[Clinical application of a novel separated magnetic controlled forceps assisted single-incision laparoscopic cholecystectomy].

Objective: To explore the application value of a novel separated magnetic-controlled forceps in transumbilical single-incision laparoscopic cholecystectomy (SILC). Methods: This is a prospective case series study. Data from patients who underwent SILC at the Department of General Surgery, the Second Affiliated Hospital of Air Force Medical University from March to August 2023 were prospectively collected, based on inclusion and exclusion criteria. All patients underwent cholecystectomy assisted by a novel separated magnetic-controlled forceps. Surgical time, intraoperative blood loss, the need for additional incisions during surgery, and the length of hospital stay were recorded to assess surgical difficulty and effectiveness. Postoperative pain scores and complications were documented to evaluate the safety of the procedure. The collaboration experience of the surgeon and assistant was evaluated using a 5-point Likert scale to assess the feasibility of this surgical approach. Informed consent was obtained from all patients in accordance with medical ethical regulations. Patients were followed up through outpatient visits or telephone calls, with follow-up at 7 days and 1 month after surgery, and evaluation of incisional scar healing and completion of satisfaction questionnaires. Follow-up was conducted until September 30, 2023. Results: A total of 45 patients were included in the study,including 19 males and 26 females,aged (42.7±4.2)years(range:32 to 61 years). The difficulty of the operation was evaluated as grade 1 or 2 in 38 cases(84.4%) and grade 3 in 7 cases(15.6%). Operation time was (37.3±5.3) minutes(range: 25 to 80 minutes),and intraoperative blood loss(M(IQR)) was 17.8(35.0) ml (range:10 to 60 ml). All surgical procedures proceeded smoothly without intraoperative incidents, and the overall satisfaction of the surgeon and assistants was high. All patients underwent successful day surgery management and were discharged within 48 hours of hospitalization. The postoperative pain scores at 1, 7, and 30 days were 3 (4), 1 (3), and 0 (2), respectively. The follow-up time was 5.0(2.2) weeks (range: 3 to 7 weeks), with no occurrence of grade 3 to 4 adverse reactions, and the patients were satisfied with the cosmetic effect of the umbilical incision. Conclusions: The novel separated magnetic-controlled forceps can be applied in transumbilical SILC. It has the advantages of convenient operation, and patients are satisfied with the surgical results.

[Efficacy of intravenous thrombolysis with tenecteplase in treating the branch atheromatous disease].

Objective: To explore the efficacy of intravenous thrombolysis with tenecteplase (TNK) in the treatment of branch atheromatous disease (BAD). Methods: A total of 148 BAD patients hospitalized in the stroke center of Zhengzhou People's Hospital from January 2020 to March 2023 were retrospectively included. According to whether TNK was used for treatment, the patients were divided into the TNK group (52 cases) and the control group (96 cases). The propensity score matching (PSM) method was used to eliminate baseline differences between the two groups, and 46 pairs were successfully matched. Early neurological deterioration (END) was defined as an increase in the national Institutes of Health Stroke Scale (NIHSS) scores within 7 days of stroke≥2. The 90-day modified Rankin Scale (mRS) was used to compare the long-term efficacy between the two groups. A binary logistic regression model was used to analyze the influencing factors of clinical outcomes in patients with BAD. Results: Among the 92 patients, 62 were males and 30 were females, with an average age of (61.0±9.5) years. After PSM, there were statistically significant differences in NIHSS score at discharge [2 (0, 4) vs 4 (3, 8)] and length of hospital stay [9 (6, 13) d vs 11 (9, 14) d] (both P<0.05) between the two groups. The proportion of mRS 0-2 in TNK group was higher than that in the control group [82.6%(38/46) vs 60.8%(28/46)], while the proportion of END and mRS≥4 was lower than that in the control group [10.8%(5/46) vs 30.4%(14/46); 8.7%(4/46) vs 26.0%(12/46)], with statistically significant differences (P<0.05). The 90-day mortality in the control group was 2.2% (1/46), while no death was detected in the TNK group. Conclusion: Intravenous thrombolysis therapy with TNK can not only increase the proportion of 90-day mRS 0-2 in BAD patients, but also reduce the incidence of END.

[Effect of PCSK9 inhibitors on early neurological deterioration in patients with branch atheromatous disease].

Objective: To investigate the effect of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors on the incidence of early neurological deterioration during the treatment of branch atheromatous disease (BAD). Methods: A retrospective analysis of 297 BAD patients admitted to the Department of Neurology in Zhengzhou People's Hospital from January 2020 to April 2023 was made. According to whether to use PCSK9 inhibitor treatment, they were divided into PCSK9 inhibitor group (81 cases) and control group (216 cases). Propensity score matching (PSM) method was used to eliminate the general situation difference between PCSK9 inhibitor group and control group. Seventy-two cases were successfully matched in each group. The early neurological deterioration (END) and low-density lipoprotein cholesterol (LDL-C) were compared. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase≥2 points within 72 hours after stroke. Suspicious influencing factors leading to END were screened for multivariate logistic regression model analysis. Results: After PSM matching, among the 144 patients, 90 were male and 54 were female, aged (61.2±9.6) years. After matching, The hospital stay[M(Q1, Q3)] [9(7, 11)d vs 10(8, 13)d] in PCSK9 and NIHSS score at discharge [2(1, 3) vs 3(1, 4) points] were significantly different from those in the control group (all P<0.05). In addition, the incidence of END was reduced in the PCSK9 inhibitor group [12.5%(9/72) vs 31.9%(23/72),P<0.05]. Multivariate logistic regression analysis found that C-reactive protein (CRP)(OR=1.119,95%CI: 1.010-1.240, P<0.05) and PCSK9 inhibitor (OR=0.298, 95%CI: 0.117-0.755, P<0.05) were factors associated with the development of END. Conclusion: The use of PCSK9 inhibitors in the treatment of patients with BAD can reduce the incidence of END.

[Characteristics and regulatory mechanisms of lipid metabolism remodeling after malignant transformation of glioma-associated macrophages].

Objective: To observe the lipid metabolism characteristics of tumor-associated macrophages (TAM) after malignant transformation in the glioma micro-environment, and analyze the biological phenotype changes and regulatory mechanisms after inhibiting the lipid metabolism remodeling. Methods: Twelve male Balb/c mice of 6-8 weeks were used in the study. Macrophages (Mφ) were derived from mouse bone marrow, and malignantly transformed macrophages (tMφ1 and tMφ2) were cloned from the model of glioma stem cell (GSC) through interaction with Mφ in vivo and in vitro. Intracellular lipid droplet formation and cellular cholesterol content were measured respectively in Mφ, tMφ1 and tMφ2. qRT-PCR was performed to detect the genes expression level related with lipid metabolism, including sterol regulatory element binding protein (SREBP), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase (HMG-CoA). Simvastatin (SIM) was used to analyze the proliferation, immigration and invasiveness ability in tMφ1 and tMφ2 after inhibition of the lipid metabolism. Differential expression profiles of miRNAs after SIM treatment were constructed in t-Mφ1 and bio-informatics analysis was screened and verified for miR449a and its target gene sorting micro-tubule connectin 17 (SNX17) associated with lipid metabolism remodeling. The effect on SNX17 by up-regulated miR-449a were analyzed by qRT-PCR and Western blot, meanwhile, the biological phenotype and cholesterol content were observed after up-regulation of miR449a. Low-density lipoprotein receptor (LDLR) protein levels after SNX17 knockdown and intracellular cholesterol content after LDLR knockdown were detected respectively. Results: The numbers of intracellular lipid droplet formation in tMφ1 and tMφ2 were more than that in Mφ (P<0.001). Likewise, the relative contents of cholesterol (3.89±0.68 and 3.56±0.53), SREBP (4.78±0.60 and 2.84±0.41), FASN (4.65±0.70 and 3.01±0.45), and HMG-CoA (5.74±0.55 and 2.97±0.34) were significantly higher in tMφ1 and tMφ2 than those of Mφ (1.01 wel, 1.02 wel and 0.99 wel, respectively) (all P<0.001). The proliferation rates of tMφ1 and tMφ2 decreased from (47.06±5.88) % and (45.29±5.64)% to (23.53±4.70)% and (18.74±5.76)%, respectively after treatment with SIM (both P<0.05). The numbers of migrated cells decreased from 1 025±138 and 350±47 to 205±63 and 99±25, respectively (both P<0.001). And the numbers of invasiveness cells decreased from 919±45 and 527±34 to 220±23 and 114±21, respectively (both P<0.001). While the relative intracellular cholesterol content decreased to 0.52±0.08 and 0.58±0.07 (both P<0.05), respectively. MiR-449a was screened from tMφ1 by SIM, and the target gene was analyzed and verified to be SNX17. SNX17 expression was down-regulated, and the proliferation rate, the number of migration and invasiveness was significantly decreased after miR-449a over-expression (all P<0.05). Low-density lipoprotein receptor (LDLR) expression was down-regulated after knock-down of SNX17, while the cholesterol content was decreased after knock-down of LDLR in tMφ1 and tMφ2 (all P<0.05). Conclusions: Malignantly transformed TAMs undergo lipid metabolism remodeling characterized with enhanced lipid metabolism. MiR-449a regulates the LDLR by targeting SNX17, thereby affecting the lipid metabolism of malignantly transformed macrophages, and subsequently inhibiting its proliferation, migration, and invasion ability. Precise intervention with miR-449a/SNX17/LDLR axis could provide an experimental basis for reversing its tumor-promoting micro-environment remodeled by GSC through metabolic intervention.

[Analysis of FBN1 genemutations in a pedigree with Marfan syndrome].

Mutations in fibrillin-1 (FBN1) were detected in an autosomal dominant Marfan syndrome (MFS) pedigree. The related phenotypes and the significance of mutation screening were discussed. Complete medical and cardiovascular examinations for all pedigree members were performed. Whole exons sequencing (WES) was used to sequence the DNA of the patients and their relatives. The potential pathogenic mutation sites were screened by bioinformatics method. Sanger sequencing was used to verify the mutation sites in the pedigree. The results showed that FBN1 missense mutation was c.6806 T>C in exon 56, resulting in isoleucine being replaced by threonine (p. Ile2269Thr). This mutation has not been reported in Chinese Han population. The occurrence of the mutations strongly correlated with the phenotypes of the patients. The results expand the mutation spectrum of FBN1, and it is helpful to further explore the molecular pathogenesis of MFS and MFS related diseases.

[Progress of regulatory T cells in the regulation of anti-tuberculosis immunity].

Mycobacterium tuberculosis (MTB), as an intracellular parasitic bacterium, invades the human body mainly through droplets, which can lead to multiple organ infection, causing the body to produce T cell-dominated immunity to tuberculosis (TB). Regulatory T cells (Tregs), as a class of T lymphocyte subsets that negatively regulate the immune response of the body, play an important role in regulating immune balance in host anti-tuberculosis immunity. A large number of studies have shown that MTB-specific Tregs affects the occurrence and development of tuberculosis and the efficacy of the vaccine. Therefore, elucidating the role and regulatory mechanism underlying anti-MTB immune response of MTB-specific Tregs will help to further understanding of the decrease of host anti-MTB immune cell function, and provide a basis for the study of immunotherapy of TB. This paper briefly introduces the subtypes and functions of Tregs, and systematically reviews the research progress of Tregs in many fields of TB.

[Neck musculoskeletal disorders and their influence factors among welders in an automobile factory].

Objective: To explore the prevalence and risk factors of neck musculoskeletal diseases (MSDs) of welders among an automobile factory. Methods: In June 2019, a cluster random sampling method was used to select 677 electric welders from an automobile manufacturing plant in Shiyan City as the survey objects, and a questionnaire survey was conducted using the "Musculoskeletal Disorders Questionnaire" to analyze the prevalence and influencing factors of neck MSDs, and used logistic regression to analyze the relationship between the influencing factors and the prevalence of cervical MSDs. Results: The prevalence rate of MSDs in neck of welders was 54.8% (371/677) . The exposure rate of occupational factors, from high to low, were neckin a bent formord porsure was 71.6% (486/677) , repetitive head movements was 55.1% (373/677) , working in uncomfortable postures was 48.7% (330/677) and neck twisted was 46.8% (317/677) respectively. Sex, age, educational level, length of service, smoking, neck tilt, neck twist, working in uncomfortable posture and head repetitive movements were the risk factors of neck MSDs (P<0.05) . Multiple logistic regression analysis showed that, the main influencing factors of neck MSDs were sex, education level, age, length of service, smoking, neck tilt, working in uncomfortable posture (OR = 2.11, 2.03, 1.83, 1.21, 1.78, 1.90, 1.58, 95%CI: 1.28~3.48、1.47~2.81、1.33~2.52、1.03~1.41、1.22~2.60、1.28~2.83、1.11~2.27, P<0.05) , rest had protective effect on neck MSDs (OR= 0.38, 95%CI: 0.17~0.88, P<0.05) . Conclusion: Welders in automobile factory was highly exposed to occupational risk factors for neck MSDs. Occupational risk factors such as neck in a bent forward posture, working in an uncomfortable posture, prolonged siting, repetitive head movement should be the focus of intervention.

[Characteristics of single subcortical small infarction in the middle cerebral artery territory].

Objective: To investigate the characteristics and possible mechanisms of differtent stroke patterns of single subcortical small infarction (SSSI) in the middle cerebral artery (MCA) territory. Methods: The clinical and imaging data of patients with acute SSSI in MCA territory admitted to the Neurology Department of People's Hospital of Zhengzhou City from January 2016 to December 2017 were retrospectively analyzed. According to the presence of MCA stenosis and whether the lesion sites on axial DWI-MRI involved the lowest basal ganglia, SSSl were divided into different patterns. The clinical and imaging characteristics of patients with different stroke patterns were compared. Results: Of the 91 patients, 24 (26.37%) were SSSI with parental artery disease (SSSIPAD), 28 (30.77%) were proximal SSSI without PAD (pSSSI-PAD) and 39 (42.86%) were distal SSSI without PAD (dSSSI-PAD). There were significant differences in age, hypertension, diabetes mellitus, smoking, NIHSS score, low density lipoprotein cholesterin (LDL-C) level, infarct layers ≥3, lesion diameter, white matter hyperintensity, lacunar infarction, enlarged perivascular space, cerebral microbleed, concomitant intracranial and extracranial atherosclerotic stenosis among the three groups (all P<0.05). Compared with SSSIPAD(-), patients with SSSIPAD(+) had significantly higher prevalence of smoking, proximal SSSI, ICAS, ECAS, NIHSS score, LDL-C level and larger lesion diameter (all P<0.05). Conclusions: The clinical characteristics and imaging features were different among different SSSI stroke patterns. SSSIPAD is an important infarct type. pSSSI-PAD may showed intermediate features of SSSIPAD and dSSSI-PAD, and evidence of atherosclerosis should be carefully searched for such patients.

[Clinical significance of targeting drug-based molecular biomarkers expression in ovarian clear cell carcinoma].

Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues. Results: The positive rates of EGFR, HER2, AURKA,BRCA1, BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20% (8/40) vs 30% (7/23) , 22% (9/40) vs 35% (8/23) , 38% (15/40) vs 35% (8/23) , 42% (17/40) vs 39% (9/23) , 20% (8/40) vs 22% (5/23) , 25% (10/40) vs 17% (4/23) , and there were no significant differences between primary and recurrent OCCC (all P>0.05). χ(2)-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance (P<0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all P>0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC (4 months vs 10 months, log-rank test, P<0.05 for HER2; and 4 months vs 10 months, P<0.05 for AURKA); and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, P<0.05 for HER2; and 13 months vs 43 months, P<0.05 for AURKA). However, multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC (P>0.05). Conclusion: HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.

[Etiological analysis and establishment of a discriminant model for lower respiratory tract infections in hospitalized patients].

Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the dependent variable. The total positive predictive value was 64.7%(77/119), with 66.7% for bacterial infection, 78.0% for viral infection and 33.3% for the mixed infection. Conclusions: The mostly detected pathogens were Pseudomonas aeruginosa, atypitcal pathogens, Klebsiella pneumoniae, influenza A virus and human cytomegalovirus in hospitalized patients with LRTI in this hospital. The discriminant diagnostic model established by clinical features may contribute to predict the pathogens of LRTI.

[Role of farnesoid X receptor in rats with acute cholestatic hepatitis].

OBJECTIVE: To investigate the role of farnesoid X receptor (FXR) and its downstream molecules small heterodimer partner (SHP), UDP-glucuronosyltransferase 2B4 (UGT2B4), and bile salt export pump (BSEP) in rats with acute cholestatic hepatitis. METHODS: A total of 20 Sprague-Dawley rats were randomly divided into normal control group and model group, with 10 rats in each group. The rats in the model group were given a single dose (50 mg/kg) ofα-naphthyl isothiocyanate by gavage to establish the animal model of acute cholestatic hepatitis. Quantitative real-time PCR was used to measure the mRNA expression of FXR, UGT2B4, and BSEP in liver tissue at 48 hours after gavage. An automatic biochemical analyzer was used to measure the serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, total bile acid, aspartate aminotransferase, alkaline phosphatase, andγ-glutamyl transferase. The independent samples t-test was used for comparison of means between groups. RESULTS: The model group had significantly lower mRNA expression of FXR, SHP, UGT2B4, and BSEP in liver tissue than the normal control group (0.152±0.088/0.559±0.194/0.177±0.039/0.561±0.123 vs 1.137±0.215/1.512±0.309/2.394±0.462/1.631±0.376, t = 13.408, 8.260, 15.121, and 8.553, all P < 0.05). The model group had significantly higher liver function parameters than the normal control group (all P < 0.01). CONCLUSION: FXR, SHP, UGT2B4, and BSEP are involved in the development of acute cholestatic hepatitis. Reduced expression of FXR may cause reduced expression of downstream SHP, UGT2B4, and BSEP, increase the synthesis of bile acid, weaken detoxicating and transporting functions, and thus mediate the development of cholestatic hepatitis.

[Establishment and evaluation of a prognostic model for acute pulmonary embolism].

OBJECTIVE: To identify the factors influencing the prognosis of patients with acute pulmonary embolism(PE) and to establish a prognostic model. METHODS: The clinical data of 331 patients (141 males and 190 females, aged 9 to 87 years ) with acute PE in Fujian Hospital from January 2007 to September 2013 were analyzed. Univariate analysis and logistic regression analysis were used for selecting the independent prognostic factors for acute PE. Based on logistic regression analysis, a prognostic model for PE was established. RESULTS: Univariate analysis showed that statistically significant (all P<0.05) factors influencing the prognosis of PE were diabetes, tricuspid systolic murmur, body temperature, respiratory rate, heart rate, aspartate aminotransferase, triglycerides, abnormal ECG, mechanical ventilation, circulatory failure during hospitalization, risk stratification of PE, types of treatment, and use of low-molecular-weight heparin and Warfarin. Logistic regression analysis showed that recent (<1 month) operation or fracture, tricuspid systolic murmur, high triglyceride level, circulatory failure during hospitalization and mechanical ventilation were independent factors for poor prognosis of PE, while combined use of low-molecular-weight heparin and Warfarin was a protective factor for the prognosis of PE. The Fisher prognostic model equation was y=0.144+ 1.266x1+ 0.869x2+ 1.794x3-0.517x4+ 3.555x5+ 0.661x6. The accuracy of the Fisher discriminant function was 93.0%. CONCLUSION: Recent (<1 month) operation or fracture, tricuspid systolic murmur, high triglyceride level, shock during hospitalization and mechanical ventilation were signs of poor prognosis for PE, while combined use of low-molecular-weight heparin and Warfarin were beneficial for the prognosis. The discriminant function based on these data can be helpful for predicting the prognosis of patients with PE.

Testing the mutant selection window hypothesis in vitro and in vivo with Staphylococcus aureus exposed to fosfomycin.

The purpose of this study was to test the mutant selection window (MSW) hypothesis in vitro and in vivo with Staphylococcus aureus exposed to fosfomycin. With the in vitro time-kill studies, S. aureus ATCC 29213 [with a minimal concentration that inhibits colony formation by 99% (MIC99) of 2.2 µg/mL and a mutant prevention concentration (MPC) of 57.6 µg/mL] lost fosfomycin susceptibility at antibiotic concentrations (2×, 4×, and 8× MIC) that are between the lower and upper boundaries of the MSW. In the tissue-cage model, S. aureus was exposed to fosfomycin pharmacokinetics at concentrations below the MIC99, between the MIC99 and the MPC, and above the MPC, respectively. Changes in susceptibility and counts of total and resistant viable bacteria were monitored in tissue-cage fluid obtained daily. However, the selection of resistant mutants was not observed during antibacterial treatment and 48 h after the termination of fosfomycin treatment, regardless of the fosfomycin dosage. Besides, we found no differences between the in vitro-isolated mutant and its sensitive parental strain, which indicates the absence of fitness cost of fosfomycin resistance in S. aureus ATCC 29213. These findings demonstrate that agar plate determinations do not fit the MSW for fosfomycin treatment of rabbits infected with S. aureus ATCC 29213; therefore, the existence of the window must be demonstrated not only in vitro but also in vivo. Further research is needed on the exact mechanism of resistance.

WY14643 combined with all-trans retinoic acid acts via p38 MAPK to induce "browning" of white adipocytes in mice.

The ability of mammals to resist body fat accumulation is linked to their ability to expand the number of "brown adipocytes" within white fat depots. All-trans retinoic acid (t-RA) and peroxi-some proliferator-activated receptor-α (PPARα) have been implicated in "browning-like" or "browning" programs, respectively. However, a PPARα-agonist (WY14643) failed to regulate the expression of the uncoupling protein 1(UCP1) gene unless combined with retinoic acid. This study investigated the effects of the PPARα-agonist WY14643 combined with t-RA, on the "browning" of white adipocytes in mice mediated by UCP1, and the molecular mechanisms involved in this process. We compared the effects of WY14643 alone and WY14643 combined with t-RA or the p38 MAPK-inhibitor, SB203580, on white adipocytes after 24 h using the expression of UCP1, detected with RT-PCR and western blot. We also determined the mechanism by which p38 MAPK and phospho-p38 MAPK influence the process of "brown-ing" using western blot. All concentrations of WY14643 failed to in-duce UCP1 mRNA expression, protein expression, or phosphorylation of p38 MAPK (P < 0.05). WY14643 combined with t-RA was observed to induce UCP1 mRNA expression, protein expression, and phosphory-lation of p38 MAPK (P < 0.05). SB203580 combined with WY14643 and t-RA suppressed UCP1 mRNA expression, protein expression, and p38 MAPK phosphorylation (P < 0.05). WY14643 combined with t-RA can induce the transformation of white adipocytes to brown adipocytes through activation of the p38 MAPK signaling pathway.

Activity of corilagin on post-parasiticide liver fibrosis in Schistosomiasis animal model.

This study investigates the effects and possible molecular mechanisms of corilagin extraction on prevention of Schistosoma japonicum ova-induced granulomas and liver fibrosis. As a result, under a light microscope, when compared to a model group, the corilagin group showed smaller granulomas, less liver cell denaturation and less inflammatory cell infiltration, and the connective tissues were significantly decreased. By Masson staining, the liver sections from the corilagin group showed less collagen distributed around granulomas, decreased liver fibrosis in the portal tracts and less formed interlobular tissue. The expression of hydroxyproline, IL-13 in liver and GATA3 in spleen in the model group was significantly higher than that in the normal group (P less than 0.05 or 0.01), while the level of hydroxyproline, IL-13 and GATA3 in the corilagin group were significantly lower than that in the model group (P less than 0.05). In conclusion, corilagin extraction can decrease the level of Th2-associated profibrotic cytokine IL-13, and down-regulate the transcription of GATA3 mRNA in spleen cells, which alleviate the hepatic fibrosis caused by egg granuloma in Schistosoma japonicum infection.

[Clinical presentation and prognosis in children over 10-year-old with primary nephrotic syndrome].

Objective: To summary the clinical presentation and prognosis of primary nephrotic syndrome (PNS) in teenagers. Methods: The clinical data, renal pathological types and prognosis of 118 children over 10-year-old with PNS treated in the Department of Nephrology of the Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to December 2020 were retrospectively analyzed, with 408 children ≤10-year-old as control group synchronously. Chi-square test was used to compare the difference of clinical types, pathologic types, response to steroids and tubulointerstitial changes between the groups. The teenagers with steroid resistant nephrotic syndrome (SRNS) were divided into initial non-responder group and late non-responder group. Kaplan-Meier method was used to compare the difference of persistent proteinuria, and Fisher's exact test for the histological types. Results: There were 118 children >10-year-old, including 74 males and 44 females, with the onset age of 12.1 (10.8, 13.4) years; and 408 children ≤10-year-old with the onset age of 4.5 (3.2, 6.8) years. The proportion of SRNS was significantly higher in patients >10-year-old than those ≤10-year-old (24.6% (29/118) vs. 15.9% (65/408), χ2=4.66, P=0.031). There was no statistical difference in the pathological types between >10-year-old and ≤10-year-old (P>0.05), with minimal change disease the most common type (56.0% (14/25) vs. 60.5% (26/43)). The percentage of cases with renal tubulointerstitial lesions was significantly higher in children >10-year-old compared to those ≤10-year-old (60.0% (15/25) vs. 23.3% (10/43), χ2=9.18, P=0.002). There were 29 cases presented with SRNS in PNS over 10-year-old, including 19 initial non-responders and 10 late non-responders. Analyzed by Kaplan-Meier curve, it was shown that the percentage of persistent proteinuria after 6 months of immunosuppressive treatments was significantly higher in initial non-responders than those of the late non-responders ((22±10)% vs. 0, χ2=14.68, P<0.001); the percentage of minimal change disease was significantly higher in patients of late non-responders than those of the initial non-responders (5/6 vs. 3/13, P=0.041). Of the 63 >10-year-old with steroid-sensitive nephrotic syndrome followed up more than one year, 38 cases (60.3%) had relapse, and 14 cases (22.2%) were frequent relapse nephrotic syndrome and steroid dependent nephrotic syndrome. Among the 45 patients followed up over 18-year-old, 22 cases (48.9%) had recurrent proteinuria continued to adulthood, 3 cases of SRNS progressed to kidney insufficiency, and one of them developed into end stage kidney disease and was administrated with hemodialysis. Conclusions: Cases over 10-year-old with PNS tend to present with SRNS and renal tubulointerstitial lesions. They have a favorable prognosis, but are liable to relapse in adulthood.

Morphology of the developing muscularis externa in the mouse esophagus.

Muscularis externa of mouse esophagus is composed of two skeletal muscle layers in the adult. But less attention is paid to the histogenesis of the muscularis externa of the esophagus, and controversies still exist about the developmental process and the spatio-temporal expression characteristics of muscle-specific proteins during the development of esophageal muscularis externa. To further probe into the developmental pattern of muscularis externa of the mouse esophagus and the expression characteristics of different muscle-specific proteins, immunohistochemical and terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick-end labeling apoptotic staining methods are used to investigate the expression patterns of different muscle-specific proteins and to elucidate the relationship of these protein expressions with the development of muscularis externa of the mouse esophagus. Thus, an understanding of the developing esophageal muscularis externa may be important for developing therapeutic strategies for the treatment of human esophagus diseases. Serial sections of mouse embryos from embryonic day (ED) 12 to ED18, and full-length esophagi from postnatal first to 5th day were stained with monoclonal antibodies against α-smooth muscle actin (α-SMA), α-sarcomerical actin (α-SCA), desmin, and monoclonal anti-skeletal myosin (MHC), while apoptosis was determined using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling assay. The expression of α-SMA was started at ED12. During the development of ED14-ED15, α-SMA positive cells were seen extending from the walls of left three, four, and six arch arteries toward the dorsal wall of esophagus. Stronger expression of α-SCA and desmin could be detected at ED14 and ED15, expression intensity in caudal segment and inner layer was stained stronger than that of cranial segment and outer layer, but after ED16, strong expression of α-SCA and desmin was found in the outer layer of muscularis externa. Expression of MHC was first detected in the outer layer of cranial segment of muscularis externa at ED17. At ED18, MHC had extended to the level of thyroid gland, staining intensity in the outer layer and cranial segment was stronger than that of inner layer and caudal segment. One to five days after birth, the thickness of the esophageal muscle layer was obviously increased. Most of the muscle cells in the cranial segment of esophagus showed strong expression of α-SCA and clear cross striations at higher magnification. With progression toward the caudal segment, expression intensity of α-SCA became weaker, but the expression intensity of desmin was the same at different levels of esophagus. The muscle fibers were arranged densely with high expression of MHC in the cranial segment. During the development of esophageal muscularis externa, few apoptotic cells were observed. α-SMA, α-SCA, desmin, and MHC show different expression patterns. The differentiation of outer layer of esophageal muscularis externa is quicker than that of inner layer, and the caudal segment is quicker than that of the cranial segment. Besides, apoptosis may not participate in the development of esophageal muscularis externa. The smooth muscle cells from arch arteries may participate in the development of esophageal muscularis externa.

Toll-like receptor 2 type 1 and type 2 polymorphisms in different chicken breeds.

Toll-like receptors mediate immune responses via recognition of pathogen-associated molecular patterns. Polymorphisms of toll-like receptors may affect their recognition of pathogen-associated molecular patterns, leading to varied host resistance to pathogenic infections. However, little is known about the polymorphisms of chicken toll-like receptors (ChTLR) among breeds. In this study, we cloned ChTLR2 type 1 and type 2 genes from 7 chicken breeds and analyzed their sequences. It was found that there were 10 amino acid polymorphism sites in ChTLR2 type 1 and type 2, among which 6 sites were in type 1 (5 sites in the extracellular domain and 1 site in the cytoplasmic domain) and 4 sites were in type 2 (all 4 sites in the extracellular domain). These results demonstrate that ChTLR2 type 1 and type 2 genes are polymorphic among chicken breeds, suggesting a varied resistance among breeds of chicken. We found that Laiwu Black chicken breeds have distinctive polymorphic sites at I699T in the type 1 and H561R in the type 2 ChTLR2 gene. Beijing Fatty chickens have distinctive sites at Q45R in type 1 and V66L in type 2. Nongda No.3 Chickens have distinctive sites at L115P, H232Y, and T494A in type 1. Hy-Line variety brown chickens have distinctive sites at I311V in type 2. Beijing White 939 chickens have distinctive sites at E284G in type 1 and A22V in type 2. These findings may provide some clues toward understanding the resistance of lighter chickens to salmonellosis.

Poly(acrylic acid) modifying bentonite with in-situ polymerization for removing lead ions.

In this paper, a new kind of poly(acrylic acid) modified clay adsorbent, the poly(acrylic acid)/bentonite composite (PAA/HB) was prepared by in-situ polymerization, and utilized to remove lead(II) ions from solutions. The maximum adsorption of adsorbent is at pH 5 for metal ions, whereas the adsorption starts at pH 2. The effects of contact time (5-60 min), initial concentration of metal ions (200-1,000 mg/L) and adsorbent dosage (0.04-0.12 g/100 mL) have been reported in this article. The experimental data were investigated by means of kinetic and equilibrium adsorption isotherms. The kinetic data were analyzed by the pseudo-first-order and pseudo-second-order equation. The experimental data fitted the pseudo-second-order kinetic model very well. Langmuir and Freundlich isotherms were tried for the system to better understand the adsorption isotherm process. The maximal adsorption capacity of the lead(II) ions on the PAA/HB, as calculated from the Langmuir model, was 769.2 mg/g. The results in this study indicated that PAA/HB was an attractive candidate for removing lead(II) (99%).