OBJECTIVES: To explore the mechanism of Pingchuanning Formula (PCN) for inhibiting airway inflammation in rats with asthmatic cold syndrome. METHODS: A total of 105 SD rats were randomized equally into 7 groups, including a control group, an asthmatic cold syndrome model group, 3 PCN treatment groups at high, medium and low doses, a Guilong Kechuanning (GLCKN) treatment group, and a dexamethasone (DEX) treatment group. In all but the control rats, asthma cold syndrome models were established and daily gavage of saline, PCN, GLCKN or DEX was administered 29 days after the start of modeling. The changes in general condition, lung function and lung histopathology of the rats were observed, and inflammatory factors in the alveolar lavage fluid (BALF), oxidative stress, lung tissue ultrastructure, cytokine levels, and expressions of the genes related to the HMGB1/Beclin-1 axis and autophagy were analyzed. RESULTS: The rat models had obvious manifestations of asthmatic cold syndrome with significantly decreased body mass, food intake, and water intake, reduced FEV_0.3, FVC, and FEV_0.3/FVC, obvious inflammatory cell infiltration in the lung tissue, and increased alveolar inflammation score and counts of neutrophils, eosinophils, lymphocytes, macrophages, and leukocytes in the BALF. The rat models also had significantly increased MDA level and decreased SOD level and exhibited obvious ultrastructural changes in the lung tissues, where the expressions of HMGB1, Beclin-1, ATG5, TNF-α, IL-6,IL-1β, and IL-13 and the LC3II/I ratio were increased, while the levels of Bcl-2 and IFN-γ were decreased. PCN treatment significantly improved these pathological changes in the rat models, and its therapeutic effect was better than that of GLKCN and similar to that of DEX. CONCLUSIONS PCN can effectively alleviate airway inflammation in rat models of asthmatic cold syndrome possibly by modulating the HMGB1/Beclin-1 signaling axis to suppress cell autophagy, thereby attenuating airway inflammatory damages.
Animals ; Rats ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Asthma/pathology* ; Beclin-1 ; HMGB1 Protein/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Male ; Lung/pathology* ; Inflammation

Objective To summarize the clinical experience of the treatment for complex aortic coarctation with extra anatomic bypass and anatomic correction techniques. Methods The clinical data of patients with complex aortic coarctation treated in the First Affiliated Hospital of Nanjing Medical University and Friendship Hospital of Ili Kazakh Autonomous Prefecture between April 2012 and November 2020 were retrospectively reviewed. Results A total of 12 patients were enrolled, including 5 males and 7 females aged 11-54 (34.3±16.2) years. Extra anatomic bypass grafting was performed in 8 patients and anatomic correction was performed in 4 patients. The operations were successful in all patients. There was no perioperative death. The average cardiopulmonary bypass time was 203.0±46.0 min (7 median incision patients), and the average intraoperative blood loss was 665.0±102.0 mL. The average postoperative ventilator support time was 32.3±7.5 h, and the average postoperative hospital stay time was 10.2±4.3 d. The mean drainage volume of median incision was 1 580.0±360.0 mL, and the mean drainage time was 9.3±2.7 d. The mean drainage volume of left thoracotomy was 890.0±235.0 mL, and the mean drainage time was 4.8±2.5 d. One patient had a transient hoarse after operation and recovered 6 months later. The follow-up period ranged from 2 to 10 years with an average time of 81.0±27.0 months. All patients had a recovery of hypertension, cardiac afterload after 2 years postoperatively. One patient who received an artificial blood vessel replacement in situ was examined stenosis recurrence at the third year after discharge. Others were asymptomatic during the follow-up period. There were no death or other complications. Conclusion The treatment strategy for complex aortic coarctation should be individualized according to the anatomical features and concomitant heart diseases. Extra anatomic bypass technique is a safe and feasible choice.

ObjectiveTo explore the prevalence and influencing factors of multimorbidity among the HIV-infected individuals receiving anti-viral therapy (ART) in Dehong Prefecture of Yunnan Province, so as to provide a reference for the long-term follow-up management of HIV-infected patients and the comprehensive prevention and treatment of chronic diseases. MethodsA cross-sectional study was conducted to investigate the multimorbidity burden among the HIV-infected adults receiving ART in Dehong Prefecture from January to July 2021 and a self-designed questionnaire was used to analyze relevant disease indicators. Multivariate logistic regression analysis was used to investigate the influencing factors of multimorbidity among the HIV-infected individuals. ResultsA total of 3 946 HIV-infected individuals receiving ART were enrolled in this study, of which 63.7% aged ≤50 years, with a male to female ratio of 1.1∶1. Among the 3 946 cases, 825 of them had ≥2 comorbidities, with a co-prevalence rate of 20.9% (95%CI:19.6%‒22.2%), and the main comorbidities were dyslipidemia, diabetes, and hypertension. Multivariate logistic regression analysis showed that 40≤ aged <50 years (aOR=1.86, 95%CI: 1.45‒2.40, P<0.001), 50≤ aged ≤85 years (aOR=3.75, 95%CI: 2.93‒4.80, P<0.001), Dai nationality (aOR=1.21, 95%CI: 1.01‒1.47, P=0.043), BMI≥24.0 kg∙m^-2 (aOR=1.79, 95%CI: 1.49‒2.14, P<0.001), 10.0≤ with ART duration for <12.5 years (aOR=1.49, 95%CI: 1.05‒2.12, P=0.024), with ART duration for ≥12.5 years (aOR=1.50, 95%CI: 1.05‒2.15, P=0.026), use of second-line HIV therapy (aOR=1.43, 95%CI: 1.19‒1.70, P<0.001) and other therapy options (aOR=3.16, 95%CI: 2.17‒4.61, P<0.001) were positively correlated with multimorbidity. ConclusionThe prevalence of multimorbidity among the HIV-infected individuals receiving ART in Dehong Prefecture is high, which is associated with the advancing age and prolonged treatment time, particularly with a significant burden of dyslipidemia, diabetes, and hypertension. Comprehensive surveillance and targeted management of comorbidities, along with ART follow-up, need to be strengthened in the future.

  Objective  Different from other etiologies of early-onset scoliosis (EOS), congenital early-onset scoliosis (CEOS) is mainly linked to vertebral anomalies, such as formation failures and segmentation failures at the apex segments. So far, there is little research on CEOS patients who have completed traditional growing rods (TGR) treatment, and the initial outcomes of TGR with or without apical control technique (ACT) are different. Therefore, we compared the "final" results of CEOS patients who completed TGR treatment with or without ACT.  Methods  We conducted a retrospective study of CEOS patients who completed TGR treatment from 2007—2020. They either had final fusion or were followed up after reaching skeletal maturity. We split the patients into two groups based on whether they had ACT with TGR or not. The ACT-TGR group had apical vertebrectomy/hemivertebrectomy with short fusion and TGR. The TGR-only group had only TGR. We looked at their demographic features, radiographic measurements, and complications.  Results  This study enrolled 46 CEOS patients, of which 13 patients were in the ACT-TGR group and 33 patients in the TGR group. The ACT-TGR group had a longer distraction interval (1.17 years vs. 0.75 years). The ACT-TGR group had a larger preoperative main curve [87.00(63.50, 98.00)], but the residual curve degrees were comparable between the two groups at the last follow-up (P=0.354). At the last follow-up, the T1-12 and T1-S1 heights were similar between the two groups. The ACT-TGR group had a lower number of implant-related complications per patient (0.77 vs. 1.48). Three patients in the ACT-TGR group underwent final fusion, while 17 patients in the TGR group underwent final fusion (P=0.060).  Conclusions  Both ACT-TGR and traditional TGR coud effectively correct deformity and preserve spinal growth in CEOS patients. ACT-TGR had a better corrective effect on patients with severe deformity and did not have a significant impact on spinal height. For patients with acceptable correction, spontaneous fusion and without implant failure, retaining the implant and continuing observation could be a strategy for graduating from growing rod treatment.

OBJECTIVE：To explore t he mechanism of Xinmaikang improving atherosclerosis （AS）in rabbits. METHODS ：A total of 50 male Zealand rabbits were randomly divided into sham operation group ，model group ，simvastatin group [positive control ， 2.60 mg/（kg·d）] and Xinmaikang low-dose and high-dose groups [ 0.21，0.84 g/（kg·d）]，with 10 rabbits in each group. Rabbits in sham operation group were fed with ordinary diet ，and only femoral artery was separated and ligated ，and abdominal aortic endothelium was not strained ；the other groups were given high-fat diet and received abdominal aortic intimal balloon injury to induce AS model. Ten weeks after operation ，sham operation group and model group were given intragastric administration of normal saline ，and administration groups were given corresponding drug solution intragastrically （normal saline as solvent ）with the volume of 100 mL，once a day ，for consecutive 12 weeks. After last administration ，the pathological changes of abdominal aorta and inner wall in rabbits were observed in each group. The serum contents of triglyceride （TG），total cholesterol （TC），low density lipoprotein cholesterol （LDL-C），high density lipoprotein cholesterol （HDL-C），interleukin-6（IL-6）and IL- 1β were detected，and the contents and protein expression of Toll-like receptor 4（TLR4）and nuclear factor-κB p65（NF-κB p65）in abdominal aortic tissue were determined. RESULTS ：Compared with sham operation group ，the intima of abdominal aorta in model group was rich in lipids ，the thickness of vessel wall and plaque area were increased obviously ，and there was obvious vascular endothelial injury. The contents of TG ，TC，LDL-C，IL-6 and IL- 1β in serum，the contents and protein expression of TLR 4 and NF-κB p65 in abdominal aorta tissue were significantly increased ，while the content of HDL-C was decreased significantly （P＜0.05 or P＜ 0.01）. Compared with model group ，the lesion of rabbit abdominal aorta were alleviated ，and no obvious damage was found on the inner wall. The contents of TG ，TC，LDL-C，IL-6，IL-1β of Xinmaikang high-dose group and simvastatin group as well as the content of NF-κB p65 and protein expression of TLR4 and cnd- NF-κB p65 were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：Xinmaikang can improve AS in rabbits ， and its mechanism may be assicated with inhibiting the expression of TLR 4，NF-κB p65 and inhibiting inflammatory response.

Objective: To explore the postoperative effect, prognosis, and prognostic factors for benign testicular tumors. Methods: We retrospectively analyzed the clinical data of 35 patients with benign testicular tumors between May 2004 and May 2017 from Sun Yat-sen University Cancer Center, and the patients were followed up until October 2017. Results: The mean age of the 35 patients was 18.8 (0.4-44.0) years. Among them, 14 patients (40.0%) underwent testis-sparing surgery and 21 (60.0%) underwent radical orchiecto-my, and the tumor sizes were 1.8 (0.4-4.0) cm and 2.7 (1.0-8.0) cm, respectively. All patients had been cured without obvious perioper-ative complications. Postoperative histopathological tumor types included 18 epidermal cysts, 10 mature teratomas, 4 interstitial cell tumors, and 3 adenomatoid tumors. Frozen section examination of 10 cases had been operated, and all results were consistent with paraffin pathology. No patient who underwent testis-sparing surgery showed recurrence and/or metastasis during follow-up, and their sexual function and fertility were well preserved. Conclusions: Testis-sparing surgery is reliable, and the size of the tumor determines its implementation. An intraoperative rapid frozen section examination should be performed in patients with testicular neoplasms of a benign or variable nature diagnosed before operation. Patients with benign testicular tumors should undergo testis-sparing surgery, whereas others should undergo radical orchiectomy.

Objective To investigate the effects of Xinkang recipe on myocardial collagen metabolism in rats with doxorubi-cin-induced heart failure.Methods Male SD rats were randomly divided into sham operation group(sham group),model group, Xinkang group and captopril group.The rat model of heart failure was established by intraperitoneal injection of doxorubi-cin.Distilled water,Xinkang decoction and captopril were respectively administrated to rats by gavage for 35 d.The indexes of ventricular remodeling and cardiac function were measured.Myocardial fibrosis was assessed by Masson's trichrome stai-ning.The expression levels of collagen Ⅰ,collagen Ⅲ,TGF-β1,IκB and p56 were detected in myocardial tissues by Western blotting.Myocardial protein and mRNA levels of matrix metalloproteinase-2(MMP-2),MMP-9,and tissue inhibitor of matrix metalloproteinase-1(TIMP-1)and TIMP-2 were detected by Western blotting and RT-qPCR,respectively.Results The expres-sion levels of collagenⅠand collagen Ⅲ protein,the collagen volume fraction(CVF),and the expression levels of TGF-β1 and p56 protein were significantly increased(P< 0.01),and the expression level of IκB protein was significantly decreased in the model group as compared with the sham group(P<0.05 for all).The myocardial protein and mRNA levels of MMP-2,MMP-9, TIMP-1,and TIMP-2 were significantly higher in the model group than in sham group(P<0.05 or P<0.01).The cardiac out-put(CO),left ventricular fractional shortening(FS),and left ventricular ejection fraction(LVEF)were significantly lower while the left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),and left ventricular mass index (LVMI)were significantly higher in model group than in sham group(P<0.01).Compared with the model group,the expres-sion levels of collagen Ⅰand collagen Ⅲ protein,the CVF and the TGF-β1 and p56 expression levels were significantly decreased and the IκB protein expression was significantly increased in Xinkang and the captopril groups(P<0.05).The myocardial pro-tein and mRNA levels of MMP-2,MMP-9,TIMP-1,and TIMP-2 were significantly lower in Xinkang and captopril groups than in control group(P<0.05 or P<0.01).CO,FS,and LVEF were significantly higher while LVEDV,LVESV,and LVMI were significantly lower in Xinkang and captopril groups than in model group(P<0.01).Conclusion Xinkang recipe can reduce col-lagen deposition in the myocardia of rats with doxorubicin-induced heart failure,attenuate left ventricular remodeling,and im-prove cardiac function,which is associated with the inhibition of the NF-κB-mediated upregulation of TGF-β1.

Objective To investigate the effects of WNK3 kinase on the regulation of large-conductance calcium-activated potassium channels (Maxi K channels) on African green monkey kidney fibroblast-like cells (Cos-7 cells) and its mechanisms.Methods (1) Cos-7 cells were transfected with 0,0.6,1.2,1.8 μg WNK3 plasmid+0.5 μg Maxi K plasmid.The total protein expression of Maxi K channel and the phosphorylation of mitogen-activated protein kinase (MAPK) extracellular regulated kinase-1 and-2 (ERK1/2) were detected by Western blotting.(2) Cos-7 cells were divided into the control group (2.5 μg Maxi K plasmid) and the experimental group (2.5 μg WNK3 plasmid+2.5 μg Maxi K plasmid).Cell surface biotinylation was used to investigate the cell surface protein expression of Maxi K channel in Cos-7 cells.Immunoprecipitation and Western blotting were used to detect the ubiquitination of Maxi K channel protein.(3) WNK3 kinase was knocked down by WNK3 siRNA.The lysosomal degradation pathway was blocked by the proton pump inhibitor (Baf-A1).Cos-7 cells were divided into Maxi K+negative control siRNA group,Maxi K+WNK3 siRNA group and Maxi K+WNK3 siRNA+Baf-A1 group.The protein expression of Maxi K channel protein was detected by Western blotting.Results (1) Compared with those in 0 μg WNK3 plasmid groups,in 0.6,1.2,1.8 μg WNK3 plasmid groups the total protein expression of the Maxi K channel increased and the phosphorylation level of MAPK ERK1/2 reduced on a dose-dependent manner (all P ＜ 0.01).(2)Compared with those in the control group,the total protein expression and cell surface membrane protein expression of the Maxi K channel increased in the experimental group (P ＜ 0.01),while the ubiquitination of the Maxi K channel protein reduced (P ＜ 0.01).(3) Compared with the Maxi K +negative control siRNA group,the expression of Maxi K protein reduced in the Maxi K+WNK3 siRNA group (P ＜ 0.01),but did not change in the Maxi K+WNK3 siRNA + Bar-A1 group (P ＞ 0.05).The expression of Maxi K protein in Maxi K+WNK3 siRNA+Baf-A1 group was higher than that in Maxi K+WNK3 siRNA group (P ＜ 0.01).Conclusions WNK3 kinase inhibits the lysosomal degradation pathway of Maxi K channel protein by reducing the ubiquitination of Maxi K channel,and promotes the expression of Maxi K channel protein in cells and on cell membrane.These effects may be achieved by suppressing MAPK ERK1/2 signal transduction pathway.

Objective To investigate the effects of bisoprolol on myocardial SERCA2a activity in rats with heart fail-ure.Methods Male SD rats were randomly divided into normal control group (control group), sham operation group ( sham group ) , model group , bisoprolol group ( Bis group ) , captopril group ( Cap group ) and bisoprolol plus captopril group[(Bis+Cap)group], heart failure rat model was induced by intraperitoneal injections of doxorubicin .Distilled water, bisoprolol, captopril or bisoprolol plus captopril were administrated by gastrogavage for 35 days, respectively. Indices of cardiac function and plasma levels of B-type natriuretic peptide ( BNP) were measured , myocardial expres-sion of miR-25-3p was detected by Stem-loop RT-qPCR, myocardial levels of SERCA2a and phospholamban (PLB) were detected by Western blot , myocardial SERCA2a activity was determined by the inorganic phosphorus method . Results Cardiac function in model group decreased significantly while plasma levels of BNP were significantly higher than those of control group ( P<0.01 ) .Myocardial expression of miR-25-3p in model group was significantly higher while myocardial levels of SERCA 2a and PLB,SERCA2a activity were significantly lower than those of con-trol group(P<0.01).Cardiac function in Bis group , Cap group and Bis +Cap group improved significantly while plasma levels of BNP were significantly lower than those of model group ( P<0.01 ) .Myocardial expression of miR-25-3p in Bis group, Cap group and Bis +Cap group were significantly lower while myocardial levels of SERCA2a and PLB were significantly higher than those in model group (P<0.01).The SERCA2a/PLB ratio and SERCA2a activity in Bis group and Bis +Cap group were significantly higher than those of model group ( P<0.05 ) .Conclu-sions Bisoprolol therapy improves cardiac function in rats with heart failure , which may be related to inhibition of myocardial miR-25-3p, increasing myocardial SERCA2a and PLB levels, enhancing SERCA2a activity.