AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

Background and purpose:Lobaplatin,as a traditional chemotherapeutic drug,is widely used in the treatment of malignant tumor.In recent years,its application in the field of hyperthermic intraperitoneal chemotherapy(HIPEC)has garnered increasing attention.This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer.Methods:This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital,Tongji University School of Medicine,from January 2019 to January 2023.We excluded patients who did not meet the inclusion criteria.Short-term efficacy was assessed by changes in ascitic fluid volume,and long-term survival was analyzed using the Kaplan-Meier method.The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis.Baseline characteristics and treatment outcomes were described using descriptive statistics,and the changes in CA12-5 levels before and after treatment were compared using significance tests(P＜0.01).Data entry and statistical analyses were conducted using SPSS version 26.0,and survival curves and efficacy plots were generated with GraphPad Prism(10.4.0 version).The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital(Ethics approval number:SHSY-IEC-5.0/24K134/P01).This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials(CONSORT)checklist.Results:A total of 21 patients were enrolled in this study.The median age of the patients was 61 years(ranging from 31 to 71 years).Among the 21 patients,5(23.8%)achieved complete remission(CR),5(23.8%)achieved partial remission(PR),8(38.1%)had stable disease(SD),and 3(14.3%)experienced disease progression(PD).The overall response rate(ORR)was 47.6%,and the disease control rate(DCR)was 85.7%.Survival analysis revealed a median progression-free survival(PFS)of 12.33 months and a median overall survival(OS)of 16.37 months.Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels(P＜0.01).Adverse reactions primarily included myelosuppression,hepatic and renal impairment,and nausea and vomiting,with most adverse events being mild to moderate.Conclusion:Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites,providing survival benefits and demonstrating good safety.CA12-5 may serve as a valuable predictor of poor prognosis.

Background and purpose:Lobaplatin,as a traditional chemotherapeutic drug,is widely used in the treatment of malignant tumor.In recent years,its application in the field of hyperthermic intraperitoneal chemotherapy(HIPEC)has garnered increasing attention.This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer.Methods:This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital,Tongji University School of Medicine,from January 2019 to January 2023.We excluded patients who did not meet the inclusion criteria.Short-term efficacy was assessed by changes in ascitic fluid volume,and long-term survival was analyzed using the Kaplan-Meier method.The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis.Baseline characteristics and treatment outcomes were described using descriptive statistics,and the changes in CA12-5 levels before and after treatment were compared using significance tests(P＜0.01).Data entry and statistical analyses were conducted using SPSS version 26.0,and survival curves and efficacy plots were generated with GraphPad Prism(10.4.0 version).The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital(Ethics approval number:SHSY-IEC-5.0/24K134/P01).This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials(CONSORT)checklist.Results:A total of 21 patients were enrolled in this study.The median age of the patients was 61 years(ranging from 31 to 71 years).Among the 21 patients,5(23.8%)achieved complete remission(CR),5(23.8%)achieved partial remission(PR),8(38.1%)had stable disease(SD),and 3(14.3%)experienced disease progression(PD).The overall response rate(ORR)was 47.6%,and the disease control rate(DCR)was 85.7%.Survival analysis revealed a median progression-free survival(PFS)of 12.33 months and a median overall survival(OS)of 16.37 months.Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels(P＜0.01).Adverse reactions primarily included myelosuppression,hepatic and renal impairment,and nausea and vomiting,with most adverse events being mild to moderate.Conclusion:Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites,providing survival benefits and demonstrating good safety.CA12-5 may serve as a valuable predictor of poor prognosis.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Objective:To analyze the impact of intrauterine infusion of autologous peripheral blood mononuclear cells (PBMCs) and enriched platelet plasma (PRP) on pregnancy outcomes in patients with recurrent implantation failure (RIF).Methods:A total of 96 patients with repeated implantation failures who underwent frozen embryo cycles at Hunan Provincial Maternal and Child Health Care Hospital from March 2021 to June 2023 were selected and randomly divided into a control group (19 cases), PBMCs group (31 cases), and PRP group (46 cases). The control group did not receive uterine cavity infusion treatment; Intrauterine perfusion of PBMCs in the PBMCs group; The uterine cavity of the PRP group was infused with PRP. We compared the general situation, endometrial thickness on the day of conversion, endometrial thickness on the day of transplantation, embryo implantation rate, and clinical pregnancy rate among three groups.Results:There was no statistically significant difference in age, body mass index (BMI), years of infertility, menstrual cycle, serum basal follicle stimulating hormone (FSH), basal estradiol (E 2), number of transfer cycles, number of transferred embryos, and number of high-quality embryos among the three groups (all P>0.05). There was no statistically significant difference in endometrial thickness on the conversion day among the control group, PRP group, and PBMCs group (all P>0.05). The endometrial thickness on the day of transplantation in the PRP group was greater than that in the control group and PBMCs group (all P<0.05), and there was no statistically significant difference in endometrial thickness on the day of transplantation between the control group and PBMCs group (all P>0.05). The embryo implantation rate and clinical pregnancy rate of the PRP group and PBMCs group were higher than those of the control group, and the difference was statistically significant (all P<0.05). There was no statistically significant difference in embryo implantation rate and clinical pregnancy rate between the PRP group and the PBMCs group (all P>0.05). The patients did not experience any adverse reactions such as infection, abdominal pain, or vaginal bleeding during intrauterine infusion therapy. Conclusions:Infusing autologous PBMCs or PRP into the uterine cavity before re embryo transfer in RIF patients can significantly improve embryo implantation rate and clinical pregnancy rate, and can improve assisted pregnancy outcomes; Intrauterine infusion of autologous PRP has no significant advantage over PBMCs in improving clinical pregnancy outcomes in patients with RIF; But it is more beneficial for improving the thickness of the endometrium.

Lung adenocarcinoma is a malignant tumor that is prone to distant metastasis. Common metastatic sites are brain, adrenal gland, liver, bone, and so on. Skin soft tissue metastasis is unusual, and breast metastasis is even rarer. This case is a middle-aged female patient who had experienced multi-line treatments for upper limbs, abdominal skin, and bilateral breast tissue metastases.The patient's multiple metastases were susceptible to radiation therapy.Reviewing the entire treatment process of this patient can find that the rational use of individualized comprehensive treatment methods and appropriate timing of genetic testing are very important for patients with lung adenocarcinoma to prolong their survival time and improve their quality of life.
Adenocarcinoma of Lung ; Breast Neoplasms ; Female ; Humans ; Lung Neoplasms ; Middle Aged ; Quality of Life

Objective To investigate the prevention effect and mechanism of glucocorticoid aerosol inhalation on pulmonary infection after hepatectomy. Methods Clinical data of 66 liver cirrhosis patients complicated with primary liver cancer (liver cancer) undergoing hepatectomy in the Third Afifliated Hospital of Sun Yat-sen University between January 2013 and December 2014 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. The patients were divided into the treatment group and control group according to the treatment methods. In the treatment group, 36 patients were included, 28 males and 8 females, aged from 21 to 66 years with a median age of 43 years. All patients were given with aerosol inhalation of 1 mg of budesonide (pulmicort)+30 mg of ambroxol (mucosolvan), twice daily for consecutive 6 d. In the control group, 30 patients were included, 18 males and 12 females, aged ranging from 23 to 67 years with a median age of 48 years. All cases were given with aerosol inhalation of 30 mg of ambroxol (mucosolvan), twice daily for consecutive 6 d. The changes of the arterial blood gas analysis results and X-ray radiography were observed between two groups. Arterial blood gas analysis results of two groups were compared using t test and the ratio was compared using Chi-square test. Results After aerosol inhalation, partial pressure of oxygen (PaO2) and oxygenation index (OI) in the treatment group were (116±15) and (590±42) mmHg (1 mmHg=0.133 kPa), signiifcantly higher compared with (85±17) and (452±54) mmHg before treatment( t=2. 4 2 6 , 2. 5 3 3;P<0.05). In the control group, PaO2 and OI were (101±16) and (535±50) mmHg after aerosol inhalation, signiifcantly higher compared with (86±16) and (460±56) mmHg before treatment (t=3.401, 2.440;P<0.05). In the treatment group, alveolar-arterial oxygen difference (A-aDO2) was (65±18) mmHg, significantly lower than (96±22) mmHg before treatment (t=-3.578, P<0.05). After aerosol inhalation, signiifcant differences were observed in PaO2 and A-aDO2 between the treatment group and control group (t=3.925, -6.355; P<0.05). In the treatment group, the postoperative incidence of pulmonary infection was 6%(2/36), significantly lower compared with 13%(4/30) in the control group (χ2=15.240, P<0.05). Conclusion Inhalation of glucocorticoid aerosol effectively prevents the incidence of pulmonary infection after hepatectomy probably through enhancing PaO2, improving oxygenation status of tissues and organs and increasing pulmonary ventilation function.

OBJECTIVE: To investigate the influence of allergic rhinitis on negative emotion. METHOD: One hundred and ninety cases with allergic rhinitis as observer group were investigated by state-trait anxiety inventory (STAI) and self-rating depressive scale (SDS). According to pathogenetic condition, patients were divided into persistent allergic rhinitis 71 cases (A group) and intermittent allergic rhinitis 119 cases (B group). Meanwhile, 190 healthy persons as control group were compared with observer group. RESULT: (1) The main allergens of allergic rhinitis were dermatophagoides pteronyssinus, dermatophagoides farina, pollen, and epiphyte, which the skin index was above "++" by skin prick test. (2) The state anxiety score of observer group (42.17±16.21) was significantly higher than control group (38.78±16.54), t=2.02, P<0.05. There were no difference in trait anxiety between observer group and control group (41.25±16.16 vs. 41.19±16.84), P>0.05. The anxiety scores of female in A and B groups were higher than that of female in control group (43.77±15.76, 42.93±15.58 vs 38.44±15.71), P<0.05. (3) The score of SDS in A and B group was significantly higher than that of control group (37.78±9.22, 39.65±9.87 vs 35.24±7.81), P<0.01. The rate of depression in observer group (11.6%, 22/190) was significantly higher than that of control group (2.6%, 5/190), Χ2=11.52, P<0.01. CONCLUSION The allergic rhinitis may cause patients anxiety and depression, especially for female, but patients with allergic rhinitis have no significant trait anxiety.
Allergens ; Animals ; Anxiety ; complications ; Case-Control Studies ; Depression ; complications ; Female ; Humans ; Male ; Personality Inventory ; Phenotype ; Pyroglyphidae ; Rhinitis, Allergic ; psychology ; Skin Tests

OBJECTIVE: To investigate the influence of nasal septal deviation on the incidence of bilateral sinusitis. METHOD: Two thousand and seventy-four cases of nasal septal deviation with chronic sinusitis available from January 2006 to March 2012 were reviewed retrospectively. RESULT: Of these 2074 cases, 1 687 (81.3%) patients had sinusitis in narrow side and 1582 (76.3%) in wide side, the difference was statistically significant (P < 0.01) and the relative risk value in narrow side (1.4) was higher than wide side (0.7) associated with the incidence of sinusitis. There was significant difference (P < 0.05) between the two group counting datas analyzed by rank sum test, and the mean rank order in narrow side was 1656.396, significantly greater than wide side (1 612.184). The incidence of sinusitis in men was 50.6% (1049/2074), in women was 49.4% (1025/2074), and there was no significant difference between them. Deviating leftward was 1148 cases (55.4%), deviating rightward was 926 cases (44.6%), and the difference was statistically significant (P < 0.05). Anatomic variations in narrow side and wide side were uncinate process hypertrophy (7.0%, 27.0%), middle turbinate hypertrophy (7.8%,38.0%), ethmoidal bulla hypertrophy (26.2%, 39.0%), paradoxical middle turbinate (5.4%, 15.5%), hypertrophic inferior turbinate (52.9%, 67.0%) and mucosa pachynsis (0.5%, 2.8%), respectively. CONCLUSION Sinusitis incidence in narrow side is higher than wide side. There is no significant difference between the incidence of sinusitis in men and women. The majority of nasal septum deviate leftward. Higher incidence of sinusitis in wide side is the result of compensatory mechanism. Only septoplasty may not restore the normal venting function in nasal cavity. Hypertrophic inferior turbinate are closely correlated with sinusitis.
Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Nasal Cavity ; Nasal Septum ; abnormalities ; Paranasal Sinuses ; Retrospective Studies ; Sinusitis ; epidemiology ; Turbinates ; abnormalities ; Young Adult