Objective:To investigate effect of Gehua Jiecheng Decoction on IL-6/JAK2/STAT3 signaling pathway in colon tissue of ulcerative colitis with"inflammatory to cancer transformation"(UC-UCAC)mice of spleen deficiency and damp-heat type.Methods:Ten from 80 SPF C57BL/6 male mice were randomly selected as blank group and other 70 mice were selected as model group.After establishment of spleen deficient damp-heat model,mice were randomly divided into model group(1st,2nd and 3rd cycle),Gehua Jiecheng Decoction high,medium and low doses groups and mesalazine group,with 10 pieces per group.UC-UCAC transformation model was further established with azo methane oxide solution(AOM)/sodium glucan sulfate(DSS).Each group was treated with corresponding drugs for 4 weeks.General state of mice was observed.Score of disease activity index(DAI)was calculated.HE staining was used to observe colonic mucosa pathology of mice.EGFR,IL-6,JAK2,STAT3 and p-STAT3 proteins and genes expressions in mice colon tissues were detected by Western blot,IHC and RT-qPCR,respectively.Results:Compared with blank group,mice in model group(3rd cycle)were generally in a worse state,colon mucosal tissue was cancerous,DAI score,target proteins and genes expressions were significantly increased(P<0.01).Compared with model group(3rd cycle),general state of mice in all treatment groups were restored and colonic tissues pathology were improved to some extent.Target proteins and genes expressions in other treatment groups were significantly decreased except for Gehua Jiecheng Decoction low-dose group(P<0.01).Conclusion:Gehua Jiecheng Decoction may destroy tumor inflammatory microenvironment,repair damaged colonic mucosa tissue,delay inflamma-tion-cancer transformation process and prevent UCAC by inhibiting activation of IL-6/JAK2/STAT3 signaling pathway.

Objective:To investigate the efficacy and safety of kidney sparing treatment based on Thulium laser ablation and systematic therapy in localized high-risk upper urinary tract urothelial carcinoma (UTUC).Methods:The data of 10 patients with UTUC who received combined treatment based on Thulium laser and systematic treatment from January 2020 to December 2021 in West China Hospital were retrospectively analysed. There were 5 males and 5 females with a median age of 76 (range 52 to 87)years old. Three cases were renal pelvis tumor and 7 cases were ureter tumor including 5 cases in lower ureter and 2 cases in upper and middle ureter. Five cases were with positive urine cytology and 6 cases were with hydronephrosis. One case was muscular invasion UTUC confirmed by biopsy(cT 2+), 7 cases were high-grade invasive urothelial carcinoma (cT 1+), and 2 cases were high-grade papillary urothelial carcinoma (cT a). Among 10 cases, 5 patients refused radical nephroureterectomy(RUN), among whom 3 patients were too old or in poor general condition to tolerate RNU. One case had a solitary kidney and 1 case had bilateral tumours. Patients were treated with Thulium laser tumor ablation under ureteroscopy combined with systemic therapy. The perioperative systemic treatment included platinum-based chemotherapy±immunotherapy, RC48+ immunotherapy, and immunotherapy alone. The postoperative treatment was immunotherapy maintenance±local radiotherapy. Strict follow-up was conducted after the completion of treatment. Results:Nine patients received systemic therapy before ablation. Four cycles of platinum-based chemotherapy (cisplatin in 2 cases, carboplatin in 1 case) were used in 3 cases, and platinum-based chemotherapy + immunotherapy (6 cycles of cisplatin + toripalimab in 1 case, 4 cycles of cisplatin + toripalimab in 1 case, 4 cycles of carboplatin+ trelizumab in 1 case) was used in 3 cases, four cycle of RC48 + immunotherapy (toripalimab or trelizumab) were used in 2 cases, and four cycles of immunotherapy (toripalimab) were used in 1 case. The operations of 10 cases were successfully completed without serious complications during the perioperative period and the laser working time (42.4 ± 15.2) min. Of the 10 cases, 4 achieved complete ablation at the first ablation, and 6 patients had incomplete ablation. Among them, 2 patients achieved clinical complete remission after 1-2 cycles of systemic therapy, and 4 patients achieved complete ablation after Thulium laser ablation again.All the 10 patients were treated with immunotherapy for 1 year, and 2 of them received additional adjuvant radiotherapy. The patients were followed-up for median 40 months(range 26 to 53 months). Recurrence occurred in 5 cases, of which 3 cases underwent salvage nephroureterectomy and 2 cases underwent Thulium laser ablation under ureteroscopy again. Five patients had no tumor recurrence. None of the 10 patients had distant metastasis. At the last follow-up, 1 patient died of complications and 6 patients kept the affected kidney alive. Perioperative complications including macroscopic hematuria (8 cases), fever (3 cases), the long-term complications of ureter stenosis (4 cases).Conclusions:For localized high-risk UTUC, local Thulium laser ablation combined with systemic therapy can achieve good tumor control while preserving the affected kidney in selected patients, and its potential application value should be further evaluated.

ObjectiveTo explore the establishment and evaluation methods of the rat model of acute myocardial infarction （AMI） in coronary heart disease with the syndrome of Qi and Yin deficiency by sleep deprivation （SD） combined with isoproterenol （ISO） and preliminarily explore its biological basis. MethodForty SD rats were assigned into normal （no treatment）， SD （treatment in modified multi-platform water environment for 96 h）， ISO （subcutaneous injection of ISO at 100 mg·kg^-1 once every other day for a total of 2 times）， and SD+ISO （injection of 100 mg·kg^-1 ISO after SD for 72 h and 96 h） groups. The cardiac function was detected by small animal echocardiography. The serum levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， and cardiac troponin T （cTnT） were measured by biochemical methods. The pathological changes of the myocardial tissue were observed by hematoxylin-eosin staining. The general state， body weight， grip strength， body temperature， behaviors in open field test， serum levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， cAMP/cGMP ratio， red （R）， green （G）， blue （B） values of the tongue surface， and pulse amplitude were observed and measured to evaluate the modeling results. Enzyme-linked immunosorbent assay was employed to determine the serum levels of interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， corticotropin-releasing factor （CRF）， adrenocorticotropic hormone （ACTH）， triiodothyronine （T3）， tetraiodothyronine （T4）， cluster of differentiation 4 （CD4）， and cluster of differentiation 8 （CD8）. ResultIn terms of disease indicators， the ISO and SD+ISO groups had lower cardiac function indicators than the normal group （P<0.01）. The levels of CK， CM-MB， LDH and cTnT elevated in each model group compared with the normal group （P<0.01）. The pathological changes of myocardial tissue were obvious in the ISO and SD+ISO groups. In terms of syndrome indicators， compared with the normal group， the SD and SD+ISO groups showed decreased body weight at each time point （P<0.01）， and the ISO group showed decreased body weight at the time points of 48 h and 72 h （P<0.05， P<0.01）. The paw temperature and rectal temperature increased in the SD group （P<0.01）. The model groups showed weakened grasp strength， lowered R， G， and B values of the tongue surface （P<0.01）， prolonged immobility time （P<0.01）， reduced total distance and number of entering the central area （P<0.01）， decreased average speed （P<0.05， P<0.01）， and increased cAMP and cGMP （P<0.05， P<0.01）. The cAMP/cGMP ratio was increased in the SD+ISO group （P<0.01）， and the pulse amplitude was decreased in the SD and SD+ISO groups （P<0.01）. In terms of serological indicators，compared with the normal group， the levels of IL-18， TNF-α， SOD and MDA were significantly increased in the ISO and SD+ISO groups （P<0.01）， the CRF， ACTH， CORT， T3， T4， CD4 and CD8 in the model groups were increased （P<0.05， P<0.01）. ConclusionSleep deprivation for 96 h combined with high-dose ISO can successfully establish a rat model of acute myocardial infarction in coronary heart disease with the syndrome of Qi and Yin deficiency. The model evaluation system can be built with disease indicators of western medicine， histopathological indicators， macroscopic indicators of traditional Chinese medicine， and serological indicators.

Purpose To investigate the expression of FUT8-AS1 gene in epithelial ovarian cancer(EOC)tissues and cell lines and its relationship with clinical pathology and progno-sis,to investigate the effect of FUT8-AS on proliferation,inva-sion and EMT of epithelial ovarian cancer cell line and its possi-ble mechanism.Methods Based on GEPIA2 and Kaplan-Meier Plotter database,the expression of FUT8-AS1 in epithelial ovarian cancer and its effect on survival of patients with ovarian cancer were analyzed,the expression levels of FUT8-AS1 miR-142-5p,BCL2,and EMT marker genes were detected by qRT-PCR,CCK-8 and Transwell assays were used to detect the effect of abnormal expression of FUT8-AS1 gene on proliferation and invasion of CAOV3 cells.The interaction between FUT8-AS1 and miR-142-5p was verified by Dual-luciferase reporter assay sys-tem.Results Using GEPIA2 and Kaplan-Meier Plotter data-bases,it was found that the expression of FUT8-AS1 in epitheli-al ovarian cancer tumor tissue was significantly higher than that in normal tissue(P＜0.05),and the overall survival rate of the high expression group of FUT8-AS1 was significantly lower than that of the low expression group of FUT8-AS1(P＜0.01).The expression of FUT8-AS1 gene in 74 cases of epithelial ovarian cancer tissue was significantly higher than that of normal tissue[(2.547±1.370)vs(1.330±0.831),P＜0.01],and was associated with greater omentum metastasis,lymph node metas-tasis,FIGO staging,and survival(P＜0.01).Knocking down the FUT8-AS1 gene can inhibit the in vitro proliferation and in-vasion ability of epithelial ovarian cancer cell line CAOV3(P＜0.01 or P＜0.05).The results of dual luciferase reporter gene detection showed that co transfection with miR-142-5p mimics and FUT8-AS1-WT plasmids significantly reduced the luciferase activity of CAOV3 cells(P＜0.05).Transfection with miR-142-5p mimics could offset the downregulation of BCL2 gene ex-pression caused by knocking down FUT8-AS1 in CAOV3 cells(P＜0.05).Conclusion The FUT8-AS1 gene is highly ex-pressed in EOC and leads to poor prognosis.Knocking down the FUT8-AS1 gene can inhibit the in vitro proliferation,invasion,and EMT of CAOV3 cells.Mechanistically,the FUT8-AS1 gene may promote the progression of EOC by targeting the miR-142-5p/BCL2 molecular axis.

Bowel sounds can reflect the movement and health status of the gastrointestinal tract.However,the traditional manual auscultation method has subjective deviation and is time-consuming and labor-intensive.In order to better assist doctors in diagnosing bowel sounds and improve the reliability and efficiency of bowel sound detection,this study proposed a deep neural network model that combines a residual neural network(ResNet),a bidirectional long short-term memory network(BiLSTM),and an attention mechanism.Firstly,a large number of labeled clinical data was collected using the self-developed multi-channel bowel sound acquisition system,and the multi-scale wavelet decomposition and reconstruction method was used to preprocess the bowel sounds.Then,log Mel spectrogram features were extracted and sent to the network for training.Finally,the performance and effectiveness of the model were evaluated and verified by 10-fold cross-validation and an ablation experiment.The experimental results showed that the precision,recall,and F1 score of the model reached 83%,76%,and 79%,respectively,and it could effectively detect bowel sound segments and locate their start and end times,performing better than previous algorithms.This algorithm can not only provide auxiliary information for doctors in clinical practice but also offer technical support for further analysis and research of bowel sounds.

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Objective To observe the effects of acupuncture on spatial learning and memory ability,gut flora composition,intracerebral lipopolysaccharide content,and blood-brain barrier permeability in APP/PS1 mice.To explore the intrinsic mechanism of acupuncture in the treatment of Alzheimer′s disease.Methods 24 APP/PS1 mice were randomly divided into the model group,acupuncture group,and probiotic group,and 8 C57BL/6 mice of the same background were used as the normal control group.In the acupuncture group,acupuncture points were taken from"Baihui","YinTang",and"Zusanli"for 20 min.In the probiotic group,probiotics were given by gavage.The model group and normal control group received only restraint.The above interventions were performed once a day for 45 days.After 45 days of intervention,the feces of mice in each group were taken for 16s RNA,and spatial learning and memory skills in each group were observed by the Morris water maze test.The Lipopolysaccharide(LPS)in the brain was detected by immunofluorescence.The blood-brain barrier(BBB)structure was observed by transmission electron microscopy.Results Compared to the model group,Acupuncture improved the spatial learning and memory ability of APP/PS1 mice(P<0.05).It regulated species diversity and composition of APP/PS1 mice,and LPS was significantly decreased(P<0.05).Conclusion Acupuncture significantly improved spatial learning and memory in APP/PS1 mice,modulated BBB tight junction structure,and reduced hippocampal neuronal degeneration,and the effects were consistent with probiotics.The intrinsic mechanism of action is probably achieved by regulating intestinal flora and reducing LPS load.

OBJECTIVES: This study aims to investigate the effects of tumor-stromal fibroblasts (TSFs) on the proliferation, invasion, and migration of salivary gland pleomorphic adenoma (SPA) cells in vitro. METHODS: Salivary gland pleomorphic adenoma cells (SPACs), TSFs, and peri-tumorous normal fibroblasts (NFs) were obtained by tissue primary culture and identified by immunocytochemical staining. The conditioned medium was obtained from TSF and NF in logarithmic phase. SPACs were cultured by conditioned medium and treated by TSF (group TSF-SPAC) and NF (group NF-SPAC). SPACs were used as the control group. The proliferation, invasion, and migration of the three groups of cells were detected by MTT, transwell, and scratch assays, respectively. The expression of vascular endothelial growth factor (VEGF) in the three groups was tested by enzyme linked immunosorbent assay (ELISA). RESULTS: Immunocytochemical staining showed positive vimentin expression in NF and TSF. Results also indicated the weak positive expression of α-smooth muscle actin (SMA) and fibroblast activation protein (FAP) in TSFs and the negative expression of α-SMA and FAP in NFs. MTT assay showed that cell proliferation in the TSF-SPAC group was significantly different from that in the NF-SPAC and SPAC groups (P<0.05). Cell proliferation was not different between the NF-SPAC and SPAC groups (P>0.05). Transwell and scratch assays showed no difference in cell invasion and migration among the groups (P>0.05). ELISA showed that no significant difference in VEGF expression among the three groups (P>0.05). CONCLUSIONS TSFs may be involved in SPA biological behavior by promoting the proliferation of SPACs but has no effect on the invasion and migration of SPACs in vitro. Hence, TSF may be a new therapeutic target in SPA treatment.
Humans ; Adenoma, Pleomorphic/metabolism* ; Vascular Endothelial Growth Factor A ; Culture Media, Conditioned/metabolism* ; Fibroblasts/metabolism* ; Salivary Glands/metabolism*

【Objective】 To study the effects of miR-30e-5p from bone marrow mesenchymal stem cell-derived exosomes(BMSC-exos) on high glucose (HG)-induced HK-2 cell pyroptosis and explore an alternative strategy to manage diabetic kidney disease (DKD). 【Methods】 BMSC-exos were isolated and internalized into HK-2 cells treated with HG to measure viability and cytotoxicity. The secretion of IL-1β and IL-18 was measured by ELISA. Pyroptosis was assessed by flow cytometry. The levels of miR-30e-5p, IL-1β, and IL-18 were measured. The expression of pyroptosis-associated cytokine proteins was determined. 【Results】 BMSC-exos decreased LDH, IL-1β, and IL-18 secretion and inhibited the expression of the pyroptosis-related factors (IL-1β, caspase-1, GSDMD-N, and NLRP3) in HG-induced HK-2 cells. Moreover, miR-30e-5p depletion in BMSC-exos promoted HK-2 cell pyroptosis. 【Conclusion】 BMSC-derived exosomal miR-30e-5p inhibits caspase-1-mediated pyroptosis in HG-induced HK-2 cells, which might provide a new strategy for treating DKD.

Objective:To study the dimensions and contents of COVID-19 prevention and control in primary medical institutions. emergency response capabilities for primary medical institutions review the policy documents about epidemic prevention and control in primary medical institutions issued by China health administrative department, are extracted.Methods:The policy documents related to epidemic prevention and control in primary medical institutions were searched from official websites of The State Council, National Health Commission of the People′s Republic of China and its subordinate agencies from January 2020 to June 2023;"primary medical institutions""community health service institutions""community hospitals""public health emergencies""infectious diseases""emergency response""prevention and control", and"epidemic prevention and control"were used as search keywords. The contents related to epidemic prevention and control in primary medical institutions were extracted and further classified according to the theory of emergency management.? Results ?The policy contents covered three stages: pre-prevention, in-process response, and post-recovery, among which the contents related to the post-recovery stage were relatively less. The word frequency analysis extracted a total of 16 content dimensions, among which department collaboration (16/125), case discovery reports (15/125), hospital infection prevention and control (14/125), community residents′ health education (12/125), and material reserves (11/125) were the top 5 in terms of frequency. Conclusion:The policies related to the prevention and control of COVID-19 in primary medical institutions cover three stages. At different stages of the development of major infectious diseases, measures are taken according to policy requirements.