ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 （GluR2）/Parkin signal-mediated mitophagy in rats with diabetes-related depression （DD）. MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin （STZ） tail intravenous injection + 28 days of chronic unpredictable mild stress （CUMS） combined with isolation. The rats were randomly divided into a normal group， a model group， a GluR2 blocker group （5 μg·kg^-1）， a GluR2 agonist group （10 μg·kg^-1）， a metformin + fluoxetine group （0.18 g·kg^-1 metformin + 1.8 mg·kg^-1 fluoxetine）， and high- and low-dose Zuogui Jiangtang Jieyu prescription groups （20.52 and 10.26 g·kg^-1， respectively）. The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling， respectively， while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate （ATP） in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2， Parkin， regulating synaptic membrane exocytosis protein 3 （RIMS3）， and postsynaptic density protein 95 （PSD95） in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group， the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming （P<0.01）， lowered levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.01）， increased autophagosomes of hippocampal neurons， significantly damaged morphology and structure of dendrites and spines of hippocampal neurons， decreased expression levels of GluR2， RIMS3， and PSD95 in hippocampus， and an increased Parkin expression level （P<0.05， P<0.01）. Compared with the model group， the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes， respectively （P<0.05， P<0.01）. The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically， the two groups saw elevated levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.05， P<0.01）， restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons， up-regulated protein expression levels of GluR2， RIMS3， and PSD95， and down-regulated Parkin expression level （P<0.05， P<0.01）. ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats， the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.

Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment. However, there are limitations, including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision, associated with gas therapy. In this study, we developed a series of photoactivatable nitric oxide (NO) donors NRh-R-NO (R = Me, Et, Bn, iPr, and Ph) based on an N-nitrosated upconversion luminescent rhodamine scaffold. Under the irradiation of 808 nm light, only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence (FUCL) signal at 740 nm, ascribed to lower N-N bond dissociation energy. We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy, including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation, the superoxide anion O₂^⋅- produced by the photodynamic therapy (PDT) effect of NRh-Ph, and highly toxic peroxynitrite anion (ONOO^‒) generated from the co-existence of NO and O₂^⋅-. After mild nano-modification, the nanogenerator (NRh-Ph-NO NPs) empowered with superior biocompatibility could target mitochondria. Under an 808 nm laser irradiation, NRh-Ph-NO NPs could induce NO/ROS to generate RNS, causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation, which further induced tumor immunogenic cell death (ICD). In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy, demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging. Collectively, this versatile strategy defines the targeted RNS-mediated cancer therapy.

Objective To investigate the mediating role of medical coping strategies in the relationship between perceived social support and resilience among patients with occupational pneumoconiosis (hereinafter referred to as pneumoconiosis). Methods A total of 240 pneumoconiosis patients were selected as the study subjects using the convenience sampling method. The Perceived Social Support Scale, the 10-item Connor-Davidson Resilience Scale and Medical Coping Strategies Questionnaire were used to evaluate their perceived social support, resilience and medical coping strategies. AMOS 26.0 software was used to construct the structural equation model. Results The average scores of perceived social support and resilience were (56.6±0.9) and (20.9±7.5), respectively. The scores for the dimensions of confrontation, avoidance and resignation of medical coping strategies were (20.2±3.6), (11.2±3.1) and (18.1±2.9), respectively. The score of resilience was positively correlated with the score of perceived social support, avoidance dimension and confrontation dimension of medical coping strategies (r=0.260, 0.176, 0.174, all P<0.01). It was negatively correlated with resignation coping (r=-0.292, P<0.01). The results of mediating effect test showed that the total effect of perceived social support on resilience was 0.252 [95% confidence interval (CI) was 0.056-0.448], which mainly affected the resilience by affecting the resignation coping (95%CI: -0.458 to -0.104), with the indirect effect value of 0.120, accounting for 47.6% of the total effect. Conclusion The resilience of pneumoconiosis patients is moderately low. Resignation coping in medical coping strategies plays a mediating role between perceived social support and resilience in pneumoconiosis patients.

Objective To explore the effects of Jianpi Yichang Powder on the expressions of interleukin(IL)-1β and IL-18 of NLRP3 signaling pathway in ulcerative colitis(UC)model rats.Methods Ten rats were randomly selected from 40 SD rats as the normal group,and the other rats freely drank 5%dextran sulfate solution for 7 days to replicate UC rats model.The model rats were randomly divided into model group,sulfasalazine group and Jianpi Yichang Powder group,with 10 rats in each group.Jianpi Yichang Powder group and sulfasalazine group were given corresponding liquid medicine for gavage,and the normal and model groups were given equivalent volume distilled water for gavage for consecutive 14 d.The general status was observed,and the disease activity index(DAI)was scored,the contents of NLRP3,apoptosis-associated spotted proteins(ASC),and Caspase-1 in serum were detected by ELISA,the expressions of IL-1β and IL-18 protein and mRNA in colon tissue were detected by immunohistochemistry,Western blot and RT-PCR respectively.Results Compared with the normal group,the general status of the rats in model group was relatively worse,and DAI score significantly increased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum were significantly increased(P<0.01),the expressions of IL-1β and IL-18 protein and mRNA in colon tissue were significantly increased(P<0.01).Compared with the model group,the general status of the rats in Jianpi Yichang Powder group and sulfasalazine group were significantly improved,DAI score significantly decreased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum significantly reduced(P<0.05,P<0.01),and the expressions of IL-1β and IL-18 protein and mRNA in colon tissue significantly decreased(P<0.05,P<0.01).Conclusion Jianpi Yichang Powder can inhibit IL-1β and IL-18 expression of NLRP3 signaling pathway to reduce colon immune inflammatory damage,thus play a role in treating UC.

Objective To explore the effects and mechanism of Baishile Capsules regulating SHH/Gli1 signaling pathway on hippocampal neurogenesis of depression model rats.Methods Totally 32 SD rats were randomly divided into control group,model group,fluoxetine(5.4 mg/kg)group and Baishile Capsules(2.88 g/kg)group,with 8 rats in each group.A depression rat model was established using chronic unpredictable mild stress and single cage feeding method.The model was established and administered simultaneously for 21 consecutive days.Depression-like behavior in rats were evaluated by sucrose preference experiment and open field experiment,ELISA was used to detect brain derived neurotrophic factor(BDNF)contents in rat serum and hippocampal tissue,the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus was observed by immunofluorescence,immunofluorescence and Western blot were used to detect the fluorescence intensity and protein expression of SHH,Gli1,Smo,Ptch in hippocampal tissue.Results Compared with the control group,the degree of sucrose preference significantly decreased in the model group(P<0.01),the number of horizontal and vertical movements significantly decreased(P<0.01),the contents of BDNF in serum and hippocampal tissue significantly decreased(P<0.05),the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus significantly decreased(P<0.01),and the fluorescence intensity and protein expression of SHH,Gli1,Smo,Ptch in hippocampal tissue significantly decreased(P<0.01,P<0.05).Compared with the model group,the degree of sucrose preference and the number of horizontal and vertical movements in fluoxetine group and Baishile Capsule group increased significantly(P<0.05,P<0.01),the contents of BDNF in serum and hippocampal tissue significantly increased(P<0.05,P<0.01),and the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus significantly increased(P<0.01,P<0.05),the fluorescence intensity and protein expressions of SHH,Gli1,Smo,Ptch in hippocampal tissue significantly increased(P<0.01,P<0.05).Conclusion Baishile Capsule can promote the hippocampus neurogenesis in depression model rats by regulating SHH/Gli1 signaling pathway,and play an antidepressant role.

Sishen Pills is a classic prescription for the treatment of spleen and kidney diarrhea,which has the effect of warming the kidney and the spleen,astringent intestine and antidiarrheal.In modern clinical application,the modified prescriptions based on Sishen Pills,combined with other treatments of TCM and integrated traditional Chinese and Western medicine are often used to treat ulcerative colitis with spleen-kidney yang deficiency syndrome,and the curative effect is remarkable.Experimental pharmacological studies have shown that Sishen Pills may achieve the purpose of ulcerative colitis by regulating the expression of related signaling pathway proteins,regulating inflammatory factors,inhibiting inflammatory response,regulating autophagy,regulating intestinal flora,improving intestinal mucosal permeability,repairing intestinal mucosal barrier,regulating cellular energy metabolism,anti-oxidative stress,regulating cellular immune function,etc.In this article,the research status of Sishen Pills in the treatment of ulcerative colitis was sorted out and summarized,in order to provide reference for further study of its mechanism and clinical application.

Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

Objective To observe the effects of Simo Decoction on the expressions of vasoactive intestinal peptide(VIP)and its receptor 2(VIPR2)in rats with functional dyspepsia(FD)of liver and spleen stagnation syndrome;To investigate its mechanism of action in regulating gastrointestinal motility.Methods Totally 60 SD rats were randomly divided into blank group,model group,mosapride group(0.305 mg/kg)and Simo Decoction high-,medium-and low-dosage groups(5.62,2.81,1.40 g/kg).The liver and spleen qi stagnation FD rat model was prepared by multifactorial modeling method,and the corresponding drugs were given by gavage for 14 days.The general conditions of rats in each group were observed,and body mass,gastric emptying rate and small intestine propulsion rate were measured;the histological structure of gastric antrum tissue and duodenal tissue were observed by HE staining;the positive expressions of VIP and VIPR2 in duodenal tissue were observed by immunohistochemistry;the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue were detected by Western blot and RT-PCR,respectively.Results Compared with the blank group,the general condition of the rats in model group was poorer,body mass,gastric emptying rate and small intestine propulsion rate were significantly lower(P<0.01),and the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue significantly increased(P<0.05,P<0.01).Compared with the model group,the body mass,gastric emptying rate and small intestine propulsion rate in Simo Decoction high-and medium-dosage groups and the mosapride group significantly increased(P<0.05,P<0.01),and the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue significantly decreased(P<0.05,P<0.01).HE staining showed no significant changes in the morphology of gastric antrum and duodenum tissues.Conclusion Simo Decoction may promote gastrointestinal motility by inhibiting the expressions of VIP and VIPR2 in duodenal tissue of FD rats with liver and spleen qi stagnation,thereby improving FD.

Objective To investigate the effects of Jianpi Yichang Powder on regulating the NLRP3 inflammasome signaling pathway to inhibit dendritic cells(DCs)inflammatory injury induced by TNF-α;To explore its mechanism in the treatment of ulcerative colitis.Methods C57BL/6 mice DCs were primitively isolated and cultured.The cultured DCs were randomly divided into the normal group,model group,negative control group,positive drug group and TCM group.DCs inflammatory microenvironment model was established by TNF-α induction.After corresponding treatments were given to each group,CCK-8 method was used to detect cell proliferation ability,immunofluorescence and Western blot were used to detect the protein expressions of NLRP3,ASC and Caspase-1 in DCs respectively,Western blot and RT-PCR were used to detect the protein and mRNA expressions of IL-1β and IL-18 in DCs.Results Compared with the normal group,the proliferation ability in DCs of model group significantly decreased(P<0.01),the positive expressions of NLRP3,ASC and Caspase-1 significantly increased,the expressions of NLRP3,ASC,Caspase-1,IL-18,IL-1β protein and IL-18,IL-1β mRNA in DCs significantly increased(P<0.01).Compared with the model group and negative control group,the proliferation ability of DCs significantly increased in positive drug group and TCM group(P<0.01),the positive expressions of NLRP3,ASC,and Caspase-1 significantly decreased(P<0.01),the protein expressions of NLRP3,ASC,Caspase-1,IL-1β and IL-18 significantly decreased(P<0.05,P<0.01),and the mRNA expressions of IL-1β and IL-18 significantly decreased(P<0.01).The cell proliferation ability,Caspase-1 positive expression,and IL-18 mRNA expression of TCM group were significantly higher than those of the positive drug group(P<0.05),while the mRNA expression of IL-1β was lower than that of the positive drug group(P<0.05).Conclusion Jianpi Yichang Powder can inhibit the inflammatory response of DCs induced by TNF-α,and its mechanism in the treatment of ulcerative colitis may be related to regulating the expressions of the NLRP3 inflammasome signaling pathway,including the expressions of NLRP3,ASC,Caspase-1,IL-18 and IL-1β.

Pathological mechanism of ulcerative colitis(UC)is not fully clear,which may be the result of Th17/Treg immune imbalance and the interaction of multiple complex factors.Numerous studies have found that classical TCM prescriptions,experienced formulas and TCM active components could regulate Th17/Treg balance by intervening in cytokines,transcription factors,and signaling pathways,restore intestinal mucosal immune function,suppress intestinal mucosal inflammatory response,and repair intestinal mucosal barrier damage.Based on the research status of UC,Th17/Treg balance and TCM treatment,this article reviewed the relationship between Th17/Treg balance and UC,and explained the key role of Th17/Treg balance in the occurrence and development of UC.At the same time,the Chinese materia medica targeting to regulate the balance of Th17/Treg in the treatment of UC in recent years was summarized,in order to provide reference for the treatment of UC.