Ubiquitin protein E3 ligase ASB9 suppresses proliferation and promotes apoptosis in human spermatogonial stem cell line by inducing HIF1AN degradation

Background Spermatogonial stem cells (SSCs) are critical for sustaining spermatogenesis. Even though several regulators of SSC have been identified in rodents, the regulatory mechanism of SSC in humans has yet to be discovered. Methods To explore the regulatory mechanisms of human SSCs, we analyzed publicly available human testicular single-cell sequencing data and found that Ankyrin repeat and SOCS box protein 9 (ASB9) is highly expressed in SSCs. We examined the expression localization of ASB9 using immunohistochemistry and overexpressed ASB9 in human SSC lines to explore its role in SSC proliferation and apoptosis. Meanwhile, we used immunoprecipitation to find the target protein of ASB9 and verified its functions. In addition, we examined the changes in the distribution of ASB9 in non-obstructive azoospermia (NOA) patients using Western blot and immunofluorescence. Results The results of uniform manifold approximation and projection (UMAP) clustering and pseudotime analysis showed that ASB9 was highly expressed in SSCs, and its expression gradually increased during development. The immunohistochemical and dual-color immunofluorescence results displayed that ASB9 was mainly expressed in nonproliferating SSCs. Overexpression of ASB9 in the SSC line revealed significant inhibition of cell proliferation and increased apoptosis. We predicted the target proteins of ASB9 and verified that hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), but not creatine kinase B-type (CKB), has a direct interaction with ASB9 in human SSC line using protein immunoprecipitation experiments. Subsequently, we re-expressed HIF1AN in ASB9 overexpressing cells and found that HIF1AN reversed the proliferative and apoptotic changes induced by ASB9 overexpression. In addition, we found that ABS9 was significantly downregulated in some NOA patients, implying a correlation between ASB9 dysregulation and impaired spermatogenesis. Conclusion ASB9 is predominantly expressed in human SSCs, it affects the proliferation and apoptotic process of the SSC line through HIF1AN, and its abnormal expression may be associated with NOA.

Imaging characteristics and postoperative pathological analysis of bronchiolar adenoma / 中国胸心血管外科临床杂志

@#Objective    To analyze the pathological manifestations and imaging characteristics of bronchiolar adenoma (BA). Methods    The clinical data of 11 patients with BA who received surgeries in our hospital from January 2019 to September 2020 were retrospectively analyzed, including 5 males and 6 females aged 40-73 (62.40±10.50) years. The intraoperative rapid freezing pathological diagnosis, postoperative pathological classification, cell growth pattern, nuclear proliferation index Ki-67 and other immunohistochemical staining combined with preoperative chest CT imaging characteristics were analyzed. Results    The average preoperative observation time was 381.10±278.28 d. The maximum diameter of imaging lesions was 5-27 (10.27±6.34) mm. Eight (72.7%) patients presented with irregular morphology of heterogeneous ground-glass lesions, and 3 (27.3%) patients presented with pure ground-glass lesions. There were 10 (90.9%) patients with vascular signs, 8 (72.7%) patients with vacuolar signs, 1 (9.1%) patient with bronchus sign, 3 (27.3%) patients with pleural traction and 9 (81.8%) patients with burr/lobular sign. The surgical methods included sub-lobectomy in 10 patients and lobectomy in 1 patient. Five (45.5%) patients were reported BA by intraoperative frozen pathology. The postoperative pathological classification included 8 patients with distal-type and 3 patients with proximal-type, and the maximum diameter of the lesions was 4-20 (8.18±5.06) mm. Eight (72.7%) patients showed characteristic bilayer cell structure under microscope, and 10 (90.9%) patients showed thyroid transcription factor 1 expression in pathological tissues. The expression of NapsinA in intracavity cells was found in 9 (81.8%) patients. The Ki-67 index of the lesion tissue was 1%-5% (3.22%±1.72%). Conclusion    The pathological features and imaging findings of BA confirm the premise that BA is a neoplastic lesion. However, to identify BA as a benign or inert tumor needs more clinical data and evidence of molecular pathological studies.

Mental Health Status and Influencing Factors of Pediatricians in Guangzhou / 中山大学学报(医学科学版)

ObjectiveTo investigate the mental health of pediatricians in Guangzhou and its influencing factors， and to provide countermeasures for improving the mental health of pediatricians. MethodsA stratified random sampling method was used to randomly select 400 pediatricians in 11 districts of Guangzhou， and they were surveyed using the Symptom Check List（SCL-90） and the Job Stressor Scale. ResultsThe top three job stressors scored by pediatricians in Guangzhou were external environment （3.23±0.59）， workload （3.19±0.56）， and organizational management （2.74±0.55）. All factor scores were higher than those of the clinician group except for career interest， and the difference was statistically significant （P<0.01）. The number of pediatricians with mental health problems was 109， accounting for 27.25%. All factor scores were higher than the physician norm except for anxiety and paranoia. The correlations between each factor of work stressors and each factor of SCL-90 were positive and statistically significant （P<0.05）， except for two pairs of factors， workload and terror as well as external environment and terror. The results of univariate analysis showed statistically significant differences in the mental health scores of pediatricians with different health status， years of work experience， job satisfaction， job stress， and career prospects （P<0.05）. The results of multiple linear regression showed that health status， years of work experience， professional interest， interpersonal relationship， and doctor-patient relationship were influential factors in the mental health of pediatricians （P<0.05）. ConclusionThe mental health of pediatricians in Guangzhou is unsatisfactory， and the factors affecting them are mainly external objective factors such as workload and organizational management.

Clinical features and correlation analysis of the 24h intraocular pressure and water drinking test in patients with primary open angle glaucoma and ocular hypertension / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To summarize the clinical features of the 24h intraocular pressure data and the water drinking test(WDT)results in patients with primary open angle glaucoma(POAG)and ocular hypertension(OHT), and analyze the correlation.METHODS: To collect the data of 87 cases(174 eyes)with POAG and OHT, who had completed 24h intraocular pressure(IOP)(measured every 2h)and WDT(drink 1 000mL water off within 5min and then measure every 15min within 1h)in the ophthalmology department of Shenzhen University General Hospital from December 2019 to March 2022. They were divided into three groups, with 33 cases(66 eyes)in high tension glaucoma(HTG)group, 28 cases(56 eyes)in normal tension glaucoma(NTG)group and 26 cases(52 eyes)in OHT group. The clinical features of 24h IOP and WDT among the patients in three groups were summarized, and Spearman correlation was used to analyze the peak and fluctuation values of IOP.RESULTS: Clinical features among the patients in three groups:(1)the proportion of peak IOP of HTG, NTG and OHT group:(2:00-6:00 a.m.): 40.9%, 23.2% and 26.9%;(8:00-12:00 a.m.): 34.8%, 46.4% and 55.8%;(14:00-18:00 p.m.): 18.2%, 21.4% and 11.5%;(20:00-24:00 p.m.): 6.1%, 8.9% and 5.8%. Valley proportion among groups: early morning: 21.2%, 25.0% and 30.8%; morning: 22.7%, 10.7% and 13.5%; afternoon: 19.7%, 17.9% and 17.3%; evening: 36.4%, 46.4% and 38.5%. The proportion of 24h IOP fluctuation &#x0026;#x003C;6mmHg: 9.1%, 62.5% and 17.3%; 6-&#x0026;#x003C;8mmHg: 24.2%, 32.1% and 40.4%; ≥8mmHg: 66.7%, 5.4% and 42.3%.(2)WDT: The proportion of the three groups that could reach peak IOP within 30min was 81.8%, 76.8% and 80.8%, respectively. The proportion of IOP fluctuations in the three groups &#x0026;#x003C;6mmHg: 10.6%, 78.6% and 38.5%; 6-&#x0026;#x003C;8mmHg: 22.7%, 16.1% and 28.8%; ≥8mmHg: 66.7%, 5.4% and 32.7%.(3)the proportions of WDT peak higher than 24h peak IOP in the three groups were 80.3%, 80.4% and 80.8%. Correlation: the peak values of 24h IOP were positively correlated with the peak values of WDT(all P&#x0026;#x003C;0.01), the fluctuation of 24h IOP was positively correlated with the fluctuation of WDT in HTG and OHT group(P&#x0026;#x003C;0.01, P&#x0026;#x003C;0.05), while it showed no significant correlation in NTG group(P&#x0026;#x003E;0.05).CONCLUSION: Diurnal measurements of IOP during office hours(08:00 a.m.-18:00 p.m.)may fail to capture the peak values and underestimate IOP fluctuations. The 24h IOP fluctuation ≥HTG group of 8mmHg&#x0026;#x003E;OHT group&#x0026;#x003E;NTG group. The peak WDT in over 75% patients could be achieved within 30min, and it was higher than 24h peak IOP of over 80% patients. There was a positive correlation between the 24h IOP fluctuations and the WDT fluctuations in HTG and OHT patients. Therefore, WDT has clinical significance in assessing fluctuations in patients' IOP.

Exploration on "Efficacy-toxicity" Association Mechanisms of Tripterygium wilfordii Polyglycoside Tablets Against Rheumatoid Arthritis Based on Multi-omics Integrated Regulatory Network / 中国实验方剂学杂志

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.

Systematic Review on Safety of Chinese Medicines Combined with Tripterygium wilfordii Preparations in Treatment of Rheumatoid Arthritis and Exploration on Underlying Network Regulatory Mechanisms of Enhancing Efficacy and Reducing Toxicity / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the safety of Chinese medicines combined with Tripterygium wilfordii polyglycoside tablets/Tripterygium wilfordii tablets （TWPT/TWT） in the treatment of rheumatoid arthritis （RA）， and to explore the network regulatory mechanisms of enhancing efficacy and reducing toxicity of commonly used combination regimes. MethodThe literature involving the adverse reactions of TWPT/TWT in treating RA was searched and collected from three Chinese databases （CNKI， Wanfang Data， VIP） and three English databases （PubMed， Cochrane Library， Embase） from the inception of the databases to July 2021. All studies were assessed by the Cochrane risk of bias tool， and the data were extracted and analyzed by Stata 15.0. Furthermore， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine 2.0 （TCMIP v2.0，http：//www.tcmip.cn/） was used to construct a "drug target-symptom gene of efficacy and toxicity" interaction network， to explore the underlying network regulatory mechanisms of enhancing efficacy and reducing toxicity of common T. wilfordii preparation combinations. ResultA total of 2 132 articles on Chinese medicines combined with TWPT/TWT in the treatment of RA were retrieved， and 18 of them were finally included. The systematic review showed that the adverse reactions of TWPT/TWT against RA mainly occurred in the digestive system， blood system， and reproductive system， of which digestive system had the highest incidence of damages. However， the combination with Chinese medicines effectively alleviated the adverse reactions caused by TWPT/TWT ［RR （95% CI）=0.45 （0.30， 0.66）， P<0.01］. In addition， the subgroup analysis indicated that the age of RA patients， course of disease， combination regimen， medication dosage and duration of treatment all affected the occurrence of adverse reactions of TWPT/TWT. It was found in clinical studies that total glucosides of paeony （TGP） and TWPT/TWT was most widely combined， and the effect of TGP in reducing TWPT/TWT-induced hepatotoxicity was also more significant than that of other Chinese medicines. Moreover， taking this combination regime as an example， this paper explored the "efficacy-toxicity" association mechanisms of TGP-TWPT/TWT against RA. The "drug target-symptom gene of efficacy and toxicity" interaction network revealed that the core network targets of TGP-TWPT/TWT enhanced efficacy and reduced toxicity mainly through regulating immunity-inflammation-related pathways， metabolic pathways and cell signal transduction. Especially， interleukin-4 （IL-4） and interleukin-13 （IL-13）， which were involved in the "immunity-inflammation" module， were the common targets of TGP-TWPT/TWT to enhance efficacy and reduce toxicity. The endogenous sterols， bile acids and bile salts， insulin secretion and other metabolic pathways in the "body metabolism" module were closely associated with the mechanisms of TWPT/TWT inducing hepatotoxicity and TGP reducing hepatotoxicity. While cell function regulation pathways， such as stem cell factor （SCF）/tyrosine kinase receptor （KIT） signaling pathway and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）signaling pathway were involved in both anti-RA effects and hepatotoxicity of TWPT/TWT. ConclusionClinical application of suitable Chinese medicines combined with TWPT/TWT in the treatment of RA can effectively improve the rheumatism and reduce the adverse reactions of TWPT/TWT， and TGP-TWPT/TWT has the most significant toxicity-reducing effect. Further biological network-based investigation indicates that the toxicity-reducing mechanism of TGP-TWPT/TWT may be related to the regulation of interleukin signaling pathway and bile acid metabolism pathway， and the synergistic efficacy-enhancing effect of the combination may be achieved by acting on interleukin signaling pathway and cell function regulation pathway.

Preliminary exploration of SpyGlass direct visualization system in diagnosis and treatment of biliary stricture after liver transplantation / 器官移植

Objective To preliminarily evaluate the application value of SpyGlass direct visualization system in the diagnosis and treatment of biliary stricture after liver transplantation. Methods Clinical data of 4 patients presenting with biliary stricture after liver transplantation who underwent SpyGlass direct visualization system examination were collected. The examination, treatment and prognosis of biliary stricture were analyzed. Results The examination results of color Doppler ultrasound, magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) in 4 patients suggested biliary anastomotic stricture with intrahepatic biliary dilatation, and 2 of them were complicated with intrahepatic biliary calculi. Repeated placement of biliary stent under ERCP yielded poor effect in 3 cases. SpyGlass direct visualization system examination hinted biliary anastomotic stricture in 4 patients, 3 cases of intrahepatic biliary dilatation, 3 cases of intrahepatic biliary calculi, 2 cases of purulent bile and 3 cases of floccules within the biliary tract, 1 case of congestion and edema of biliary tract wall and 2 cases of local epithelial necrosis and stiffness changes of intrahepatic biliary tract wall. The wire could not be inserted in 1 patient due to severe biliary anastomotic stricture. Four patients were treated with biliary stricture resection + biliary stone removal + biliary end-to-end anastomosis, biliary stricture resection + biliary-intestinal anastomosis, ERCP lithotomy + biliary metal stent implantation, and biliary metal stent implantation + percutaneous transhepatic bile duct lithotomy, respectively. Relevant symptoms were relieved without evident complications. All patients survived during the follow-up until the submission date. Conclusions Compared with traditional imaging examination, SpyGlass direct visualization system may more directly display the morphological characteristics of biliary tract wall and structural changes within biliary tract cavity, which is an effective examination tool for biliary stricture after liver transplantation. In addition, individualized treatment methods may be adopted for different biliary tract diseases, which is expected to improve clinical prognosis of patients.

Study on the improvement of quality standard for Tibetan medicine Qinjiaohua / 中国药房

OBJECTIVE To improve the quality standard of T ibetan medicine of Qinjiaohua ，and to provide scientific basis for comprehensive quality evaluation. METHODS The qualitative analysis of 16 batches of Qinjiaohua with different producing areas and different origins was carried out by microscopic and TLC identification. According to the method stated in 2020 edition of Chinese Pharmacopoeia ，water content ，total ash content ，acid-insoluble ash content and alcohol-soluble extract content were determined. HPLC method was used to determine the contents of 5 components （loganic acid ，swertiamarin，gentiopicrin， swertionolin，isoorientin） in Qinjiaohua. RESULTS The medicinal powder of Qinjiaohua was light brown-yellow ，and the microscopic features of the powder were clear ，and pollen grains ，ducts，non-glandular hairs ，corolla epidermal cells and calyx epidermal cells were all found. The results of TLC indentification showed that there were fluorescent spots of the same color in the chromatogram of the tested product and the corresponding position of substance control （isoorientin）. The content ranges of water content，total ash content ，acid-insoluble ash content and alcohol-soluble extract were 5.40％-8.87％，3.76％-6.40％，0.27％-0.58％， 26.81％-42.51％，respectively. The results of content determination methodology met the requirements of pharmacopoeia ；the content ranges of loganic acid ，swertiamarin，gentiopicrin，swertionolin and isoorientin in 16 batches of Qinjiaohua were 3.13-9.36，1.26-22.39，13.80-74.60，1.24-12.22，2.58-14.96 mg/g，respectively. CONCLUSIONS On the basis of the original quality standard of Qinjiaohua ，microscopic identification ，TLC identification ，content determination and examination items of water，total ash ，acid-insoluble ash and alcohol-soluble extract are added. It is preliminarily proposed that water content ，total ash content and acid-insoluble ash content should not exceed 9.0％，6.5％ and 0.6％，while the contents of ethanol-soluble extract and gentiopicrin should not be less than 26.0％ and 13.8 mg/g，respectively.

Effect of enteral nutrition support on hematological complications in children with malignant solid tumor during chemotherapy / 中华全科医师杂志

Objective:To investigate the effect of enteral nutrition on hematological complications in children with malignant solid tumors during chemotherapy.Methods:A total of 103 children with malignant solid tumor admitted to our hospital from March 2020 to December 2020 were enrolled in the study. The children were randomly divided into enteral nutrition group ( n=51) and control group ( n=52). Children in enteral nutrition group were given enteral nutrition support on the basis of routine diet, while children in control group were only given routine diet. The levels of leukocytes, neutrophils, hemoglobin and platelets in peripheral blood of children during chemotherapy were analyzed. The incidence of infection and the transfusion of red blood cells and platelets after chemotherapy were documented and compared between two groups. Results:The levels of white blood cells, neutrophils, hemoglobin and platelets before chemotherapy were significantly higher than those after chemotherapy both in enteral nutrition group ( Z=-5.91, -5.59, -5.54, -5.66, all P<0.05) and in control group ( Z=-6.14, -5.84, -5.75, -4.75, all P<0.05). The overall hemoglobin levels in enteral nutrition group before and after chemotherapy was significantly higher than those in control group ( t=5.68, 5.62, P<0.05), and there were no significant differences in the levels of white blood cells, neutrophils and platelets between the two groups before chemotherapy ( Z=-0.71, -0.12, -1.29, all P>0.05) and after chemotherapy ( Z=-0.39, -0.86, -0.94, all P>0.05). Compared with the control group, the degree of anemia during chemotherapy was significantly improved in enteral nutrition group (χ2=10.45,6.12, all P<0.05), but there was no significant difference in the reduction degree of white blood cells, neutrophils and platelets between the two groups (before chemotherapy: χ2=1.17, 0.10, 0.49; after chemotherapy: χ2=0.18, 1.10, 0.97, all P>0.05). The number of children receiving red blood cell transfusion in enteral nutrition group was significantly lower than that in control group (χ2=14.06, P<0.05), and there was no significant difference in the number of children with infection and platelet transfusion between the two groups (χ2=1.20, 0.29, all P>0.05).There was no significant difference in the duration of neutrophil deficiency between enteral nutrition group and control group ( t=-1.75, P>0.05). Conclusion:Enteral nutrition support can significantly improve the hemoglobin level in children during chemotherapy, effectively alleviate the severity of anemia, and reduce the incidence of red blood cell transfusion after chemotherapy, which has high clinical application value.

Primary renal synovial sarcoma: a case report / 中华泌尿外科杂志

Synovial sarcoma is a soft tissue malignancy of unknown origin which usually occurs around the joints of the extremities, but rarely detected in the kidneys. A case of primary synovial sarcoma of the kidney was reported, which was preoperatively diagnosed as a malignant tumor of the right kidney for intermittent gross hematuria. After the laparoscopic radical nephrectomy, primary renal synovial sarcoma was confirmed by pathological examination. The patient refused further treatment, and there was no recurrence or metastasis during the 13 months of follow-up.

Effects of ginsenoside Rg1 on the expression of neuronal autophagosome-related proteins in brain slices of a rat model of Alzheimer's disease / 中华老年医学杂志

Objective:To explore the effects and molecular mechanisms of ginsenoside Rg1 on the expression of neuronal autophagosome-related proteins in a rat model of Alzheimer's disease(AD).Methods:Six-week-old SD rats were decapitated to prepare hippocampal brain slices.The slices were randomly divided into the blank control group, the model group, the low-concentration, medium-concentration and high-concentration Rg1 groups, with 10 in each group.In the model group, Aβ 1-42(final concentration: 5 μmol/L)was added into an artificial cerebrospinal fluid(CSF)for 2 h treatment.The low-concentration, medium-concentration and high-concentration Rg1 groups were treated with Aβ 1-42(final concentration: 5 μmol/L)for 2 h, and then treated with Rg1(final concentrations: 60 μmol/L, 120 μmol/L, 240 μmol/L, respectively)for 3 h. The blank control group was not given any intervention drugs.At the end of intervention, histological changes of hippocampal brain slices in each group were examined via hematoxylin-eosin(HE)staining.Autophagosomes in hippocampal brain slices of each group were detected using transmission electron microscopy.The expression levels of autophagy-related proteins(P62, LC3-Ⅱ/LC3-Ⅰ), Aβ 1-42and shank protein in hippocampal brain slices of each group were detected with Western blot. Results:The results of HE staining showed that the arrangement of hippocampal neurons were disordered in the model group, with death and depletion of neurons.The arrangement and depletion of hippocampal neurons in each Rg1 group were less severe compared with the model group, with most significant improvement seen in the high-concentration Rg1 group.The results of transmission electron microscopy showed that the number of autophagosomes in brain slices in the model group was significantly higher than that in the blank control group, while each Rg1 group had fewer autophagosomes than the model group.The results of Western blot showed that, compared with the blank control group, levels of Shank1, P62 and LC3-Ⅰ proteins in brain slices were decreased(all P<0.05), while levels of Aβ 1-42and LC3-Ⅱ protein were significantly increased(all P<0.05)in the model group.Compared with the model group, levels of Shank1, P62 and LC3-Ⅰ proteins in brain slices were increased(all P<0.05), while levels of Aβ 1-42and LC3-Ⅱ protein were decreased( P<0.05)in each Rg1 group.These changes were the most significant in the high-concentration Rg1 group. Conclusions:Ginsenoside Rg1 may inhibit autophagy by up-regulating the expression of Shank1, P62 and LC3-Ⅰ proteins in hippocampal brain slices of rats in the AD model, thus playing protective roles in brain neurons.

Time-resolved fluorescence immunochromatographic assay for the detection of mycoplasma pneumoniae IgM and IgG / 中华核医学与分子影像杂志

Objective:To establish time-resolved fluorescence immunochromatographic assay (TFICA) for rapid and quantitative detection of mycoplasma pneumoniae (MP) immunoglobulin (Ig)M and IgG.Methods:Based on capillary effect and europium nanospheres, rapid TFICA for MP-IgM and IgG detections were developed with the optimized parameters (coupling rates of antigens or antibodies to microspheres, dilution of labeled nanospheres, fixture concentrations on test line and serum dilutions). The methodological performances were estimated such as sensitivity, specificity, stability. By testing 55 healthy control samples, the reference values of TFICA were obtained. The reliability was evaluated by Kappa test from detecting sera of 88 cases (33 patients and 55 healthy controls) using TFICA and commercial kits by chemiluminescence immunoassays (CLA). Results:After screening the assay conditions, the mass ratios of mouse anti-human IgG and MP antigen with nanospheres were 1∶20 and 1∶100 respectively; the work dilutions of nanobeads conjugated with anti-human IgG and MP antigen were 1∶200 and 1∶100 respectively; the spraying concentrations of MP antigen and goat anti-human IgM were 0.5 and 1.0 g/L on the test line respectively, and the working dilutions of serum sample were both 1∶300. In the MP-IgM and IgG detections, the linear working ranges were (0.78-70.00)×10 3 relative unit (RU)/L and (0.17-200.00)×10 3 RU/L, while the sensitivities of the assays were 0.78×10 3 and 0.17×10 3 RU/L, respectively. No cross reactions were found with antithyroid peroxidase antibody, anticardiolipin antibody or thyroglobulin antibody. In these MP-IgM and IgG assays, the relative standard deviations were 3.7%-14.8% and 2.9%-14.0%, the average reduction rates of fluorescence were 13.7% and 14.2% respectively after incubation at 37 ℃ for 5 d. The reference values of MP-IgM and IgG were 3.33×10 3 and 2.61×10 3 RU/L, while the Kappa values between TFICA and CLA were 0.79 and 0.76, respectively. Conclusion:TFICA is a simple, sensitive, specific and quantitative method for detecting MP-IgM and IgG antibodies, and may show great promise for future clinical use.

Study on quality control of mediastinal shift radiotherapy with target volume after operation for non-small cell lung cancer / 中华放射肿瘤学杂志

Objective:To analyze the mediastinal displacement of target volume in the postoperative radiotherapy (PORT) process for non-small cell lung cancer (NSCLC) and the value of mid-term evaluation.Methods:For 100 patients with postoperativeN 2 stage NSCLC, R 1-2 and any N staging, bone anatomy was utilized to measure the change of the first and second CT localization on the same level. Statistical analysis were performed using the WilCoxon, Kruskal-Wallis and χ2 tests. The cut-off values were calculated with the receiver operating characteristic (ROC) curve. Results:Among the included patients, in the PORT process, the mediastinal displacement in the x (front and rear), Y (left and right) and Z (upper and lower) directions were 0.04-0.53 cm, 0.00-0.84 cm and 0.00-1.27 cm, respectively, and the order of mediastinal displacement distance wasz > Y> X,respectively. According to the ROC curve calculation, the cut-off values were 0.263, 0.352 and 0.405, respectively, which were greater than the cut-off values in 25 cases (25%), 30 cases (30%) and 30 cases (30%), respectively. There was significant difference in the three-dimensionalmediastinal displacement ( P=0.007, <0.001 and<0.001). The mediastinal displacement in thex, Y and Z directions had no statistical significance regarding resection site ( P=0.355, 0.239 and 0.256) and operation mode ( P=0.241, 0.110 and 0.064). Comparative analysis of modified whole group mediastinal shift> and cut-off values, medium-simulation (m-S) and the originally planned radiotherapy shown that there was no significant difference in the incidence of radiation esophagitis (RE) and radiation pneumonitis in PORT patients (all P>0.05); however, the incidence of ≥grade 3 RE in the modified plan after m-S was significantly lower than that in the originally planned PORT patients, which were 0 and 7%, respectively ( P<0.001). Conclusions:Mediastinal displacement exists in the PORT process of N 2 or/and R 1-2 cases after radical operation of NSCLC, and obvious movement occurs in 20%-30% of patients. Relocating and modifying the target volume and radiotherapy plan in the middle of the PORT process is beneficial to quality assurance and quality control.

Chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar affect diversity of gut microbiota in rat model of malignant ascites induced by Walker-256 cells / 中国中药杂志

This study aims to explore the effects of chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar on the diversity of gut microbiota in the rat model of malignant ascites, identify the key differential microbial taxa, and reveal the biological mechanism of water-expelling effect of the two chemical ingredient groups. The rat model of malignant ascites induced by Walker-256 cells was established, and phenolphthalein was used as the positive drug. The rats were orally administrated with corresponding agents for consecutive 7 days. On day 6, fresh feces samples were collected from the rats, and 16 S rDNA high-throughput sequencing and GC-MS were employed to determine the composition of gut microbiota and the content of short-chain fatty acids, respectively. On day 7, serum and intestinal tissue samples were collected for the determination of related indicators. Compared with the control group, the model group showed decreased feces volume and urine volume(P<0.01), increased volume of ascites and levels of Na~+, K~+, and Cl~- in urine(P<0.01), down-regulated mRNA and protein levels of intestinal AQP8(P<0.01), lowered abundance of beneficial Lactobacillus(P<0.01) while risen abundance of potential pathogenic Lachnospiraceae and Anaeroplasma(P<0.01), and reduced content of short-chain fatty acids(P<0.01). Compared with the model group, administration with chemical ingredient groups B and C alleviated all the above indicators(P<0.01). In conclusion, chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar could alleviate the disordered gut microbiota in rats with malignant ascites to expel water through increasing the abundance of beneficial Lactobacillus and reducing the abundance of harmful Lachnospiraceae and Anaeroplasma. This study can provide a reference for the reasonable clinical application of Kansui Radix stir-fried with vinegar.

Mechanism of Tibetan medicine Pterocephalus hookeri extract in treatment of rheumatoid arthritis based on serum metabonomics / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.

Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evalvate efficacy of Qizi Yusi Pills (QYP), a Chinese medicine compound preparation, on in vitro fertilization-embryo transfer (IVF-ET) in women of advanced reproductive age.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled trial was conducted from June 2018 to October 2019. A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design, with 62 patients in each group. All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist (GnRH-a) long protocol. As the QYP group, QYP was administered while the control group received placebo. QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval. Both medications were taken orally at doses of 10 g three times each day. The primary outcome was cumulative pregnancy rate, and the secondary outcomes were periodic medication, follicular status, serum hormone and endometrial receptivity. Follow-up continued until 4 weeks after delivery. Maternal and neonatal complications, such as gestational diabetes, were also observed.@*RESULTS@#Overall, 119 patients completed the study, 60 in the QYP group and 59 in the placebo group. Per protocol (PP) analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group [43.33% (26/60) vs. 25.42% (15/59), P=0.040). Additionally, more oocytes were retrieved from the QYP group than those from the placebo group (8.95 ± 3.12 vs. 7.85 ± 1.91, P=0.022). Moreover, the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group (11.78 ± 2.27 mm vs. 10.68 ± 2.07 mm, P=0.012). Maternal and neonatal complications between the two groups were not significantly different (P>0.05). Intention-to-treat analysis was in line with PP results.@*CONCLUSIONS@#QYP can enhance ovarian reserve capacity and ovarian response, and possibly promote endometrial receptivity. QYP effectively improves cumulative pregnancy rates in older patients (⩾35 years) undergoing IVF-ET. (Registration No. ChiCTR1800014427).

Clinical observation of rimazolom for painless gastroscopy sedation in outpatients / 中国药房

OBJECTIVE To obser ve the efficacy and safety of rimazo lom for painless gastroscopy sedation in outpatients. METHODS Totally 84 patients who underwent painless gastroscopy were collected from the outpatient department of the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from March to June in 2021. By random number table method combined with envelope allocation concealment method ，they were randomly divided into observation group and control group ，with 42 cases in each group. The patients in the observation group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+Rimazole toluenesulfonate for injection 0.2 mg/kg. Patients in the control group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+ Propofol emulsion injection 2 mg/kg. Gastroscopy was performed after the patient ’s consciousness disappeared. The sedative efficiency，sedative onset time ，recovery time and the occurrence of adverse drug reaction were observed in 2 groups. The heart rate（HR），mean arterial pressure （MAP），pulse oxygen saturation （SpO2），modified observer ’s assessment of alertness/sedation （MOAA/S）score and Narcotrend score were recorded in 2 groups after entering the room （T0），after anesthesia induction （T1）， when gastroscope entered the throat （T2），at the end of gastroscope withdrawal （T3），5 min after gastroscopy （T4）. RESULTS There was no significant difference in the effective rate of sedation （100％），the incidence of respiratory depression ， nausea and vomiting between the two groups （P＞0.05）. The qq.com onset time of sedation in the observation group was longer than control group ，and the recovery time and the incidence ofhypotension，hypotension to be tre ated，injection pain and bradycardia in observation group were significantly shorter or lower than control group （P＜0.05）. At T 0，there was no significant difference in HR ，MAP，SpO2，MOAA/S score or Narcotrend score between two groups （P＞0.05）. From T 1 to T 4，the HR of control group was significantly lower than that of the same group at T 0，and significantly lower than observation group at the same time（P＜0.05）. From T 1 to T 3，the MAP of two groups were significantly lower than the same group at T 0（P＜0.05），but there were no significant differences between two groups and between T 4 and T 0（P＞0.05）. There was no significant difference in SpO 2 at different time points between two groups and HR at different time points in observation group （P＞0.05）. From T 1 to T 3，MOAA/S score and Narcotrend score of two groups were significantly lower than the same group at T 0，while the MOAA/S score and Narcotrend score at T 1 and T 3 and Narcotrend score at T 3 of observation group were significantly higher than control group at the same time （P＜0.05），and the Narcotrend score of observation group at T 2 was significantly lower than control group at the same time（P＜0.05）；at T 4，there were no significant differences in MOAA/S score and Narcotrend score between two groups （P＞ 0.05）. CONCLUSIONS Remazolam shows good sedative effect and safety for painless gastroscopy.

Hypertriglyceridemia: A Neglected Risk Factor for Ischemic Stroke? / 대한뇌졸중학회지

Hypertriglyceridemia is caused by defects in triglyceride metabolism and generally manifests as abnormally high plasma triglyceride levels. Although the role of hypertriglyceridemia may not draw as much attention as that of plasma cholesterol in stroke, plasma triglycerides, especially nonfasting triglycerides, are thought to be correlated with the risk of ischemic stroke. Hypertriglyceridemia may increase the risk of ischemic stroke by promoting atherosclerosis and thrombosis and increasing blood viscosity. Moreover, hypertriglyceridemia may have some protective effects in patients who have already suffered a stroke via unclear mechanisms. Therefore, further studies are needed to elucidate the role of hypertriglyceridemia in the development and prognosis of ischemic stroke.

Treatment of dacryocystorhinostomy and intubation under nasal endoscope on recurrent dacryocystitis after removal of artificial nasolacrimal duct / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the proportional distribution of the size of lacrimal sac in recurrent dacryocystitis after the removal of artificial nasolacrimal duct and the clinical effect of dacryocystorhinostomy under nasal endoscope on patients with recurrent dacryocystitis.METHODS: Totally 73 patients(73 eyes)with recurrent dacryocystitis after removal of artificial nasolacrimal duct in our hospital from January 2018 to November 2019 were retrospectively studied. All patients underwent dacryocystography after hospitalization, and then performed dacryocystorhinostomy combined with intubation of double- artificial nasolacrimal duct under nasal endoscope and general anesthesia. The size of lacrimal sac was measured, and the area and effective rate of fistula were analyzed respectively at 2wk, 1, 3 and 6mo after operation. RESULTS: There were 13 eyes with large dacryocyst(Transverse diameter > 5mm, 18%), 26 eyes with middle dacryocyst(Transverse diameter between 2-5mm, 36%), and 34 eyes with small dacryocyst(Transverse diameter <2mm, 47%); There was significant difference in the stoma area of dacryocystostomy at 2wk, 1, 3, 6mo respectively(<i>P</i><0.05); Compared with 2wk, 1, 3mo after operation, the stoma area at 6mo after operation significantly decreased by 14.08±0.68, 10.49±0.75, 0.31±0.23mm2(all <i>P</i><0.05); The curative rates were 100%, 93%, 88% and 85% at 2wk, 1, 3, 6mo after operation, respectively. CONCLUSION: After the removal of the artificial nasolacrimal duct, the majority of the patients with recurrent dacryocystitis typically featured medium and small lacrimal sac. The curative effect of this type of recurrent dacryocystitis by dacryocystorhinostomy and intubation under nasal endoscope was proved to be effective, which could serve as a proper and better choice in clinic practice.

Relationship between immune indexes and prognosis in patients with sepsis: data analysis based on MIMIC-Ⅳ database / 中华危重病急救医学

Objective:To investigate the relationship between the changes of immune indexes and prognosis in patients with sepsis.Methods:Based on the hospitalization information from 2008 to 2019 in the American Medical Information Mart for Intensive Care-Ⅳ v2.0 (MIMIC-Ⅳ v2.0), the hospitalized data including CD3 count, CD4 count, CD8 count, CD4/CD8 ratio, immunoglobulins (IgA, IgG, IgM) levels and lymphocyte counts, gender, age, body mass index (BMI), sequential organ failure assessment (SOFA), and prognosis of patients with coronary heart disease, hypertension, diabetes mellitus, underlying diseases, and 28-day prognosis were collected. The immunological indexes affecting the prognosis of patients with sepsis were compared and analyzed. The receiver operator characteristic curve (ROC curve) was drawn to analyze the value of immunological indexes in predicting the 28-day prognosis of patients with sepsis.Results:A total of 33 745 patients were enrolled in the study, including 1 509 cases of sepsis and 32 236 cases without sepsis. Among the patients with sepsis, there were 1 084 cases alive and 425 cases died within 28 days. BMI (kg/m 2: 33.25±28.71 vs. 28.90±15.28) and IgA levels within 3 days and 7 days after admission in sepsis group were significantly higher than those in the non-sepsis group [within 3 days after admission: (275.01±216.96) mg/L vs. (85.99±75.76) mg/L; within 7 days after admission: (275.01±216.96) mg/L vs. (85.99±75.76) mg/L, all P < 0.05]. CD3 count, CD8 count within 3 days and 7 days after admission in sepsis group were significantly lower than that in the non-sepsis group [within 3 days after admission: CD3 counts were (1 080.74±849.23)/μL vs. (1 242.91±889.24)/μL, CD8 counts were (558.07±368.77)/μL vs. (625.07±529.66)/μL; within 7 days after admission: CD3 counts were (1 079.69±850.61)/μL vs. (1 242.48±889.23)/μL, CD8 counts were (556.70±467.23)/μL vs. (624.93±429.78)/μL, all P < 0.05]. The proportion of patients with hypertension, diabetes and coronary heart disease were significantly higher than those in the non-sepsis group [hypertension: 10.07% (152/1 509) vs. 2.47% (796/32 236), diabetes: 50.10% (756/1 509) vs.15.18% (4 895/32 236), coronary heart disease: 31.21% (471/1 509) vs. 19.19% (6 186/32 236), all P < 0.05]. In the sepsis group, the CD3 count, CD4 count and CD4/CD8 ratio in the survival group were significantly higher than those in the death group within 3 days and 7 days after admission [within 3 days after admission: CD3 counts were (1 127.20±857.14)/μL vs. (938.26±810.50)/μL, CD4 counts were (559.76±507.18)/μL vs. (338.75±267.11)/μL, CD4/CD8 ratios were 1.87±0.80 vs. 1.02±0.12; within 7 days after admission: CD3 count were (1 124.01±810.53)/μL vs. (943.78±808.21)/μL, CD4 count were (559.56±507.36)/μL vs. (341.95±266.56)/μL, CD4/CD8 ratios were 1.88±0.79 vs. 1.03±0.13, all P < 0.05]. The area under the ROC curve (AUC) of CD4/CD8 ratio within 3 days after admission in predicting the prognosis of septic patients at 28 days was 0.615 [95% confidence interval (95% CI) was 0.555-0.671], the sensitivity was 70.83%, and the specificity was 52.49%. Conclusions:Hypertension, coronary heart disease and diabetes are more likely to induce sepsis. The changes of immune indexes in patients with sepsis will occur in the early stage. Early CD4/CD8 index can predict the prognosis of patients with sepsis to a certain extent.