Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

The incidence and mortality rates of lung cancer remain high, making it the leading cause of cancer-related deaths. In women, the predominant histological subtype is lung adenocarcinoma, commonly associated with epidermal growth factor receptor (EGFR) mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve patient prognosis. Metastasis of primary lung cancer to the endometrium is extremely rare and is often misdiagnosed as a primary reproductive system tumor, and its occurrence indicates poor prognosis. This article reports a case of an advanced lung adenocarcinoma patient with EGFR mutation, who developed abnormal vaginal bleeding after EGFR-TKIs treatment failure, and biopsy confirmed endometrial metastasis. A review of similar cases is also presented.
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Humans ; Female ; ErbB Receptors/metabolism* ; Endometrial Neoplasms/genetics* ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Adenocarcinoma of Lung/drug therapy* ; Treatment Failure ; Middle Aged ; Adenocarcinoma/genetics*

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

Objective To evaluate the efficacy and safety of ozone injection therapy for lumbar disc hemiation(LDH).Methods A computerized retrieval of academic papers concerning the randomized controlled trial(RCT)on ozone injection therapy for LDH from the databases of Embase,PubMed,Cochrane library and Web of science was conducted.The retrieval time period was from the establishment of the database to February 2023.The literature retrieval,screening,and data extraction were independently performed by two researchers.Cochrane bias risk assessment tool was used to assess the quality of the included literature.Stata 17.0 software was used to make meta-analysis.Results A total of 9 RCTs including 702 patients were finally included in this study.The results of meta-analysis showed that compared with radiofrequency thermocoagulation,percutaneous rotation and other treatments for LDH,the combination use of ozone injection could signifiicantly improve the effective rate based on Macnab efficacy evaluation criteria(RR=1.097,95％CI:1.038～1.159,P=0.001)and the excellent rate(RR=1.185～95％CI:1.074～1.309,P=0.001),and decrease the visual analog scale(VAS)pain score(WMD=-0.810～95％CI:-1.205～-0.414,P=0.000),and the differences in the above indexes were statistically significant.Conclusion Compared with the simple use of radiofrequency thermocoagulation,percutaneous rotation,and other treatment for LDH,the combination use of ozone injection therapy can significantly improve the effective rate and excellent rate based on Macnab efficacy evaluation criteria,decrease VAS score,with a high clinical safety.Limited by the quantity and quality of the original studies included in this study,the above conclusions need to be further verified by multi-center,large-sample and high-quality studies.

Objective:To explore the predictive value of multimodal ultrasound (MMU) for upper urinary tract damage (UUTD) in children with neurogenic bladder (NB).Methods:This was a case-series study.From January 2022 to December 2023, 87 children with NB admitted to the First Affiliated Hospital of Zhengzhou University were examined by MMU.During the filling of bladder, vesical volume (VV), bladder wall thickness (BWT), shear wave velocity (SWV) of the anterior wall, resistance index (RI), and vascularization index (VI) were measured.After the emptying of bladder, VV and anterior wall SWV were measured, and ultrasound bladder compliance (△C) was calculated.The anterior posterior diameter (APD) of the renal pelvis and ureteral diameter (UD) were also measured.According to the upper/lower urinary tract dysfunction classification criteria, NB children were divided into a UUTD group and a non-UUTD (NUUTD) group.The differences in clinical data and related examinations between the 2 groups were analyzed to screen out independent risk factors, and an early warning model was established based on these factors.The prediction efficiency of the model and the urodynamic study (UDS) for UUTD was compared.Results:(1) There were 47 children in the UUTD group and 40 children in the NUUTD group.There was no significant difference in gender, age and body mass index between the 2 groups (all P>0.05).(2) In the UUTD group, the total glomerular filtration rate (tGFR) was (70.45±16.17) mL/min, the incidence of hydronephrosis was 38.30%, and the incidence of ureteral dilatation was 23.40%.No morphological changes were found in the imaging examination of the urinary system in the NUUTD group, and its tGFR was (100.55±16.27) mL/min.There was a significant difference in tGFR between the 2 groups ( P<0.05).(3) The filling VV, emptying VV, mean BWT, filling SWV, emptying SWV, VI, mean RI, △C, maximum cystometric capacity (MCC), maximum detrusor pressure during filling (Pdet.max), bladder compliance (BC), and detrusor leak point pressure (DLPP) in the NUUTD group were (218.43±87.53) mL, (14.62±6.14) mL, (3.08±0.65) mm, (2.64±0.54) m/s, (1.88±0.41) m/s, (6.20±1.04)%, 0.68±0.04, (147.58±49.18) mm 2·s, (309.50±66.54) mL, (59.83±19.79) cmH 2O(1 cmH 2O=0.098 kPa), (25.80±10.34) mL/cmH 2O, and (34.00±6.16) cmH 2O, respectively.Compared with the NUUTD group, the UUTD group showed decreased filling VV [(167.21±85.63) mL], △C [(78.49±31.86) mm 2·s], VI [(5.01±0.81) %], MCC [(255.32±75.10) mL], and BC [(12.57±6.44) mL/cmH 2O], and increased emptying VV [(19.50±7.65) mL], mean BWT [(4.02±0.82) mm], filling SWV [(3.99±1.07) m/s], emptying SWV [(2.15±0.35) m/s], mean RI (0.70±0.08), Pdet.max [(75.94±26.23) cmH 2O], and DLPP [(48.13±12.61) cmH 2O] (all P<0.05).(4) The decreased BC ( OR=0.841, 95% CI: 0.562-1.256, P=0.045), △C ( OR=0.427, 95% CI: 0.202-0.904, P=0.026) and VI ( OR=0.461, 95% CI: 0.091-2.325, P=0.010) and the increased DLPP ( OR=1.139, 95% CI: 0.894-1.451, P=0.040), filling SWV ( OR=1.895, 95% CI: 1.082-3.321, P=0.007) and mean BWT ( OR=1.191, 95% CI: 0.850-1.669, P=0.025) were independent risk factors for UUTD.Among MMU parameters, filling SWV had the highest prediction efficiency for UUTD, with a threshold of 3.33 m/s, sensitivity of 72.34% and specificity of 92.50%. Conclusions:MMU can well predict the occurrence of UUTD in children with NB, and filling SWV has the highest prediction efficiency.

Objective To investigate the risk factors associated with necrosis in interstitial oedematous pancreatitis(IOP)and to develop a nomogram model for the early prediction of necrosis in IOP.Methods A retrospective analysis was conducted on 306 patients diagnosed with IOP.Patients were stratified into necrosis and edema groups based on the presence or absence of pancreatic necrosis through follow-up CT-enhanced examinations.Logistic regression analysis was employed to identify independent predictive factors for necrosis in IOP.Subsequently,a nomogram model was developed,and its discriminative ability,accuracy,and practicality were assessed through receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Balthazar computed tomography severity index(CTSI),gender,lactate dehydrogenase(LDH),and triglyceride(TG)were finally identified as four independent predictors for constructing the nomogram model.The area under the curve(AUC)of the nomogram model was 0.800[95％confidence interval(CI)0.731-0.869].The calibration curve indicated good consistency between the predicted probabil-ity and the actual probability of necrosis in IOP(P=0.737).DCA suggested high practicality of the nomogram model within the threshold probability range of 3％to 66％and 75％to 96％.Conclusion The nomogram model based on Balthazar CTSI,gender,LDH,and TG demonstrates good efficacy in early prediction of necrosis in IOP.

Objective To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1(BZW1)in gastric cancer,its impact on patient prognosis and the underlying mechanisms.Methods TIMER,UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients'prognosis.We further analyzed BZW1 expressions,disease progression,and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January,2014 and December,2016.Gastric cancer MGC803 cells were examined for changes in migration,invasion,and epithelial-mesenchymal transition(EMT)following lentivirus-mediated BZW1 overexpression or knockdown.Results The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues,respectively(P<0.01).BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels(P<0.01).A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery(P<0.05,HR=2.070,95%CI:1.021-4.196).At the cut-off value of 3.61,BZW1 expression had a sensitivity of 75.56%and a specificity of 71.93%for predicting postoperative 5-year mortality(P<0.01).In MGC803 cells,BZW1 overexpression obviously promoted cell migration and invasion(P<0.05),enhanced cellular expressions of N-cadherin and vimentin(P<0.05)and inhibited the expression of E-cadherin(P<0.05).Enrichment analysis suggested the involvement of BZW1 in the Wnt/β-catenin signaling pathway.Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a,β-catenin and C-myc in MGC803 cells(P<0.05).Conclusion BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/β-catenin signaling pathway to promote EMT of gastric cancer cells.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

Objective To investigate the mechanism underlying the neuroprotective effect of linarin(LIN)against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury(SCI).Methods Fifty C57BL/6J mice(8-10 weeks old)were randomized to receive sham operation,SCI and linarin treatment at 12.5,25,and 50 mg/kg following SCI(n=10).Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale,inclined plane test,and footprint analysis,and spinal cord tissue damage and myelination were evaluated using HE and LFB staining.Nissl staining,immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue.In cultured BV2 cells,the effects of linarin against lipopolysaccharide(LPS)-induced microglia activation,inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining,Western blotting,RT-qPCR,and ELISA.In a BV2 and HT22 cell co-culture system,Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation.Results Linarin treatment significantly improved locomotor function(P<0.05),reduced spinal cord damage area,increased spinal cord myelination,and increased the number of motor neurons in the anterior horn of the SCI mice(P<0.05).In both SCI mice and cultured BV2 cells,linarin effectively inhibited glial cell activation and suppressed the release of iNOS,COX-2,TNF-α,IL-6,and IL-1β,resulting also in reduced neuronal apoptosis in SCI mice(P<0.05).Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF-κB signaling pathway.In the cell co-culture experiments,linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells(P<0.05).Conclusion The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF-κB signaling pathway,which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.