OBJECTIVE To explore the effects and potential mechanism of Huangqi jianzhong decoction on intestinal inflammation in the rats of irritable bowel syndrome with diarrhea （IBS-D） based on the mitogen-activated protein kinase （MAPK）/ nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were selected. Ten rats were randomly chosen as the control group， and the remaining rats （50 rats） were used to prepare the IBS-D model by acetic acid enema+restraint stress. The rats with successful modeling were randomly divided into the IBS-D group， the traditional Chinese medicine （TCM） group （Huangqi jianzhong decoction 15 g/kg）， the positive control drug group （Rifaximin tablets 150 mg/kg）， the activator group （anisomycin 125 μg/kg， the activator of p38 MAPK）， and the TCM+activator group （Huangqi jianzhong decoction 15 g/kg+ anisomycin 125 μg/kg）， with 10 rats in each group. Rats in each group were given a gavage or tail vein injection of the corresponding medicine liquid or the same volume of normal saline， once a day for two consecutive weeks. After the last administration， feces within 24 hours were collected for the calculation of fecal water content and fecal trait score， and the minimum volume threshold was detected. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in serum were detected； the pathological changes of colonic tissue were observed； the expressions of tight junction protein ZO-1， occludin mRNAs and proteins related to the MAPK/NF- κB signaling pathway in colonic tissue were determined. RESULTS Compared with the control group， obvious edema and inflammatory cell infiltration could be observed in the colonic tissue of rats in the IBS-D group. The fecal water content and trait score， serum levels of inflammatory factors， as well as the protein phosphorylation levels of p38 MAPK and NF-κB p65 in the colonic tissue were significantly increased， while the minimum volume threshold and the mRNA expressions of ZO-1 and occludin were significantly decreased or down-regulated （P＜0.05）. Compared with the IBS-D group， the pathological changes of colonic tissue in the TCM group and positive control drug group were alleviated， and the above indicators improved significantly （P＜0.05）， while the above indicators in the activator group deteriorated further （P＜0.05）. Compared with the TCM group， the above indicators in the TCM+activator group were significantly reversed （P＜0.05）. CONCLUSIONS Huangqi jianzhong decoction can alleviate colonic inflammation in IBS-D rats， relieve visceral hypersensitivity， and has a certain protective effect on their intestinal barrier function. The above-mentioned effects may be related to the inhibition of the MAPK/NF- κB signaling pathway.

ObjectiveTo multidimensionally analyze the clinical effects of Qianyang Yuyin granules on elderly hypertensive patients through an "energy-inflammation-aging" network. MethodsRelevant datasets were retrieved from the GEO database. Gene set enrichment analysis （GSEA） was performed on the gene expression profiles of peripheral blood cells from patients with essential hypertension in dataset GSE24752. The GSEA referenced "GO gene sets" and "KEGG gene sets" to identify significantly enriched gene sets. A clinical trial was conducted using a randomized controlled study design. A total of 40 patients meeting the inclusion criteria were enrolled. The control group received standard antihypertensive treatment with angiotensin receptor blockers （ARBs） or combined calcium channel blockers （CCBs）. In contrast，the treatment group received Qianyang Yuyin Granules in addition to the standard treatment for 12 weeks. Blood pressure levels and clinical efficacy were observed，and changes in energy metabolism indicators，DNA damage markers，and senescence-associated secretory phenotype （SASP） in blood were measured using ELISA before and after treatment. ResultsGSEA results indicated significant energy metabolism dysregulation in hypertensive patients. Clinical findings showed that both groups achieved blood pressure control without significant intergroup differences. In terms of clinical efficacy，the treatment group had a significantly higher effective rate compared to the control group （95% vs 65%，P0.05）. After treatment，the treatment group showed a significant increase in NAD⁺ levels （P0.01），with higher levels compared to the control group （P0.05）. The treatment group also exhibited a greater reduction in DNA damage marker 8-OHdG （P0.01） and cell adhesion factors ICAM-1 and VCAM-1 （P0.01） compared to the control group. Pro-inflammatory cytokines IL-1β and IL-6 were significantly reduced in the treatment group （P0.01），with greater reductions compared to the control group （P0.05，P0.01）. Anti-inflammatory cytokines IFN-α，IL-4，and IL-10 were significantly elevated in the treatment group （P0.01），with higher levels compared to the control group （P0.01）. No significant adverse reactions were reported in either group. ConclusionThe "energy- inflammation- aging" network plays an important role in the pathological mechanism of hypertension patients. Qianyang Yuyin granules may delay the aging process by increasing patients' energy metabolism levels，reducing DNA oxidative damage，and maintaining the balance of inflammatory factors.

Objective To investigate the effects of Fuzheng Quxie Prescription(mainly with the actions of supporting healthy qi and dispelling pathogens)combined with neoadjuvant chemotherapy on tumor recurrence,serum thymidine kinase 1(TK1)level and immune function in patients with triple-negative breast cancer(TNBC).Methods Eighty patients with TNBC of qi and yin deficiency type were randomly divided into a combination group and a control group,with 40 patients in each group.The control group was treated with AC-T sequential chemotherapy(Doxorubicin combined with Cyclophosphamide plus sequential Docetaxel),and the combination group was treated with Fuzheng Quxie Prescription on the basis of treatment for the control group.One course of treatment covered 21 days,and the two groups were treated for 4 consecutive courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,levels of tumor markers of carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and TK1,and T lymphocyte subset levels in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and tumor metastasis and recurrence in the two groups were compared.Results(1)After 4 courses of treatment,the total effective rate of the combination group was 87.50%(35/40),and that of the control group was 67.50%(27/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the combination group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the KPS scores were significantly increased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores and the increase of KPS scores in the combination group were significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the serum CA125,CA153 and TK1 levels of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of serum CA125,CA153 and TK1 levels in the combination group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio in the two groups were significantly increased compared with those before treatment(P＜0.05),and the CD8+ level was significantly decreased compared with that before treatment(P＜0.05).The post-treatment intergroup comparison showed that the increase of the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio as well as the decrease of the CD8+ level in the combination group was all significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The one-year follow-up showed that the tumor recurrence rate and tumor metastasis rate in the combination group were 7.50%(3/40)and 12.50%(5/40)respectively,significantly lower than 25.00%(10/40)and 35.00%(14/40)in the control group,and the differences were statistically significant when comparing between the two groups(P＜0.05).Conclusion The combination of neoadjuvant chemotherapy with Fuzheng Quxie Prescription has a better therapeutic effect on TNBC patients with qi and yin deficiency syndrome,which can effectively improve the immune function of the patients,decrease the level of serum tumor markers,improve the quality of life of the patients,and reduce the incidence of tumor recurrence and metastasis.

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

Objective To analyze the frailty of patients with long-term maintenance dialysis(MD)and its influencing factors,and to explore the correlation of different dialysis modalities with the re-infection of novel coronavirus infection(COVID-19)and frailty syndrome.Methods Patients with regular dialysis in Nephrology Department of the Second Affiliated Hospital of Kunming Medical University from February to June 2023 were selected.A cross-sectional survey was conducted to collect clinical data of the patients,including dialysis modality(i.e.maintenance hemodialysis,abbreviated as hemodialysis,and continuous ambulatory peritoneal dialysis,abbreviated as peritoneal dialysis),and whether with re-infection of COVID-19.Patients were divided into 3 groups using Fried's frailty phenotype(FP):non-frailty group,pre-or-intermediate frailty group,and frailty syndrome group.The clinical characteristics of the FP were compared among the three groups.The correlation of frailty with clinical data,dialysis modality,re-infection of COVID-19 in each group was compared.Multifactorial logistic regression was used to analyze the factors influencing the development of frailty syndrome in patients.Results A total of 246 dialysis patients were included in this study,with 77(31.3%)in the non-frailty group,83(33.7%)in the pre-frailty group and 86(35.0%)in the frailty syndrome group.The frailty syndrome group showed characteristics of advanced age,high pre-dialysis creatinine level,low serum albumin level and combined pleural effusion(all P＜0.05).There was no statistically significant difference in the comparison of frailty between the hemodialysis and peritoneal dialysis group(P = 0.960).COVID-19 re-positive patients had higher frailty score than non-re-positive patients.Multifactor logistic regression showed that age,COVID-19 re-infection of COVID-19,serum albumin,pre-dialysis creatinine,and pleural effusion were factors influencing the development of frailty syndrome in dialysis patients(P＜0.05).Conclusion There is high incidence of frailty syndrome in dialysis patients,and there is no correlation of frailty with dialysis modality.High serum albumin level is a protective factor for the development of frailty syndrome in patients,whereas re-infection of COVID-19,advanced age,high pre-dialysis blood creatinine level and pleural effusion are risk factors for the development of frailty syndrome.

ObjectiveTo observe the effects of Youguiwan on bone metabolism and bone morphogenetic protein-2 （BMP-2）/Smad signaling pathway in ovaries-removed rats with osteoporosis and study the mechanism of Youguiwan in the prevention and treatment of osteoporosis. MethodA postmenopausal rat model of osteoporosis was prepared by bilateral ovariectomy. The 40 female SD rats were randomly divided into five groups， including sham operation group， model group， alendronate sodium group （0.1 mg·kg^-1）， and high-dose and low-dose （5.36 and 2.68 g·kg^-1） groups of Youguiwan. The drug was given seven days after modeling， once a day for 12 weeks. After the treatment， the changes in femur tissue structure were observed by micro-CT， including bone mineral density （BMD）， bone volume/total volume （BV/TV）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， bone surface/bone volume （BS/BV）， and trabecular separation （Tb.Sp）. Ossification was observed by saffrane-solid green staining， and serum levels of bone metabolism markers， including bone alkaline phosphatase （BALP）， osteocalcin （BGP）， type Ⅰ procollagen amino terminal propeptide （PINP）， and tartrate-resistant acid phosphatase 5b （TRACP-5b）， were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression levels of Runx2， BMP-2， and Smad1 in rat femur were detected by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the sham operation group， bone trabecula in the model group was sparse. BMD， BV/TV， Tb.N， and Tb.Th were decreased （P<0.05， P<0.01）. BS/BV （P<0.05） and Tb.Sp were increased. The content of BGP， BALP， PINP， and TRACP-5b in serum was significantly increased （P<0.01）. The mRNA and protein expressions of Runx2， BMP-2， and Smad1 in rat femur were significantly decreased （P<0.05， P<0.01）. Compared with the model group， the number of bone trabeculae in the high-dose and low-dose groups of Youguiwan was increased， and the bone microstructure was improved. BMD， BV/TV， Tb.N， and Tb.Th were increased significantly （P<0.05， P<0.01）， and BS/BV and Tb.Sp were increased. The content of bone metabolic markers decreased （P<0.05， P<0.01）. ConclusionYouguiwan has certain preventive and therapeutic effects on postmenopausal osteoporosis， and its mechanism may be related to promoting bone formation by regulating the BMP-2/Smad signaling pathway.

OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

The “hospital-community” hospice care model involves multiple stakeholders，including demander，executor，leader，and fundraiser of medical and health services.The degree of benefit correlation，policy influence，and implementation willingness of various stakeholders were analyzed to provide reference for terminal cancer patients to obtain continuous，convenient，and high-quality hospice care.Health department and medical insurance department are the main driving forces for cross-institutional hospice care，but there are differences in their driving paths.The financial department is an important guarantor of policy implementation，and needs to ensure that its core interests are not lost.Community medical institutions are an important driving factor for policy implementation，but they require policy support and hospital drive. Medical staff in hospitals and communities，have weak willingness to implement policies，which can easily become obstacles to policy implementation in the absence of incentive and compensation mechanisms.Patients and their caregivers are important beneficiaries，but lack of publicity，education，and interactive communication can also lead to rejection and contradiction.Therefore，it is necessary to leverage the collaboration and coordination between policy enforcement departments，innovate the development model of hospitals，lead community medical institutions，and promote interactive communication and decision-making sharing of “doctor-doctor” and “doctor-patient”.

Plasmodium falciparum malaria, caused by Plasmodium falciparum infection, is an Anopheles mosquito-transmitted infectious diseases, which predominantly occurs in tropical areas of Africa. P. falciparum malaria is characterized by complex and atypical clinical manifestations, and high likelihood of misdiagnosis and missing diagnosis, and may be life-threatening if treated untimely. This case report presents the diagnosis and treatment of a P. falciparum malaria case with acute abdominal pain as the first symptom.