vs[2.49±0.73]min,P＜0.05),the weekly number of successful sexual intercourses remarkably higher(1.82±0.45 vs 0.93±0.19,P＜0.05)and the PEDT scores markedly lower(7.42±2.04 vs 9.85±2.36,P＜0.05)in the observation than in the control group,but no statistically significant differences were observed in the baseline PEDT scores or the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Sertraline hydrochloride combined with com-pound chamomile lidocaine gel is definitely effective in the treatment of PE,which can significantly improve the patients'quality of sexual life,with a high safety and low incidence of adverse reactions.

As a major global public health problem, pulmonary diseases threaten human life and health while causing a huge economic burden. The messenger RNA (mRNA)-based inhalation preparation, which effectively targets pulmonary cells can overcome the problems of traditional therapy, such as high side effects, low pulmonary bioavailability, and difficulty in synthesizing target proteins in vitro, thus providing new ideas for the treatment of pulmonary diseases. However, as the lung structure is complex and mRNA has trouble entering cells, researchers have been attempting to develop a suitable nano delivery system for higher delivery efficiency. This review introduces the barriers to pulmonary delivery, discusses the recent research development of the mRNA pulmonary delivery systems, including lipid nanoparticles, polymeric nanoparticles, polypeptides and exosomes, summarizes their limitations and looks forward to the application of mRNA inhalation preparations.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective:To explore the effect of different concentrations of Chinese herbal formula,Er-miao-san(EMS)immune regulatory gene on Gnαq expression in rats with collagen-induced arthritis(CIA).Methods:In the study,we established a CIA model,and randomly divided into model groups,EMS group with 1.5,3.0 and 4.5 g/kg(L-EMS,M-EMS,H-EMS)were adminis-tered to CIA rats by gavage,methotrexate was used as a positive control group(MTX).The rats in each group were given correspond-ing drugs for treatment,and the normal control group and model group were given the same amount of normal saline gavage.ELISA detects the expression of IL-1β,IL-6 and TNF-α in rats'serum.The mRNA and protein expression of Gnαq were analyzed using qRT-PCR and Western blot.The localization of Gnαq was performed by IHC.Results:The joint of rats in CIA group showed obvious damage,tissue hyperplasia and inflammatory infiltration;the joint tissue destruction and proliferation of MTX and EMS groups were reduced;the expressions of IL-1β,IL-6 and TNF-α in CIA group were extremely increased(P<0.01).The expressions of IL-1β(except H-EMS group),IL-6 and TNF-α in MTX and EMS groups were significantly lower than those in CIA group(P<0.05).The expressions of IL-1β,IL-6 and TNF-α in L-EMS group were lower than those in the M-EMS and H-EMS groups(P<0.05,P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of CIA group were higher than those of Control group(P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of EMS and MTX groups were lower than those of CIA group(P<0.05).The expression of Gnαq mRNA and protein in the dose of 1.5 g/kg of EMS group was lower than those of the other groups(P<0.01,P<0.05).Different degree of posi-tive signal was detected in spleen and joints in different groups.Conclusion:Gnαq is expressed in spleen and joints of CIA rats,may participate in the formation of inflammatory response in CIA rats,and then mediate the formation and development of RA by down-reg-ulating the expression of Gnαq.

Colitis-associated cancer(CAC)is a specific type of colorectal cancer that develops from inflammatory bowel disease(IBD).Myeloid-derived suppressor cells(MDSCs)are a group of myeloid cells with immunosuppressive properties,and MDSCs in the tumor microenvironment proliferate and activate during the development of colitis-associated cancer,inhibiting T-cell production and impairing their function,which impedes the immunotherapeutic effect of colitis-associated cancer.In this paper,we review the immunosuppressive mechanisms of MDSCs in the development of inflammatory bowel disease to colitis-associated cancers and the current drugs targeting MDSCs for immunotherapy of inflammatory colorectal cancers,with a view to providing new strategies for the treatment of colitis-associated cancers.

Objective To investigate the effects of cinbufagin(CB)on the proliferation,migration and invasion ability as well as epithelial-mesenchymal transition(EMT)of human colon cells HCT116.Methods Logarithmically grown HCT116 cells were randomly divided into blank group and experimental-L,-M,-H groups;the blank group did not receive any treatment(0 nmol·L-1),and experimental-L,-M,-H groups were cultured in 1 640 medium containing 17.5,35 and 70 nmol·L-1 cinbufagin for 48 h.Cell counting kit-8(CCK-8)was used to detect the effect of cinbufagin on the survival rate of HCT116 cells;cloning assay was used to detect the effect of cinbufagin on the proliferation of HCT116 cells;cell scratch assay and Transwell assay were used to detect the effect of cinbufagin on the migration and invasive ability of HCT116 cells;Western blot was used to detect the expression levels of janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)pathway and EMT-related proteins of HCT116 cells.Results The number of clone formation in blank group and experimental-L,-M,-H groups were 122.67±24.42,73.67±15.82,44.33±4.51 and 21.67±1.53;the rates of migration of scratches were(44.64±9.15)％,(26.91±2.94)％,(19.28±1.52)％and(6.33±2.30)％;the number of invaded cells were 120.33±1.15,58.33±9.07,33.33±1.53 and 18.33±3.21;the relative protein expression of phosphorylated JAK-2(p-JAK-2)/JAK-2 were 1.02±0.06,0.94±0.05,0.75±0.22 and 0.49±0.22;relative protein expression of phosphorylated STAT3(p-STAT3)/STAT3 were 0.89±0.10,0.72±0.04,0.65±0.06 and 0.52±0.18;relative protein expression of E-cadherin were 0.30±0.14,0.41±0.13,0.49±0.14 and 0.69±0.17;relative protein expression of N-cadherin were 0.96±0.11,0.78±0.04,0.69±0.12 and 0.40±0.15;Snail relative protein expression were 0.89±0.08,0.62±0.15,0.44±0.15 and 0.27±0.09;Vimentin relative protein expression were 0.92±0.09,0.76±0.13,0.63±0.01 and 0.43±0.09,respectively.The above indexes in experimental-H group showed statistically significant differences compared to blank group(all P＜0.05).Conclusion HCT116 can inhibit the invasion and metastasis of human colorectal cancer cells HCT116 by inhibiting epithelial-mesenchymal transition through JAK2/STAT3 pathway.

Objective To explore the mechanism of inhibition of colorectal cancer cells HT29 proliferation,migration and invasion by bufalin through Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods Human colorectal cancer HT29 cells were randomly divided into control group and experimental-L,-M,-H groups.The cells in the control group were not treated,and the cells in the experimental-L,-M,-H groups were treated with 2.5,5.0 and 10.0 μmol·L-1 bufalin for 48 h.After HT29 cells were infected with FLAG STAT3 lentivirus,the cells were divided into lentivirus infection group and experiment-H(10.0 pmol·L-1 bufalin)+lentivirus infection group.Cell viability was detected by cell counting kit 8(CCK-8).Cloning experiment to verify cell proliferation rate;Transwell experiment verified the migration ability of cells after bufalin treatment;the transfection efficiency of lentivirus and the expression of cell-related proteins were detected by Western blot.Results After 48 h of drug action,the number of cells in the control group,experimental-L,-M,-H groups were 1 003.25±255.53,698.00±152.25,562.13±31.56 and 449.50±82.40,respectively;the number of invasive cells were 932.00±188.84,742.22±108.64,514.67±124.82 and 343.56±86.42,respectively;the protein expression level of p-JAK2 were 1.37±0.27,0.97±0.06,0.74±0.06 and 0.39±0.12,respectively.The number of cells in the control group,experimental-H group,lentivirus infection group,and experimental-H+lentivirus infection group were 906.88±211.71,389.00±143.08,1 279.38±210.34 and 604.75±12.52,respectively;the number of invasive cells were 671.22±44.74,246.11±28.16,1 080.78±119.13 and 574.78±16.23,respectively.Compared with the control group,there were statistically significant differences in the number of cell proliferation,the number of cell invasion and the relative levels of p-JAK2 in the experimental-M and-H groups(all P＜0.05).Compared with the control group,the number of cell proliferation and the number of cell invasion in the experimental-H group,the lentivirus infection group,and the high-dose experimental+lentivirus infection group were statistically significant(all P＜0.05).Conclusion Bufalin can inhibit the proliferation,migration and invasion of colorectal cancer by activating the JAK2/STAT3 signalling pathway.