Aim To establish the pyroptosis model of rat chondrocytes induced by tumor necrosis factor α(TNF-α)in order to study the effect of lysine acetyl-transferase 7(KAT7)on pyroptosis of chondrocytes.Methods Chondrocytes of rat knee joint were isolated by type Ⅱ collagenase digestion,and were identified by toluidine blue staining and Col Ⅱ immunofluorescence.CCK-8 was used to evaluate cell viability.Western blot was used to detect the expression of pyroptosis-related proteins NLRP3,GSDMD,caspase-8 and KAT7 in cells intervened with TNF-α,adenovirus overexpression of KAT7(KAT7-oe)and KAT7 inhibitor WM-3835.The microstructure of the cells was observed by scanning e-lectron microscopy.Pyroptosis was detected by TUNEL staining,and the expression of pyroptosis-related pro-tein and KAT7 was detected by immunofluorescence.Results Compared with the empty virus group,KAT7-oe inhibited cell viability,promoted the expression of pyroptosis-related proteins,and TNF-α enhanced this effect.At the same time,the expression of KAT7 and pyroptosis-related proteins in the TNF-α stimulation group increased,and WM-3835 reduced the related proteins expression.Electron microscopy showed that KAT7-oe caused cell swelling,deformation,membrane perforation and rupture,while WM-3835 could restore cell morphology.TUNEL staining and immunofluores-cence results also confirmed that KAT7-oe induced chondrocyte pyroptosis,and WM-3835 could down-reg-ulate the fluorescence of pyroptosis-related proteins.Conclusions The expression of KAT7 increases in rat chondrocyte pyroptosis model,and the intervention of KAT7 expression affects signal molecules related to py-roptosis pathway,suggesting that KAT7 may be related to chondrocyte pyroptosis.

Aim To investigate the role of tryptophan 2,3-dioxygenase(TDO2)in cisplatin-acute kidney in-jury(Cis-AKI)and to explore the mechanism of TDO2 in relation to apoptosis in tubular epithelial cells(TECs)to investigate the mechanism of TDO2 associ-ated with apoptosis.Methods An AKI model was es-tablished by intraperitoneal injection of cisplatin(Cis).Colorimetric assay was used to detect CRE and BUN levels,and PAS staining was employed to observe renal injury in mice.Immunohistochemistry was used to detect TDO2 protein expression and distribution and macrophage(F4/80+)infiltration;immunofluores-cence was used to detect the co-localization of TDO2 with the tubular marker LTL;TUNEL staining was used to detect apoptosis in mouse kidney;flow cytome-try was used to detect overexpression of human renal cortical proximal tubular epithelial cells(HK2)and apoptosis after administration of the TDO2 inhibitor 680C91;Western blot was used to detect TDO2 and NF-κB pathway protein levels in HK2 cells after over-expression and inhibition of TDO2.Results In the o-verall animal experiments,Cis-AKI mice showed signif-icantly higher levels of CRE and BUN and obvious tu-bular damage compared with the control group;at the same time,the renal tissues of Cis-AKI mice showed increased expression of F4/80,and the proportion of apoptotic cells in kidney cells was increased.Immuno-histochemistry and immunofluorescence showed that the expression of TDO2 increased,mainly localized in TECs.In cellular experiments,HK2 cells overexpress-ing TDO2 increased the proportion of apoptosis,and the expression of TDO2,p-IKBα,and p-p65 proteins was elevated,and p-IKBα/IκBα and p-p65/p65 were ele-vated;furthermore,the proportion of apoptosis was re-duced by the administration of 680C91,and the expres-sion of p-IκBα,and p-p65 proteins decreased,and the expression of p-IKBα/IKBα,and p-p65/p65 de-creased.Conclusions Elevated TDO2 in TECs is in-volved in the pathological mechanism of Cis-AKI,which may be related to its induction of apoptosis in TECs and activation of the NF-κB signaling pathway and consequently renal injury.

Objective To explore the occurrence and development trajectories of symptoms at different time points in patients with acute pancreatitis (AP), and to analyze the influencing factors and preventive measures of development trajectories of AP symptom clusters. Methods A convenient sampling method was used to select AP who were admitted from January 2023 to December 2023 were selected and included in the study. The symptoms at different time points were recorded. The severities of symptom clusters in AP patients were explored, and the development trajectories of main symptom clusters were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of development trajectories of symptom clusters in AP patients. Results The incidence rates of abdominal pain, dry mouth, abdominal distension and lack of energy were higher in AP patients during hospitalization. The incidence rates of lack of energy, anxiety, abdominal pain and sleep disturbance were higher on the 1^st month after discharge. The incidence rates of abdominal distension, abdominal pain, sleep disturbance and anxiety were higher on the 3^rd month after discharge. The incidence rates of anxiety, abdominal pain and irritability were higher on the 6^th month after discharge. The fatigue symptom cluster, psychological symptom cluster and gastrointestinal symptom cluster were extracted during hospitalization and on the 1^st month and the 3^rd month after discharge, and the psychological symptom cluster and gastrointestinal symptom cluster were extracted on the 6^th month. The severity scores of symptom clusters at each time point were statistically different (P<0.05). The development of gastrointestinal symptom cluster in AP patients was mainly low decline. The development of psychological symptom cluster was mainly high decline. Drinking history and diabetes mellitus were the influencing factors of development trajectory of gastrointestinal symptom cluster in AP patients (P<0.05). High disease severity, drinking history and biliary tract disease were the influencing factors of development trajectory of psychological symptom cluster in AP patients (P<0.05). Conclusion The symptom clusters of AP patients changes over time, with digestive, fatigue, and psychological symptoms being the main groups in the early stage, and psychological and digestive symptoms persisting in the later stage. Early identification and intervention are crucial for improving the prognosis of AP patients.

Nitrogen dioxide(NO 2)is a prevalent air pollutant that poses significant threats to the environment and human health,emphasizing the urgent need for high-performance NO 2 sensors for effective environmental monitoring at room temperature.Sensors based on metal halide perovskites have emerged as promising candidates for gas detection at room temperature,but their long-term stability remains a major challenge.In this study,a methylamine thiocyanate(MT)-doped FA 0.8Cs 0.2PbI 2Br(PVK)gas sensor(MT-PVK)was prepared using a simple one-step spin-coating method and ethyl acetate(EA)anti-solvent extraction technique.The crystalline structure,chemical composition,and particle morphology of the MT-PVK thin film were characterized.The MT-PVK thin film was then utilized as a gas sensor for NO 2 detection at room temperature.The results demonstrated that the sensor exhibited outstanding selectivity and reversibility at low concentrations of NO 2 gas,with a detection limit as low as 33 ppb(10-9,nL/L).For 10 ppm(10-6,μL/L)NO 2,the sensor showed rapid response and recovery time of only 1.6 s and 27 s,outperforming most traditional metal oxide NO 2 sensors.Furthermore,compared to the original PVK,the MT molecules significantly enhanced the structural and sensing stability of the MT-PVK sensor under high humidity conditions(55%±5%).These findings suggested that MT-doped FA 0.8Cs 0.2PbI 2Br perovskite gas sensors offered a promising pathway for the development of rapid-response gas sensing technologies suitable for room temperature operation.

AIM To investigate the effects of Changpu Yujin Decoction(CPYJD)on striatal mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome(TS).METHODS Thirty-six SPF male SD rats were randomly assigned to the control group(n=9)and the TS modeling group(n=27).Rats in the modeling group received daily intraperitoneal injections of 3,3'-iminodipropionitrile(IDPN)(300 mg/kg)for 7 consecutive days to establish the TS model.Post-modeling,successfully induced TS rats were re-randomized into model group(no treatment),tiapride group(47.91 mg/kg)and CPYJD group(77.28 g/kg).All groups received their respective interventions via intragastric administration daily for 28 days.Following drug administration,behavioral scores were assessed in each group.Pathological alterations in the striatum were examined using HE staining,while ultrastructural changes were evaluated by transmission electron microscopy(TEM).Neuronal apoptosis was quantified via TUNEL staining,and ROS levels in striatum were measured by ELISA.Co-localization of PINK1 and LC3B was assessed using immunofluorescence(IF).Finally,mRNA and protein expressions of PINK1,Parkin,Beclin-1,P62 and LC3B(LC3B-Ⅱ/Ⅰ ratio)were analyzed by RT-qPCR and Western blot.RESULTS Compared to the control group,the model group demonstrated significantly increased behavioral scores(P＜0.01),elevated neuronal apoptosis rate and higher ROS levels in the striatum(P＜0.01);severe neuronal and mitochondrial damage in the striatum;significantly reduced mRNA and protein expressions of PINK1,Parkin,Beclin-1 and LC3B(LC3B-Ⅱ/Ⅰ ratio)in the striatum(P＜0.01);markedly upregulated P62 mRNA and protein expressions(P＜0.01).Compared to the model group,both the tiapride and CPYJD intervention groups exhibited significantly reduced behavioral scores(P＜0.01);decreased neuronal apoptosis rate and lower ROS levels(P＜0.01);improved pathological alterations in the striatal neurons and mitochondria;increased mRNA and protein expressions of PINK1,Parkin and Beclin-1 in the striatum(P＜0.05,P＜0.01);and decreased P62 mRNA and protein expressions(P＜0.01).Furthermore,the rats in the CPYJD group specifically showed elevated LC3B mRNA level and LC3B-Ⅱ/Ⅰ protein ratio in striatum(P＜0.05,P＜0.01).CONCLUSION The effect of CPYJD intervention in TS rats may involve activation of mitophagy through regulation of the PINK1/Parkin signaling pathway,improving mitochondrial function,reducing ROS levels,and thereby protecting neurons.

Aim To investigate the effect of PU.1 in-hibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism.Methods Thirty female MRL/lpr mice were randomly divided into the model group,DB2313 group and TACI-Ig group,with 10 mice in each group.Another 10 female BALB/c mice were se-lected as normal control groups.Mice in the DB2313 group received intraperitoneal DB2313 injections every two days,and those in the TACI-Ig group received subcutaneous injections of TACI-Ig every two days.Mice in the control group and model group were intra-gastrically given the same amount of 0.9％NaCl injec-tion every day.Before the drug intervention and for 1 to 5 weeks after the intervention,the urine of mice was collected regularly,the urine protein content was meas-ured,and the renal damage index was evaluated.The histopathological changes of kidney were observed by HE,Masson and PAS staining.The expression levels of immune complex of C3 in kidney tissue were detec-ted by immunohistochemistry.The concentrations of u-rea nitrogen(BUN),serum creatinine(Scr),inter-leukin-6(IL-6),and tumor necrosis factor alpha(TNF-α)in the serum samples were assayed utilizing the respective kits.The expression levels of PU.1 and FLT3 in kidney tissues were determined by immunoflu-orescence technology,and the protein expressions of PU.1,FLT3,PI3K,AKT and phosphorylated AKT(p-AKT)in kidney tissues were detected by Western blot.Results DB2313 treatment significantly allevia-ted the pathological damage of kidney in MRL/lpr mice,and reduced the deposition of C3,kidney injury index and 24-hour urine protein in renal tissue.The results of ELISA showed that DB2313 administration could significantly reduce the serum levels of BUN,Scr,IL-6 and TNF-α in MRL/lpr mice.The results of immunofluorescence and Western blot further showed that DB2313 treatment could significantly down-regu-late the protein expression of PU.1,PI3K and p-AKT,and up-regulate the protein expression of FLT3.Con-clusion DB2313 has an ameliorating effect on lupus nephritis in MRL/lpr mice,and its underlying mecha-nism may involve the inhibition of the transcription fac-tor PU.1-mediated signaling pathway.

Aim To investigate the role and mecha-nism of allopurinol(ALLO)in restoring the abnormal metabolism of kynurenine(Kyn)mediated by trypto-phan-2,3-dioxygenase 2(TDO2)to ameliorate ulcera-tive colitis(UC)in mice,and to provide experimental basis for the treatment of UC by ALLO.Methods A dextran sodium sulfate(DSS)-induced mouse UC mod-el was established,and the mice were randomly divided into the control group,the model group,the ALLO low,medium and high-dose groups(10,20,and 40 mg·kg-1),and the positive-significant salazosulfapyridine(SASP)(200 mg·kg-1)group.The body mass and disease activity index(DAI)scores of mice were re-corded;HE staining was performed to observe the de-gree of pathological damage in colon tissue;Western blot was performed to detect TDO2 protein expression in colon tissue;flow cytometry was performed to detect changes in the proportion of macrophages in spleen and mesenteric lymph nodes;ELISA was employed to de-tect the levels of TNF-α,IL-1β and IL-6 pro-inflamma-tory cytokines in the supernatant of colon tissue homog-enate;high performance liquid chromatography(HPLC)was used to detect the levels of tryptophan(Trp)and Kyn in the supernatant of colon tissue ho-mogenate.Results Compared with the model group,ALLO administration significantly ameliorated colonic histopathological injury in UC mice,decreased the pro-portion of macrophages in spleen and mesenteric lymph nodes,down-regulated the levels of TNF-α,IL-1 β,and IL-6 pro-inflammatory factors in serum of homogenate of colonic tissues,and inhibited the activity(Kyn/Trp ratio)and expression of TDO2 in colonic tissues.Con-clusion ALLO improves disease manifestations in mice with ulcerative colitis,which may be related to its restoration of abnormal Kyn metabolism.

Aim To investigate the effect of PU.1 in-hibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism.Methods Thirty female MRL/lpr mice were randomly divided into the model group,DB2313 group and TACI-Ig group,with 10 mice in each group.Another 10 female BALB/c mice were se-lected as normal control groups.Mice in the DB2313 group received intraperitoneal DB2313 injections every two days,and those in the TACI-Ig group received subcutaneous injections of TACI-Ig every two days.Mice in the control group and model group were intra-gastrically given the same amount of 0.9％NaCl injec-tion every day.Before the drug intervention and for 1 to 5 weeks after the intervention,the urine of mice was collected regularly,the urine protein content was meas-ured,and the renal damage index was evaluated.The histopathological changes of kidney were observed by HE,Masson and PAS staining.The expression levels of immune complex of C3 in kidney tissue were detec-ted by immunohistochemistry.The concentrations of u-rea nitrogen(BUN),serum creatinine(Scr),inter-leukin-6(IL-6),and tumor necrosis factor alpha(TNF-α)in the serum samples were assayed utilizing the respective kits.The expression levels of PU.1 and FLT3 in kidney tissues were determined by immunoflu-orescence technology,and the protein expressions of PU.1,FLT3,PI3K,AKT and phosphorylated AKT(p-AKT)in kidney tissues were detected by Western blot.Results DB2313 treatment significantly allevia-ted the pathological damage of kidney in MRL/lpr mice,and reduced the deposition of C3,kidney injury index and 24-hour urine protein in renal tissue.The results of ELISA showed that DB2313 administration could significantly reduce the serum levels of BUN,Scr,IL-6 and TNF-α in MRL/lpr mice.The results of immunofluorescence and Western blot further showed that DB2313 treatment could significantly down-regu-late the protein expression of PU.1,PI3K and p-AKT,and up-regulate the protein expression of FLT3.Con-clusion DB2313 has an ameliorating effect on lupus nephritis in MRL/lpr mice,and its underlying mecha-nism may involve the inhibition of the transcription fac-tor PU.1-mediated signaling pathway.

Aim To investigate the role and mecha-nism of allopurinol(ALLO)in restoring the abnormal metabolism of kynurenine(Kyn)mediated by trypto-phan-2,3-dioxygenase 2(TDO2)to ameliorate ulcera-tive colitis(UC)in mice,and to provide experimental basis for the treatment of UC by ALLO.Methods A dextran sodium sulfate(DSS)-induced mouse UC mod-el was established,and the mice were randomly divided into the control group,the model group,the ALLO low,medium and high-dose groups(10,20,and 40 mg·kg-1),and the positive-significant salazosulfapyridine(SASP)(200 mg·kg-1)group.The body mass and disease activity index(DAI)scores of mice were re-corded;HE staining was performed to observe the de-gree of pathological damage in colon tissue;Western blot was performed to detect TDO2 protein expression in colon tissue;flow cytometry was performed to detect changes in the proportion of macrophages in spleen and mesenteric lymph nodes;ELISA was employed to de-tect the levels of TNF-α,IL-1β and IL-6 pro-inflamma-tory cytokines in the supernatant of colon tissue homog-enate;high performance liquid chromatography(HPLC)was used to detect the levels of tryptophan(Trp)and Kyn in the supernatant of colon tissue ho-mogenate.Results Compared with the model group,ALLO administration significantly ameliorated colonic histopathological injury in UC mice,decreased the pro-portion of macrophages in spleen and mesenteric lymph nodes,down-regulated the levels of TNF-α,IL-1 β,and IL-6 pro-inflammatory factors in serum of homogenate of colonic tissues,and inhibited the activity(Kyn/Trp ratio)and expression of TDO2 in colonic tissues.Con-clusion ALLO improves disease manifestations in mice with ulcerative colitis,which may be related to its restoration of abnormal Kyn metabolism.

AIM To investigate the effects of Changpu Yujin Decoction(CPYJD)on striatal mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome(TS).METHODS Thirty-six SPF male SD rats were randomly assigned to the control group(n=9)and the TS modeling group(n=27).Rats in the modeling group received daily intraperitoneal injections of 3,3'-iminodipropionitrile(IDPN)(300 mg/kg)for 7 consecutive days to establish the TS model.Post-modeling,successfully induced TS rats were re-randomized into model group(no treatment),tiapride group(47.91 mg/kg)and CPYJD group(77.28 g/kg).All groups received their respective interventions via intragastric administration daily for 28 days.Following drug administration,behavioral scores were assessed in each group.Pathological alterations in the striatum were examined using HE staining,while ultrastructural changes were evaluated by transmission electron microscopy(TEM).Neuronal apoptosis was quantified via TUNEL staining,and ROS levels in striatum were measured by ELISA.Co-localization of PINK1 and LC3B was assessed using immunofluorescence(IF).Finally,mRNA and protein expressions of PINK1,Parkin,Beclin-1,P62 and LC3B(LC3B-Ⅱ/Ⅰ ratio)were analyzed by RT-qPCR and Western blot.RESULTS Compared to the control group,the model group demonstrated significantly increased behavioral scores(P＜0.01),elevated neuronal apoptosis rate and higher ROS levels in the striatum(P＜0.01);severe neuronal and mitochondrial damage in the striatum;significantly reduced mRNA and protein expressions of PINK1,Parkin,Beclin-1 and LC3B(LC3B-Ⅱ/Ⅰ ratio)in the striatum(P＜0.01);markedly upregulated P62 mRNA and protein expressions(P＜0.01).Compared to the model group,both the tiapride and CPYJD intervention groups exhibited significantly reduced behavioral scores(P＜0.01);decreased neuronal apoptosis rate and lower ROS levels(P＜0.01);improved pathological alterations in the striatal neurons and mitochondria;increased mRNA and protein expressions of PINK1,Parkin and Beclin-1 in the striatum(P＜0.05,P＜0.01);and decreased P62 mRNA and protein expressions(P＜0.01).Furthermore,the rats in the CPYJD group specifically showed elevated LC3B mRNA level and LC3B-Ⅱ/Ⅰ protein ratio in striatum(P＜0.05,P＜0.01).CONCLUSION The effect of CPYJD intervention in TS rats may involve activation of mitophagy through regulation of the PINK1/Parkin signaling pathway,improving mitochondrial function,reducing ROS levels,and thereby protecting neurons.