Research Analysis of SLC12A3 Gene Mutation and Molecular Mechanism in Gitelman Syndrome / 罕见病研究

ObjectiveThis study aimed at conducting retrospective analysis of the clinical symptoms and genetic mutations in 20 children with Gitelman syndrome treated at the Affiliated Children′s Hospital of Nanjing Medical University from August 2015 to November 2022 and also explored the molecular mechanism of the pathogenic high-frequency mutation D486N in the Chinese population.MethodsWe collected the clinical manifestations, growth and development status, laboratory examination results, and SLC12A3 gene variations of the patients. We distinguished the wild-type and mutant SLC12A3 genes overexpressed in human embryonic kidney 293T cells (HEK293T). We used protein immunoblotting to detect the expression level of NCC, and used immunofluorescence techniques to examine the subcellular localization of NCC. In addition, we investigated the impact of the high-frequency SLC12A3 gene mutation D486N on NCC protein expression and localization.ResultsIn the 20 patients with Gitelman syndrome, all of them had hypokalemia. We indemnified twenty-six SLC12A3 gene mutations, 13 of which are missense mutation, 1 of which synonymous mutation, 1 nonsense mutation, 4 frameshift mutation, and 7 splicing site mutation. Among them, four mutations (p.T235K, c.1096-1G > A, p.A464A, and c.2660+1_2660+2insT) were novel mutations.ConclusionsWe found the preliminary evidence that the high-frequency mutation D486N in the Chinese population affected the expression of total and membrane-bound NCC protein and influenced the membrane localization of NCC protein. The findings of this study provides experimental evidence for genetic counseling, diagnosis, and treatment of Gitelman syndrome.

Ancient Literature Analysis and Modern Clinical Application of Famous Classical Formula Huagaisan / 中国实验方剂学杂志

ObjectiveTo sort out the historical evolution， prescription evolution and modern clinical application of Huagaisan. MethodHuagaisan and its synonym Huagaitang are used as keywords to search the databases of Traditional Chinese Medicine Think Tank， Chinese Medical Dictionary， Airusheng Chinese Medical Database and China National Knowledge Infrastructure（CNKI）. According to the inclusion and exclusion criteria， we obtained the information of ancient books and modern clinical research literature related to Huagaisan， and systematically reviewed and analyzed the historical origin， prescription composition， preparation method， dosage， efficacy， medicinal material origin， processing method and modern clinical application of Huagaisan. ResultA total of 198 pieces of ancient book information were included， involving 93 ancient Chinese medicine books. Huagaisan was composed of fried Perillae Fructus， red Poria， fried Mori Cortex， Citri Eoxcarpium Rubrum， stir-fried Armeniacae Semen Amarum， Ephedrae Herba and fried Glycyrrhizae Radix et Rhizoma， which had the efficacy of promoting the lungs and relieving epidemiological symptoms， expelling phlegm and relieving cough， and treating cough with wind-cold bundled epidemiological symptoms and stagnation of phlegm and Qi. The preparation method was suggested as boiling powder， crushing the seven herbs into coarse particles， the dosage of each drug was fried Perillae Fructus of 1.27 g， red Poria of 1.27 g， fried Mori Cortex of 1.27 g， Citri Eoxcarpium Rubrum of 1.27 g， stir-fried Armeniacae Semen Amarum of 1.27 g， Ephedrae Herba of 1.27 g and fried Glycyrrhizae Radix et Rhizoma of 0.64 g， taking 8.26 g when decocting， adding 300 mL of water， decocting to 210 mL， removing the dregs， and taking it warmly after meals. Twenty-one clinical research papers were included to analyze the modern clinical application of Huagaisan， which was mainly used in the treatment of respiratory diseases such as pneumonia， asthma， bronchitis and so on. ConclusionThis paper has verified and summarized the key information of the famous classical formula Huagaisan， which can provide a detailed reference basis for the development and clinical application of its compound preparation.

Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis / 世界急诊医学杂志（英文）

@#BACKGROUND: Xuebijing (XBJ) can alleviate the inflammatory response, improve organ function, and shorten the intensive care unit (ICU) stay in patients with pyogenic liver abscess (PLA) complicated with sepsis, but the molecular mechanisms have not been elucidated. This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach. METHODS: The active ingredients and targets of XBJ were retrieved from the ETCM database. Potential targets related to PLA and sepsis were retrieved from the GeneCards, PharmGKB, DisGeNet, Online Mendelian Inheritance in Man (OMIM), Therapeutic Targets Database (TTD), and DrugBank databases. The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets. Protein-protein interaction networks were analyzed using the STRING database. Potential treatment targets were imported into the Metascape platform for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was performed to validate the interactions between active ingredients and core targets. RESULTS: XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis. Interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF) were identified as core targets. KEGG enrichment analysis revealed important pathways, including the interleukin-17 (IL-17) signaling pathway, the TNF signaling pathway, the nuclear factor-kappa B (NF-κB) signaling pathway, and the Toll-like receptor (TLR) signaling pathway. Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets. CONCLUSION: XBJ may exert therapeutic effects on PLA complicated with sepsis by modulating signaling pathways, such as the IL-17, TNF, NF-κB, and TLR pathways, and targeting IL-1β, IL-6, and TNF.

miR-185-5p alleviates the inflammatory response of acute gouty arthritis by inhibiting of IL-1β / 细胞与分子免疫学杂志

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.

O-arm navigation versus C-arm navigation for guiding percutaneous long sacroiliac screws placement in treatment of Denis type Ⅱ sacral fractures / 中国修复重建外科杂志

OBJECTIVE@#To compare the effectiveness of O-arm navigation and C-arm navigation for guiding percutaneous long sacroiliac screws in treatment of Denis type Ⅱ sacral fractures.@*METHODS@#A retrospective study was conducted on clinical data of the 46 patients with Denis type Ⅱ sacral fractures between April 2021 and October 2022. Among them, 19 patients underwent O-arm navigation assisted percutaneous long sacroiliac screw fixation (O-arm navigation group), and 27 patients underwent C-arm navigation assisted percutaneous long sacroiliac screw fixation (C-arm navigation group). There was no significant difference in gender, age, causes of injuries, Tile classification of pelvic fractures, combined injury, the interval from injury to operation between the two groups ( P>0.05). The intraoperative preparation time, the placement time of each screw, the fluoroscopy time of each screw during placement, screw position accuracy, the quality of fracture reduction, and fracture healing time were recorded and compared, postoperative complications were observed. Pelvic function was evaluated by Majeed score at last follow-up.@*RESULTS@#All operations were completed successfully, and all incisions healed by first intention. Compared to the C-arm navigation group, the O-arm navigation group had shorter intraoperative preparation time, placement time of each screw, and fluoroscopy time, with significant differences ( P<0.05). There was no significant difference in screw position accuracy and the quality of fracture reduction ( P>0.05). There was no nerve or vascular injury during screw placed in the two groups. All patients in both groups were followed up, with the follow-up time of 6-21 months (mean, 12.0 months). Imaging re-examination showed that both groups achieved bony healing, and there was no significant difference in fracture healing time between the two groups ( P>0.05). During follow-up, there was no postoperative complications, such as screw loosening and breaking or loss of fracture reduction. At last follow-up, there was no significant difference in pelvic function between the two groups ( P>0.05).@*CONCLUSION@#Compared with the C-arm navigation, the O-arm navigation assisted percutaneous long sacroiliac screws for the treatment of Denis typeⅡsacral fractures can significantly shorten the intraoperative preparation time, screw placement time, and fluoroscopy time, improve the accuracy of screw placement, and obtain clearer navigation images.

Laparoscopic surgery contributes to a decrease in short-term complications in surgical ulcerative colitis patients during 2008–2017: a multicenter retrospective study in China

Background/Aims@#The aim of this study was to analyze the chronological changes in postoperative complications in surgical ulcerative colitis patients over the past decade in China and to investigate the potential parameters that contributed to the changes. @*Methods@#Ulcerative colitis patients who underwent surgery during 2008–2017 were retrospectively enrolled from 13 hospitals in China. Postoperative complications were compared among different operation years. Risk factors for complications were identified by logistic regression analysis. @*Results@#A total of 446 surgical ulcerative colitis patients were analyzed. Fewer short-term complications (24.8% vs. 41.0%, P=0.001) and more laparoscopic surgeries (66.4% vs. 25.0%, P<0.001) were found among patients who received surgery during 2014–2017 than 2008–2013. Logistic regression suggested that independent protective factors against short-term complications were a higher preoperative body mass index (odds ratio [OR], 0.870; 95% confidence interval [CI], 0.785–0.964; P=0.008), laparoscopic surgery (OR, 0.391; 95% CI, 0.217–0.705; P=0.002) and elective surgery (OR, 0.213; 95% CI, 0.067–0.675; P=0.009). The chronological decrease in short-term complications was associated with an increase in laparoscopic surgery. @*Conclusions@#Our data revealed a downward trend of short-term postoperative complications among surgical ulcerative colitis patients in China during the past decade, which may be due to the promotion of minimally invasive techniques among Chinese surgeons.

Evaluation of the efficiency of medical resource utilization in public traditional Chinese medicine hospitals in Gansu province / 中华医院管理杂志

Objective:To analyze the efficiency of medical resource utilization in public traditional Chinese medicine (TCM) hospitals in Gansu province from 2016 to 2020, so as to provide decision-making reference.Methods:The number of in-service staff, actual number of open beds, number of diagnosis and treatment, and number of discharge from TCM hospitals in Gansu province from 2016 to 2020 were extracted, and their technical efficiency, pure technical efficiency, scale efficiency, and returns to scale were analyzed by data envelopment analysis.Results:From 2016 to 2020, the average technical efficiency, pure technical efficiency, and scale efficiency of the sample hospitals were 0.647, 0.680, and 0.952, respectively. Among them, 213 hospitals (48.2%) were in a decreasing state of returns to scale, 54 hospitals (12.2%) were in a constant state of returns to scale, and 175 hospitals (39.6%) were in an increasing state of returns to scale; Out of the 45 tertiary hospitals, 42 (93.3%) were in the stage of diminishing returns to scale, while 226 (56.9%) of 397 secondary and lower hospitals were in a state of constant or increasing returns to scale.Conclusions:The utilization efficiency of medical resources in public TCM hospitals in Gansu province is relatively low, and there is a significant gap between different levels of TCM hospitals.

Application of artificial intelligence intestinal sound monitoring in the decision of postoperative feeding time in Crohn's patients / 中华普通外科杂志

Objective:To evaluate the impact of artificial intelligence continuous bowel sound auscultation recorder on enhanced recovery after surgery for patients with Crohn's disease.Methods:60 patients with Crohn's disease who underwent surgery in Sir Run Run Shaw Hospital , Zhejiang University School of Medicine in 2021 were enrolled in this trial prospectively. They were rendered to oral nutritional supplements (ONS) after surgery according to the hint given by artificial intelligence continuous bowel sound auscultation recorder or doctor's experience. In order to investigate the clinical value of artificial intelligence continuous bowel sound auscultation recorder.Results:the first postoperative flatus was earlier in the intervention group compared with control group [(58.3±1.5) h vs. (63.5±1.2) h, t=3.025, P=0.036], and the first ONS time was (18.3±0.3) h vs. (22.1±0.7) h, t=3.521, P=0.026; the incidence of postoperative complications in the intervention group was lower than that in the control group (3% vs. 7%, t=1.954, P=0.048) and the postoperative hospital stay was shorter [(7.2±0.4) d vs. (8.5±0.4) d, t=2.954, P=0.030]. The incidence of postoperative abdominal pain, abdominal distension, nausea, vomiting and fatigue in the intervention group was slightly lower than that in the control group, without statistically significant difference. Conclusion:In patient with Crohn's disease, the artificial intelligence continuous bowel sound auscultation recorder picks up accurate postoperative exhaust time, indicates the time of fist ONS after surgery, and shorten the postoperative hospital stay, without increase postoperative complication such as abdominal pain distension, accelerates postoperative recovery.

Correlation study on mesenteric fat and disease behavior in patients of Crohn's disease / 中华普通外科杂志

Objective:To analyze the relationship between mesenteric fat or creeping fat and bowel stricture or penetrating disease of Crohn's disease (CD).Methods:Clinical data of 101 CD patients undergoing bowel surgery at Department of General Surgery in our hospital between Mar 2021 and Dec 2021 were retrospectively analyzed. The characteristics of mesenteric fat, creeping fat, luminal cross-section diameter, and the intestinal stricture index were analyzed. The Spearman correlation analysis was used to evaluate the correlation between disease behavior and mesenteric fat score or creeping fat score.Results:Totally 101 CD patients were enrolled, with 68 stricturing diseases and 33 penetrating diseases. CD patients with stricturing diseases had higher score of mesenteric disease activity index (4.6±1.9 vs. 3.7±2.0, t=2.212, P=0.029) and creeping fat index (4.2±2.0 vs. 2.9±1.6, t=3.154, P=0.002) than those in patients with penetrating diseases. The mesenteric fat and creeping fat score positively correlated with the intestinal stricture index, C-reactive protein, and fecal calprotectin, and negatively correlated with minimum luminal cross-section diameter. Conclusion:The higher score of mesenteric fat and creeping fat were observed in CD patients with stricturing disease, which were associated with intestinal stricture index and inflammation status.

Optimization efficacy of individualized LPVS based on P-V curve combined with PCV-VG mode for OLV in elderly patients undergoing radical resection of lung cancer / 中华麻醉学杂志

Objective:To evaluate the optimization efficacy of pressure-volume (P-V) curve-based individualized lung-protective ventilation strategy combined with pressure-controlled ventilation-volume guaranteed (PCV-VG) mode (LPVS+ PCV-VG) for one-lung ventilation (OLV) in elderly patients undergoing radical resection of lung cancer.Methods:Seventy American Society of Anesthesiologists Physical Status classificationⅡ-Ⅲ patients, aged 65-74 yr, with body mass index of 18-24 kg/m 2, undergoing elective thoracoscopic radical resection of lung cancer, were divided into 2 groups ( n=35 each) using a random number table method: PCV-VG group and LPVS+ PCV-VG group. Blood samples were collected from the radial artery for blood gas analysis before induction of general anesthesia (T 0), at 5 min of two lung ventilation after endotracheal intubation (T 1), at 30 min of OLV (T 2), at the end of OLV (T 3), and at 5 min of two lung ventilation in supine position (T 4). Ppeak, mean airway pressure (Pmean) and dynamic lung compliance (Cdyn) were recorded. The use of antibiotics, lung-related complications and rehabilitation were recorded within 7 days after operation. Results:Compared with PCV-VG group, PaO 2, PaCO 2 and Cdyn were significantly increased at T 2-4, Ppeak was decreased at T 2, 3, Pmean was increased at T 3, the requirement for antibiotics within 7 days after operation was decreased, the incidence of 1 grade lung-related complications was decreased, and the thoracic drainage tube indwelling time and length of hospital stay were shortened in LPVS+ PCV-VG group ( P<0.05). Conclusions:Individualized LPVS based on P-V curve combined with PCV-VG mode provides better efficacy for OLV in elderly patients undergoing radical resection of lung cancer.

Relationship between cardiometabolic index and hyperuricemia in health examination population / 中华健康管理学杂志

Objective:To investigate the relationship between cardiometabolic index (CMI) and hyperuricemia (HUA) in the health examination population.Methods:It was a cross-sectional study. A total of 21 720 individuals who received health examinations in Xiangya hospital, Central South University between 2020 and 2021 were recruited in this study. Multivariate logistic regression analysis was used to determine the independent correlation between CMI and HUA, and stratified analysis was applied to check whether there were population differences. Then the predictive value of CMI for hyperuricemia in the health examination population was evaluated with the area under the receiver operator characteristic (ROC) curve.Results:Among the 21 720 subjects, 4 418 (20.34%) were detected with HUA. In the HUA group, the body mass index (BMI), waist-to-hip ratio, CMI, total cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, fasting blood glucose, 2-hour postprandial blood glucose, and blood creatinine levels were all significantly higher than those in the normal uric acid group, while high-density lipoprotein and epidermal growth factor receptor (eGFR) were significantly lower (all P<0.05). Multiple logistic regression analysis showed that after adjusting for relevant factors, CMI was significantly positively correlated with HUA ( OR=1.16, 95% CI: 1.129-1.192); and with the increase of CMI, the risk of HUA increased gradually. Stratified analysis and interaction test according to gender, age, BMI, hypertension, abnormal blood glucose and glomerular filtration rate indicated that CMI was positively associated with the occurrence of HUA in all populations. Compared with that in people with abnormal blood glucose, the correlation between CMI and HUA was more obvious in people with normal blood glucose. The area under the ROC curve (AUC) for CMI to predict HUA was 0.723(95% CI: 0.715-0.731), with a specificity of 0.636 and a sensitivity of 0.698, and the cut-point was 0.693. Conclusion:There was a significant positive correlation between CMI and HUA in the health examination population, which has good predictive value for HUA.

Correlation between lipid accumulation index and hyperuricemia in health examination population / 中华健康管理学杂志

Objective:To understand the relationship between lipid accumulation product (LAP) and hyperuricemia in physical examination population.Methods:This was a cross-sectional study. The analysis was based on baseline data from a retrospective cohort study. Total of 44 294 people who received physical examination in the Health Management Center of Xiangya Hospital of Central South University from January to December 2012 were selected as subjects with whole-group sampling method. All the subjects aged ≥18 years with complete study variables. The minimum waist circumference of the subjects was calculated to determine the criteria for calculating LAP in those population. With LAP as the observed variable and hyperuricemia as the outcome variable, LAP was divided into four groups according to the interquartile interval (Q 1-Q 4 groups): group Q 1<10.56 cm·mmol/L, 10.56 cm·mmol/L≤Q 2<20.79 cm·mmol/L, 20.79 cm·mmol/L≤Q 3<38.94 cm·mmol/L, Q 4≥38.94 cm·mmol/L. Five models were constructed with logistic regression analysis. No confounding factors was adjusted in Model 1, model 2 was adjusted for age and gender; and model 3 was further adjusted for body mass index, hypertension, hyperlipidemia, creatinine and glomerular filtration rate; model 4 was further adjusted education level, occupation, health insurance, smoking, drinking, diet scores and physical exercise; model 5 was further adjusted the family history of gout, diabetes and hypertension. And the relationship between different LAP levels and hyperuricemia was analyzed. Results:In this study, the minimum waist circumference in the physical examination population was 58 cm and 53 cm for men and women, respectively. The total incidence of hyperuricemia was 13.4% in this population, 5.94% for women and 19.40% for men. When the confounding factors were not adjusted (model 1), the risk of hyperuricemia in women′s LAP Q 2 to Q 4 groups was 1.76 times (95% CI: 1.42-2.17), 5.08 times (95% CI: 4.20-6.14) and 12.58 times (95% CI: 10.43-15.18), and it was 1.68 times (95% CI: 1.43-1.96), 2.74 times (95% CI: 2.36-3.18), and 5.32 times (95% CI: 4.62-6.14) in men, respectively. After gender stratification and adjustment for confounding factors (model 5), the risk still existed, compared with that in Q 1 group of LAP, the risk of hyperuricemia in women in Q 4 group was 8.28 times higher (95% CI: 2.50-27.38) and 3.31 times higher in men (95% CI: 1.57-6.95). Conclusion:The risk of hyperuricemia in health examination population increases with LAP, especially in women.

Study of molecular markers of plasma exosomal proteins in patients with spinal cord injury / 中华骨科杂志

Objective:To screen plasma exosomal protein molecular markers in patients with spinal cord injury (SCI) by applying Label-Free quantification and bioinformatics analysis.Methods:Fifty plasma specimens from the First Affiliated Hospital of Nanjing Medical University (from January 2021 to June 2022) were collected from SCI patients and healthy people, respectively. Plasma exosomes were isolated using ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blot. Plasma exosomal differentially expressed proteins (DEPs) were analyzed using Label-Free quantitative proteomics, and DEPs were characterized, annotated, and enriched based on Gene Ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) databases. The screened DEPs were validated by western blot and enzyme linked immunosorbent assay (ELISA) using plasma exosomal specimens.Results:According to the spinal cord injury classification of the American Spinal Injury Association, 14 cases were grade A, 19 cases were grade B, 12 cases were grade C, and 5 cases were grade D. Plasma exosomes of SCI patients and control groups showed typical cup-like morphology, with diameters mainly ranging from 30-200 nm. A total of 493 exosomal proteins were identified by Label-Free quantification, and 126 proteins were screened for differential expression, of which 38 were up-regulated and 88 were down-regulated. GO annotation revealed that DEPs were mainly involved in functions such as protein activation cascade, complement activation and immune response. KEGG pathway analysis revealed that DEPs were involved in biological pathways such as complement and coagulation cascade reactions, proteasome and neurodegenerative disease pathways. Two candidate proteins, APOB and S100A9, were initially screened based on quantitative results from proteomics and bioinformatics analyses. Western blot results showed that the relative expression of S100A9 protein in plasma exosomes of 30 SCI patients (1.62±0.19) was elevated compared with that of 30 control groups (0.86±0.24), and the difference was statistically significant ( t=8.55, P<0.001), while the relative expression of APOB protein (1.06±0.13 and 1.02±0.23) were not statistically significant ( t=0.46, P=0.653). The results of ELISA analysis showed that the expression of S100A9 in plasma exosomes of patients with different degrees of SCI (grade A 197.7±11.7 pg/ml, grade B 151.7±15.2 pg/ml, grade C 136.3±14.7 pg/ml) had statistical significance ( F=69.94, P<0.001), the higher the severity of SCI, the higher the expression of S100A9 in plasma exosomes (A vs. B, q=13.11, P<0.001; A vs. C, q=15.66, P<0.001; B vs. C, q=4.19, P=0.005). Conclusion:S100A9 is a potentially valid plasma exosomal molecular marker for assessing the severity of SCI.

Radiation dose and fractionation regimen for limited stage small cell lung cancer: a survey of current practice patterns of Chinese radiation oncologists / 中华放射肿瘤学杂志

Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.

Inosine:A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation / 药物分析学报

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19(COVID-19)progression,severity,criticality,and death.Gluco-corticoid and anti-cytokine therapies are frequently administered to treat COVID-19,but have limited clinical efficacy in severe and critical cases.Nevertheless,the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection.We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin(IL)-6,upregulated anti-inflammatory IL-10,and ameliorated acute inflammatory lung injury caused by mul-tiple infectious agents.Inosine significantly improved survival in mice infected with SARS-CoV-2.It indirectly impeded TANK-binding kinase 1(TBK1)phosphorylation by binding stimulator of interferon genes(STING)and glycogen synthase kinase-3β(GSK3β),inhibited the activation and nuclear trans-location of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopoly-saccharide(LPS),H1N1,or SARS-CoV-2.Thus,inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19.Moreover,targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

Efficacy and safety of Omalizumab for the treatment of pediatric allergic asthma: a retrospective multicenter real-world study in China / 中华实用儿科临床杂志

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Biomechanical Study on Contiguous Three-Level Cervical Hybrid Surgery and Anterior Cervical Discectomy and Fusion / 医用生物力学

Objective To compare the biomechanical effects of contiguous three-level cervical Hybrid surgery[anterior cervical discectomy and fusion (ACDF) + cervical disc arthroplasty ( CDA)] and three-level ACDF. Methods The finite element model of C1-T1 cervical-thoracic spine was developed based on CT data. Three models were simulated by the implantation of Prestige LP and Zero-P prostheses, including two Hybrid models (AFA, Prestige LP implanted at C3-4 and C5-6 segments and Zero-P implanted at C4-5 segment; FAF, Zero-P implanted at C3-4 and C5-6 segments and Prestige LP implanted at C4-5 segment) and three-level ACDF model(FFF). The changes in range of motion (ROM) of adjacent levels during flexion, extension, lateral bending and axial rotation, the overall ROM, as well as the intradiscal pressure ( IDP) and facet contact force ( FCF) of adjacent levels were compared. Results The ROM in adjacent levels and the overall ROM of the AFA modelwere closer to the intact model, and the maximum increases in the ROM of the adjacent levels for the FAF and FFF models were 15. 0% and 23. 4% , respectively. For AFA, FAF and FFF models, the maximum increases in the maximum IDP of adjacent levels were 19. 0% , 66. 7% , 147. 6% , and the maximum increases in FCF were 17. 4% , 55. 7% , 80. 1% , respectively. Conclusions This study provides biomechanical basis for three-level cervical Hybrid surgery in treating patients with the contiguous three-level cervical degenerative disc disease.

Discussion on safety and related pharmacological mechanism of compound anshen essential oil in relieving sleep disorders / 中国药理学通报

Aim To study the hypnotic effect and safety of compound anshen essential oil. Methods Gas chromatograph-mass spectrometer (GC-MS) was used to analyze the main active components of compound anshen essential oil. The mouse model of insomnia was established by intraperitoneal injection of para-chloro-phenyl alanine ( PC PA ) , combined with pentobarbital sodium sleep experiment and EEG characteristic monitoring in rats to study the hypnotic effect and mechanism. The safety of compound anshen essential oil was evaluated by acute toxicity test, skin irritation/allergy test and 90-day repeated administration toxicity test. The clinical effect and safety were evaluated by using the sleep monitoring technology for micro-motion sensitive mattress. Results Four components, including Atractylone (34.61%), (+) -Limonene (17.80%) , Linalool (11.63%), and Ocimene (11.67%) , were detected as the main active components of compound anshen essential oil. Compound anshen essential oil in-halation administration for seven days could effectively reduce the autonomic activity of insomnia mice, shorten the sleep latency (P <0.05) , improve the sleep duration, increase of neurotransmitters such as 5-hydroxy tryptamine (5-HT) and -γ-aminobutyric acid (GABA) in brain of mice with insomnia, and the medium dose group had better hypnotic effect. There was no death or adverse reaction in the safety evaluation test. The sleep balance index of 10 subjects with difficulty in falling a-sleep significantly increased (P <0.05), sleep latency was significantly shortened (P <0.05) , total sleep duration and sleep efficiency were improved, and no ad¬verse reactions were found after using the compound anshen essential oil for two days. Conclusions The compound anshen essential oil developed by the research team is safe and effective in relieving sleep disorders, which may be closely related to the co-regulation of the levels of neurotransmitters such as 5-HT and GABA by the four main active components.

Mechanism study of Dangshen Pingfei Huoxue decoction in treatment of pulmonary fibrosis based on network pharmacology and molecular docking / 中国药理学通报

Aim To explore the potential mechanism of Dangshen Pingfei Huoxue decoction (DPHD) in the treatment of pulmonary fibrosis. Methods The common targets of DPHD and pulmonary fibrosis were obtained. Cytoscape software was used to construct " disease-drug-ingredients-targets " network diagram, and the common targets were imported into the STRING database for protein-protein interaction (PPI) analysis to screen out the core targets. In order to screen out key signaling pathways, the core genes were inputted into the DAVID platform for gene ontology (GO) and kyoto encyclopedia of genes genomes (KEGG) enrichment analysis. Then the molecular docking technology was used to verify the molecular docking between the core components and the key proteins in the signaling pathway. Finally, the molecular docking technology was used to verify the results of network pharmacology. Results A total of 176 active ingredients were obtained, and the top 5 was quercetin, kaempferol, luteolin, naringenin and p-sitosterol, respectively. A total of 116 common targets were obtained. A total of 21 core targets were finally obtained by PPI screening, and the top 5 was AKT1, CCND1, CASP3, MYC and IL1B, respectively. The results of GO enrichment analysis showed that DPHD was mainly involved biological processes of oxidative stress, proliferation and differentiation, transcriptional regulation, drug response and inflammatory response. The results of KEGG enrichment analysis indicated that the mainly signaling pathways included PI3K/Akt, MAPK, cellular senescence, AMPK, and TGF-beta. Molecular docking results showed that the binding energies of the top 5 active components of DPHD and the top 5 core targets were all less than-6.0 kcal • mo

Analysis on the spectrum characteristics of noise hazards in metal products industry / 中国职业医学

{L-End}Objective To analyze the spectrum characteristics of noise hazards in the metal products industry. {L-End}Methods A total of six metal product industries were selected as research subjects using stratified sampling method. The noise intensity (A/C-weighted) and noise spectrum (Z-weighted) of workplaces and job positions were detected. The characteristics of the noise spectrum of each job position were analyzed using the difference between equivalent continuous C-weighted sound pressure level (LCeq)-equivalent continuous A-weighted sound pressure level (LAeq), the dominant frequency of the noise spectrum, and cluster analysis methods. {L-End}Results The workplace noise and job position noise of 11 main noise positions in the metal products industry were exceeded national standard, with incidence of 69.2% and 78.1%, respectively. The average of normalization of equivalent continuous A-weighted sound pressure level to a normal 40 hours working week exceeded the national standard in 100.0% of hydraulic workers, welders, and ultrasonic cleaning workers. The result of spectrum analysis showed that the noise in the metal product industry was mainly broadband. The noise of the collision welder position was classified as low-frequency broadband noise, while the noise of the painter position was classified as low-frequency narrowband noise. The noise spectrum characteristics of other positions were similar and classified into one category, all of which were broadband noise. Among them, numerical control lathe workers, welders, threaders, machinists, and cutters were exposed to high-frequency broadband noise, while press workers were exposed to mid-frequency broadband noise, and grinders, hydraulic workers, and ultrasonic cleaning workers were exposed to low-frequency broadband noise. The detection rate of binaural high-frequency hearing threshold improvement among workers was 61.7%, and there was no statistical correlation between the detection rate of binaural high-frequency hearing threshold improvement and the noise level intensity of each spectrum. {L-End}Conclusion The level of noise hazards in the metal products industry is severe. Effective engineering control measures and hearing protection measures should be implemented based on the spectral characteristics of noises.