Objective:To discuss the role of changes of serum total bile acid(TBA)levels induced by long-term high-fat diet in the occurrence of supraventricular arrhythmia(SVA)in the apolipoprotein E knockout(ApoE-/-)mice,and to clarify its mechanism.Methods:Twenty ApoE-/-mice were randomly divided into normal diet group and high-fat diet(HFD)group(n=10);after 20 weeks of feeding,surface electrocardiogram was used to detect cardiac electrophysiology of the mice in various groups;echocardiography was used to detect cardiac systolic function and structure in the mice in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of blood lipids,total bile acid(TBA)and inflammatory factors in the mice in various groups;hematoxylin-eosin(HE)staining was used to detect cardiac inflammatory response in the mice in various groups;Masson staining was used to observe myocardial fibrosis degree in the mice in various groups.Results:Compared with normal diet group,4 cases of junctional premature beat(JPB)/junctional tachycardia(JT),1 case of premature atrial contraction(PAC)and 1 case of premature ventricular contraction(PVC)were found in HFD group,while only 1 case of JPB/JT and 1 case of PAC were found in normal diet group.Compared with normal diet group,the heart rate of the mice in HFD group was significantly decreased(P<0.05);the QRS and QT intervals were significantly prolonged(P<0.05);the ejection fraction(EF)and fractional shortening(FS)were significantly decreased(P<0.05);the end-diastolic volume(EDV)was increased(P<0.05),but there was no significant difference in end-systolic volume(ESV)between groups(P>0.05);the left ventricular internal diameter at end-diastole(LVIDd)and left ventricular internal diameter at end-systole(LVIDs)were significantly increased(P<0.05).There were no significant differences in plasma total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDL-c)and low-density lipoprotein(LDL-c)levels and body weight between normal diet group and HFD group(P>0.05).Compared with normal diet group,the TBA level of the mice in HFD group was significantly increased(P<0.05).There were no significant differences in interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),and C-X-C motif chemokine ligand 1(CXCL-1)levels between HFD group and normal diet group.Compared with normal diet group,the interleukin-1β(IL-1β)level in HFD group showed an increasing trend,but there was no significant difference between groups(P>0.05).The HE staining results showed that the inflammatory cell infiltration was similar between HFD group and normal diet group.The Masson staining results showed that compared with normal diet group,the fibrosis of the mice in HFD group showed an increasing trend,but there was no significant difference in myocardial fibrosis area between groups(P>0.05).Conclusion:Long-term high-fat diet may increase serum TBA level in ApoE-/-mice,which may induce SVA.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective:To explore the surgical intervention strategy for metastatic cervical lymph nodes surrounding the carotid artery in head and neck squamous cell carcinoma.Methods:A total of 62 patients with advanced head and neck tumors and carotid wrap by disease treated in Department of Otorhinolaryngology and Head and Neck Surgery, the Affiliated BenQ Hospital of Nanjing Medical University between June 2019 and December 2023 were reviewed, of whom 9 patients presented with metastatic squamous cell carcinoma in cervical lymph nodes of unknown primary or with no recurrence of primary lesion and all the 9 patients were males, aged from 48 to 79 years old, with≤level 2 of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS). Radiographically common carotid artery (CCA) and/or internal carotid artery (ICA) were surrounded by≥270° with tumor. All the 9 patients received implantation of covered stent in carotid artery and radical resection of metastatic cervical lymph nodes. The success rate, complications, surgery-related complications, local recurrence rate, quality of life (QOL) and overall survival (OS) were analyzed. The QOL of patients was compared by paired rank sum test, and P<0.05 indicated statistically significant difference. The OS was analyzed by Kaplan-Meier. Results:The success rate of stent implantation was 100%, with no implantation-related complications. R0 resection was performed in 8 cases and R1 resection in 1 case. The QOL of patients after surgery was improved, and the improvements in "pain", "mood" and "anxiety" were statistically significant( Z values were -2.236, -2.460 and -2.200, respectively, and all P values were<0.05). Follow-up was 1-18 months, with a median of 7 months, and 1 case was lost to follow-up. Local recurrence occurred in 3 patients with an incidence of 37.5% (3/8). OS was 59.9% at 12 months after surgery. Conclusion:Implantation of covered stent in carotid artery combined with radical resection is an effective method for the treatment of cervical lymph node metastasis.

Objective To observe the value of transesophageal echocardiography(TEE)for guiding left atrial appendage closure(LAAC)with LAmbre occluder.Methods Data of 40 non-valvular atrial fibrillation(NVAF)patients who underwent LA AC with LAmbre occluder were retrospectively analyzed.CT angiography(CTA)before treatment,TEE and digital subtraction angiography(DSA)findings during LAAC were comparatively observed,and the correlations of the anchor area diameter and left atrial appendage opening diameter measured with the above three as well as occluder size were analyzed,and TEE and DSA for evaluating peri-device leak(PDL)were compared.Results LAAC were successfully performed with LAmbre occlude in all 40 cases.The diameter of the fixed umbrella was positively correlated with anchor area diameter measured with CTA,TEE and DSA(r=0.79,0.82,0.91,all P＜0.01),of occlusion umbrella was positively correlated with left atrial appendage opening diameter measured with CTA,TEE and DSA(r=0.56,0.89,0.86,all P＜0.01).Immediately after the release of occluder in LAAC,PDL occurred in 16 cases and were detected with both TEE and DSA,while in the rest 24 cases no PDL was found with neither TEE nor DSA.Conclusion TEE had comparable value to DSA for guiding LAAC using LAmbre occluder.

Liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment options.Here,we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies,ephedrine inhalation,intravenous use of methylene blue with nitric oxide(NO)inhalation,and NO inhalation alone.The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury.Early initiation of NO inhalation,rather than ephedrine,can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications.Therefore,based on the response to these exploratory salvage treatments,we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS.We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.

Objective To construct and validate a risk prediction model for poor inhalation in chronic obstructive pulmonary disease(COPD)patients receiving inhaler therapy,providing a decision support tool for personalized prevention of poor inhalation.Methods A cross-sectional study was conducted to collect data related to COPD patients receiving inhaler therapy,forming a dataset.The dataset was randomly divided into a training set and a test set in a ratio of 4∶1.Four different methods for missing value imputation,3 methods for variable feature selection,and 18 machine learning algorithms were employed to successfully construct 216 models on the training set.The monte carlo simulation method was used for resampling in the test set to validate the models,with the area under curve(AUC),accuracy,precision,recall,and F1 score used to evaluate model performance.The optimal model was selected to build the poor inhalation prediction platform.Results A study involving 308 patients with COPD found that 135(43.8%)were at risk of adverse inhalation.Using 33 predictor variables,216 risk prediction models were developed.Of these models,the ensemble learning algorithm yielded the highest average AUC of 0.844,with a standard deviation of 0.058[95%CI=(0.843,0.845)].The differences in predictive performance among the 216 models were statistically significant(P＜0.01).Under the ensemble learning algorithm,adherence to inhaler use(38.087 4%),inhaler satisfaction(25.680 1%),literacy(24.031 3%),number of inhalers(5.482 3%),age(4.204 5%)and number of acute exacerbations in the past year(2.184 7%)contributed most to the predictive model.The model exhibited superior performance,with an AUC of 0.869 3,an accuracy of 83.87%,a precision of 86.96%,a recall of 74.07%,and an F1 score of 0.8.Conclusion This study has developed a predictive model for poor inhalation risk in COPD inhaler therapy patients using machine learning algorithms,which exhibits strong predictive capabilities and holds potential clinical application value.

Objective To imporve the service level of integrated outpatient department for cardio-oncology in healthcare facilities,and to improve and optimize pharmaceutical management within cardio-oncology integrated outpatient department.Methods Clinical issues were identified using the Delphi method.Relevant problems and existing evidence were collected and organized through systematic research.The evidence grading and recommendation intensity standards developed by the Center for Evidence-Based Medicine at Oxford University were applied to complete the evidence grading.Through questionnaire consultations with 38 experts.Results A total of 11 clinical questions were identified as consensus items.Based on these issues,expert consensus recommendations for pharmaceutical management in combined cardio-oncology outpatient departments were formulated through evidence retrieval,synthesis,and grading.Ultimately,an expert consensus on pharmaceutical management in combined cardio-oncology outpatient clinics was established.Conclusion The expert consensus serves as a reference for managing combined clinical cardio-oncology outpatient clinics,significantly contributing to offering more professional and comprehensive diagnosis and treatment services for cancer patients.

Lumbar disc herniation is mainly manifested as lower back pain,numbness,weakness,and radiating pain in the lower limbs,which seriously affects the patients'work and quality of life.In clinical practice,it has been found that this disease always belongs to the category of deficiency in healthy qi and excess in pathogenic factors,often accompanied by kidney deficiency and cold dampness.Kidney deficiency is the root cause,while cold dampness is the symptoms.The two factors interact with each other and cause back pain.The treatment is based on dispersing cold and dampness,tonifying the kidneys and strengthening the waist,and the classic ancient formula Shenzhuo Powder is safe and effective.

Objective To investigate the effect of perineal nerve electroacupuncture combined with tolterodine in the treatment of female overactive bladder(OAB).Methods A total of 150 female OAB patients treated in Huzhou Hospital of Traditional Chinese Medicine,Zhejiang Chinese Medical University from April 2020 to May 2021 were selected and divided into control group and study group according to random number table method,with 75 cases in each group.The control group was treated with tolterodine,and the study group was treated with pudendal nerve electroacupuncture combined with tolterodine.Clinical symptoms,urinary symptoms,and urodynamic indicators[maximum cystometric capacity(MCC),maximum urethral closure pressure(Pura clos max),maximum detrusor pressure(Pdet max),and maximum urine flow rate(Qmax)],bladder function indicators(initial bladder sensation volume,bladder volume during strong micturition desire),nerve growth factor(NGF)mediated transient receptor potential(TRP)pathway indicators[NGF,NGF/urine creatinine(UCr),TRPV1,TRPV4]and clinical efficacy of two groups were compared.Results After treatment,the number of night urination and urgent urination in study group were significantly less than those in control group,and the average volume of urination was significantly more than that in control group(P＜0.05).The overactive bladder symptom scores and visual analogue scale scores of study group were significantly lower than those of control group(P＜0.05).The MCC and Pura·clos·max in study group were significantly higher than those in control group,while Pdet max and Qmax were significantly lower than those in control group(P＜0.05).The initial bladder sensation volume and bladder volume during strong micturition desire in study group were higher than those in control group(P＜0.05).NGF,NGF/UCr,positive expression rates of TRPV1 and TRPV4 in study group were lower than those in control group(P＜0.05).The total effective rate was significantly higher in study group than in control group,(x2=5.374,P=0.020).There was no significant difference in the incidence of total adverse reactions between two groups(x2=0.362,P=0.547).Conclusion Perineal nerve electroacupuncture combined with tolterodine can significantly improve bladder function and inhibit clinical symptoms in female OAB patients,possibly by inhibiting bladder sensitivity caused by NGF-mediated increase of TRP channel proteins TRPV1 and TRPV4.

Objective:To explore the effects of dexmedetomidine (DEX) on intestinal stress response and cellular immune function in patients with gynecologic malignancies undergoing laparoscopic surgery.Methods:A total of 60 patients with gynecologic malignancies who scheduled to undergo laparoscopic surgery under general anesthesia in the Second Hospital of Shanxi Medical University from March 2021 to March 2022 were selected. All patients were divided into the DEX group and the control group according to the random number table method, with 30 cases in each group. The DEX group included 12 cases of cervical cancer, 10 cases of endometrial cancer and 8 cases of ovarian cancer; the control group included 14 cases of cervical cancer, 9 cases of endometrial cancer and 7 cases of ovarian cancer. The DEX group: intravenous anesthesia was induced with a dose of DEX 0.5 μg/kg (infusion was completed within 10 min), general anesthesia was maintained with DEX 0.2 μg·kg -1·h -1 pumped intravenously, and the drug was stopped 30 min before surgery. The control group: equal amount of 0.9% sodium chloride solution was pumped intravenously. The venous blood was drawn at the time points of 10 min before general anesthesia (T 0), at the end of operation (T 1) and 1 d after the operation (T 2) to detect the stress response indicators such as cortisol (COR), epinephrine (E), norepinephrine (NE) levels, and immune indicators such as CD4 +, CD8 + proportions and CD4 +/CD8 + at T 0, T 1,and T 2. In addition, the pneumoperitoneum time, general anesthesia time, operation time and intestinal function recovery time were recorded. Results:At T 0, there were no statistically significant differences in the levels of COR, E and NE between the DEX group and the control group (all P > 0.05). At T 1, the levels of COR, E and NE were (146±12) μg/L, (158±14) ng/L, (265±12) ng/L, respectively in the control group, and (136±18) μg/L, (149±15) ng/L, (158±12) ng/L, respectively in the DEX group; the levels of COR, E and NE in the DEX group were lower than those in the control group ( t values were -2.51, -2.37, -2.08, all P < 0.05). At T 2, the levels of COR, E and NE were (124±12) μg/L, (131±16) ng/L, (234±8) ng/L, respectively in the control group, and (116±15) μg/L, (123±12) ng/L, (228±10) ng/L, respectively in the DEX group; the levels of COR, E and NE in the DEX group were also lower than those in the control group ( t values were -2.35, -2.23, -2.17, all P < 0.05). At T 0, there were no statistically significant differences in the proportions of CD4 +, CD8 + and CD4 +/CD8 + between the DEX group and the control group (all P > 0.05). At T 1, the proportions of CD4 +, CD8 + and CD4 +/CD8 + were (23±3)%, (20±3)%, 1.12±0.16, respectively in the control group, and (27±4)%, (23±4)%,1.22±0.19, respectively in the DEX group; the proportions of CD4 +, CD8 + and CD4 +/CD8 + in the DEX group were higher than those in the control group ( t values were -3.43, -2.29, 2.13, all P < 0.05). At T 2, the proportions of CD4 +, CD8 + and CD4 +/CD8 + were (26±3)%, (23±4)%, 1.17±0.16, respectively in the control group, and (31±5)%, (25±4)%, 1.26±0.19, respectively in the DEX group; the proportions of CD4 +, CD8 + and CD4 +/CD8 + in the DEX group were higher than those in the control group ( t values were -4.32, -2.02, 2.02, all P < 0.05). In addition, the time of first exhaust in the DEX group was shorter than that in the control group ( P<0.05). Conclusions:DEX can reduce the intestinal stress response of gynecologic malignancies patients undergoing laparoscopic surgery, thereby improving the immunosuppression of patients. It is also of great significance to protect intestinal mucosal barrier and recover the intestinal function, and DEX has a high safety.