Progress of early warning indicators on infectious diseases / 上海预防医学

In recent years， with frequent outbreaks of infectious diseases around the world， the global public health is faced with many threats and challenges. An infectious diseases early warning system is an important means for prevention and control of infectious diseases. As an important part of the early warning system， the warning indicators is crucial for understanding the occurrence and development trend of infectious diseases， detecting abnormal situations timely and effectively， and issuing early warning and initiating emergency response. Based on the occurrence and development process of infectious diseases， this paper summarizes the research status of early warning indicators on infectious diseases， in order to provide reference for the development and improvement of the infectious diseases early warning system.

Establishment and application of a prospective follow-up research method for acute infectious diseases in Shanghai community residents / 上海预防医学

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system. MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described. ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections. ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Longitudinal association between processed food consumption and anxiety symptoms among college students in Yunnan Province / 中国学校卫生

Objective@#To explore the association between processed food consumption and anxiety symptoms among college students in Yunnan Province, so as to provide a reference for the prevention and treatment of anxiety symptoms in this population.@*Methods@#A cluster random sample of 2 515 first year students from two universities in Yunnan Province was selected to carry out a longitudinal investigation which included a baseline survey (November 2021, T1) and three follow up visits (June 2022, T2; November 2022, T3; June 2023, T4). The food frequency questionnaire was administered to assess processed food consumption, and the Depression Anxiety Stress Scale-21 (DASS-21, Chinese version) was used to evaluate anxiety symptoms. A generalized estimation equation model was used to analyze the relationship between processed food consumption and anxiety symptoms.@*Results@#The detection rates of T1-T4 anxiety symptoms among college students in Yunnan Province were 29.70%, 36.70%, 37.69% and 38.73 %, respectively, and the corresponding anxiety symptom scores were 4(0,8), 4(0,10), 4(0,12), 2(0,14). After controlling for demographic variables and confounding factors in the generalized estimation equation model, a statistically significant association was found between consumption of carbonated beverages ( β=0.06, 95%CI =0.03-0.08), and other processed snacks ( β= 0.04 , 95%CI =0.01-0.07) ( P <0.05). The stratified analysis by gender showed that the consumption of carbonated beverages ( β=0.08, 95%CI =0.05-0.12) and fast food ( β=0.03, 95%CI =0.00-0.06) was significantly associated with anxiety symptoms in female college students ( P <0.05). There was no significant association between processed food consumption and anxiety symptoms in male college students ( P >0.05).@*Conclusions@#Processed food consumption by college students in Yunnan Province may increase the risk of anxiety symptoms, particularly among female students. There is a need to strengthen guidance in respect to processed food consumption, so as to prevent and treat anxiety symptoms.

Development of biosensors highly responsive to N-acetylneuraminic acid in Bacillus subtilis / 生物工程学报

Bacillus subtilis is recognized as a generally-regarded-as-safe strain, and has been widely used in the biosynthesis of high value-added products, including N-acetylneuraminic acid (NeuAc) which is widely used as a nutraceutical and a pharmaceutical intermediate. Biosensors responding to target products are widely used in dynamic regulation and high-throughput screening in metabolic engineering to improve the efficiency of biosynthesis. However, B. subtilis lacks biosensors that can efficiently respond to NeuAc. This study first tested and optimized the transport capacity of NeuAc transporters, and obtained a series of strains with different transport capacities for testing NeuAc-responsive biosensors. Subsequently, the binding site sequence of Bbr_NanR responding to NeuAc was inserted into different sites of the constitutive promoter of B. subtilis, and active hybrid promoters were obtained. Next, by introducing and optimizing the expression of Bbr_NanR in B. subtilis with NeuAc transport capacity, we obtained an NeuAc-responsive biosensor with wide dynamic range and higher activation fold. Among them, P535-N2 can sensitively respond to changes in intracellular NeuAc concentration, with the largest dynamic range (180-20 245) AU/OD. P566-N2 shows a 122-fold of activation, which is 2 times of the reported NeuAc-responsive biosensor in B. subtilis. The NeuAc-responsive biosensor developed in this study can be used to screen enzyme mutants and B. subtilis strains with high NeuAc production efficiency, providing an efficient and sensitive analysis and regulation tool for biosynthesis of NeuAc in B. subtilis.

Prevalence of respiratory and allergic diseases in children in Xuhui District， Shanghai in 2013 and 2020 / 上海预防医学

ObjectiveTo compare the incidence of respiratory and allergic diseases in children in Xuhui District， Shanghai in 2013 and 2020， and to determine the influencing factors. MethodsAnnual average levels of air pollutants including PM2.5， PM10， O3， SO2， and NO2 were collected and described in Shanghai from 2013 to 2020. A cross-sectional survey was conducted by using a questionnaire among grade 3 to 5 students in a school in Xuhui District， Shanghai， in September 2013 and 2020， respectively. The questionnaire collected variables including living environment， daily habits， family history of respiratory and allergic diseases， and incidence of these diseases in children. Chi-square test was used to determine the difference across respiratory and allergic diseases. Logistic regression was conducted to determine the influencing factors. ResultsA total of 1 398 valid questionnaires were collected （705 in 2013 and 693 in 2020）. Compared with 2013， annual average concentrations of PM2.5， PM10， O3， SO2， and NO2 in 2020 significantly decreased. The prevalence of bronchial asthma， bronchitis， persistent cough and persistent expectoration in 2013 were significantly higher than those in 2020 （P<0.05） in Xuhui District. Multivariate analysis showed that severe air pollution， boys， parents with asthma or allergy， parents with higher educational levels， and more allergens in household were the risk factors associated with the incidence of bronchial asthma， bronchitis， allergic rhinitis and atopic eczema （P<0.05）. Parents with allergy history， high smoking frequency of family member， and more allergens in household were the risk factors associated with the incidence of persistent cough and persistent expectoration （P<0.05）. ConclusionTo 2013，2020 air pollution in Shanghai has been mitigated and prevalence of bronchial asthma and bronchitis of children has decreased. Childhood respiratory and allergic diseases are associated with indoor and outdoor environment， family medical history， and family daily habits.

To explore the quality markers of Huangqin Qingre Chubi capsule in the treatment of rheumatoid arthritis based on network pharmacology combined with pharmacokinetics and target verification / 药学学报

As an effective prescription for the treatment of rheumatoid arthritis (RA), Huangqin Qingre Chubi capsule (HQC) is still blank in quality control. This study aims to explore quality markers (Q-markers) for HQC in the treatment of RA by integrating network pharmacology and pharmacokinetics. By constructing the visualization network of "pharmacodynamic ingredient-target-pathway", the potential Q-Marker of HQC treatment for RA was preliminatively predicted. A rat model of rheumatic heat obstruction syndrome collagene-induced arthritis (CIA) was established to elucidate the dynamic quantification law of pharmacodynamic components of HQC in the disease state of rats. To establish the inflammatory model of RA synovial fibroblasts (MH7A) induced by tumor necrosis factor-α (TNF-α) in vitro. The effects of active ingredients on protein expression of sphingosin kinase-1 (Sphk1) and p-SphK1 were detected. The network pharmacological results showed that baicalin, geniposide, luteolin, coixol and amygdalin were the important active components of HQC treatment for RA. Quantitative analysis results further verified the measurability of these five components. The expression of Sphk1 and p-SphK1 was significantly inhibited by geniposide and baicalin by Western blotting. The above studies determined that the above 5 components could be used as Q-markers in the treatment of RA by HQC. This experiment was approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). All procedures were conducted in strict accordance with the principles of animal use and care.

Effects of titanium dioxide nanoparticles on circRNA expression profiles in human hepatocellular carcinoma cells HepG2 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of titanium dioxide nanoparticles (TiO2 NPs) on the expression profile of circular ribonucleic acid (circRNA) in human hepatocytes through in vitro cell experiments, and to attempt to understand the potential mechanism of hepatotoxicity through bioinformatics analysis.@*METHODS@#TiO2 NPs were characterized from the aspects of particle size, shape and agglomeration state. The cell counting kit-8 (CCK8) was used to detect the cytotoxicity of TiO2 NPs against human hepatocellular carcinoma cells (HepG2) after exposure to 0, 1.56, 3.13, 6.25, 12.5, 25, 50, 100, and 200 mg/L TiO2 NPs for 24 h or 48 h. The cells were treated at doses of 0 mg/L TiO2 NPs (control group) and 100 mg/L TiO2 NPs (treatment group), and collected after exposure for 48 h, and then RNA from the extracted cell samples was collected and sequenced. The differential circRNAs between the control and the TiO2 NPs treatment groups were screened, and then the enrichment pathway of the differential circRNA target gene was analyzed by multivariate statistics. According to the sequencing results, significantly altered genes and important genes in the significant enrichment pathways were screened, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) was performed to verify the results.@*RESULTS@#TiO2 NPs were spherical anatase with a hydrated particle size of (323.50±85.44) nm and a Zeta potential of (-21.00±0.72) mV in a serum-free medium. The results of the CCK8 cytotoxicity assay showed that with the increase of TiO2 NPs concentration, cell viability gradually decreased. A total of 11 478 circRNAs were found by RNA sequencing. Compared with the control groups, TiO2 NPs treatment groups (100 mg/L) had a total of 89 differential circRNAs, of which 59 were up-regulated and 30 were down-regulated. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the targeted genes of differential circRNAs were mainly enriched in fatty acid degradation, Fanconi anemia pathway, and fatty acid metabolism. The expression levels of circRNA.6730, circRNA.3650 and circRNA.4321 were significantly different between the TiO2 NPs treatment group and the control group, which were consistent with the sequencing results.@*CONCLUSION@#TiO2 NPs can induce changes in circRNA expression profile, and epigenetics may play an important role in the mechanism of hepatotoxicity.

Pharmacokinetics of Recombinant Human Coagulation Factor Ⅷ Preparations in Patients with Severe Hemophilia A / 中国实验血液学杂志

OBJECTIVE@#To calculate the pharmacokinetic parameters of recombinant human coagulation factor Ⅷ using myPKFiT in patients with severe hemophilia A, and provide an individualized treatment plan for patients.@*METHODS@#A total of 42 patients with severe hemophilia A who were treated with recombinant human coagulation factor Ⅷ were included from January 2021 to December 2021. myPKFiT was used to calculate the pharmacokinetic parameters of FⅧ, and the individualized treatment plan for hemophilia A patients was formulated.@*RESULTS@#The median age of 42 patients with severe hemophilia A was 31（16-50） years old, the average weight was 54.0±9.9 kg, the half-life of FⅧ was 12.05±1.6 h, the time to more than 1% of the baseline was 62.3±15.3 h, and the 0 bleeding rate after the guidance of myPKFiT was significantly increased from 39% to 49%, the Annual bleeding rate was reduced from 3.6±2.5 to 2.1±2.0, and the Annual joint bleeding rate was reduced from 3.2±2.2 to 1.9±0.9, all of which were statistically different (P<0.05).@*CONCLUSION@#Individualized therapy in patients with severe hemophilia A who were guided by myPKFiT assay of pharmacokinetics parameters can significantly reduce the annual bleeding rate and annual joint bleeding rate of patients.

Expression and significance of jumonji domain-containing protein 2B and hypoxia inducible factor-1α in non-Hodgkin lymphoma tissues in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children.@*METHODS@#Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed.@*RESULTS@#The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024).@*CONCLUSIONS@#JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.

Arthroscopic assistance of latissimus dorsi tendon transposition for the treatment of unrepairable rotator cuff tear / 中国骨伤

OBJECTIVE@#To explore clinical effect of arthroscopy-assisted rotator cuff tendon transfer in treating irreparable rotator cuff tears (IRCT).@*METHODS@#From May 2015 to May 2018, 23 patients with unrepairable rotator cuff tears were treated with arthroscopy-assisted rotator cuff tendon transfer, and 21 patients were followed up finally, including 8 males and 13 females, aged from 48 to 82 years old with an average of(64.3±9.1) years old;the courses of disease ranged from 6 to 36 months with an average of (14.0±6.4) months. American Rotator and Elbow Surgeons Score(ASES) and Constant-Murley score were used to evaluate clinical efficacy before surgery and at the latest follow-up.@*RESULTS@#All 21 patients were followed up for 36 to 54 months with an average of (39.4±4.4) months. Axillary incision of 1 patient was redness, swelling and exudation after surgery, which healed after 3 weeks of dressing change, and exudate culture was negative. At the latest follow-up, MRI showed partial tearing of the metastatic tendon in 2 patients, but pain and movement of the affected shoulder were still better than before surgery. ASES increased from preoperative (41.0±9.6) scores to the latest follow-up (75.6±14.0) scores, and had statistical difference (t=10.50, P<0.01). Constant-Murley score increased from (49.8±7.1) scores before operation to (67.5±11.6) scores at the latest follow-up (t=11.27, P<0.01).@*CONCLUSION@#Arthroscopic assisted latissimus dorsalis tendon transposition restores physiological and anatomical structure of glenohumeral joint by reconstructing balance of horizontal and vertical couples of shoulder joint, thus achieving the stability of the shoulder joint, relieving shoulder pain and improving shoulder joint function.

Relationship between intramuscular fat content in the quadriceps muscle and clinical severity in patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To explore relationship between intramuscular fat content of quadriceps femoris and clinical severity of knee osteoarthritis (KOA).@*METHODS@#Totally 30 KOA patients were selected from February 2021 to June 2021, including 6 males and 24 females, aged with an average of (64.20±9.19) years old, and body mass index (BMI) was (24.92±3.35) kg·m-2. Patients were divided into relative severe leg (RSL) and relative moderate leg (RML) according to severity of pain on visual analogue scale(VAS). Musculoskeletal ultrasound was used to collect muscle images of quadriceps muscles on both sides of the patient, and Image J was used to analyze echo intensity (EI) of each muscle. Both VAS and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess pain and function. Quadriceps muscle EI on both sides of patients was compared. Pearson correlation analysis was conducted to analyze correlation between quadriceps muscle EI value between RSL and RML, and linear regression was used to analyze relationship between each muscle EI and VAS and WOMA scores of patients.@*RESULTS@#The EI of RSL lateral vastus lateralis (VL) was 123.78±36.25 and RSL vastus medialis (VM) was 109.46±30.36 which were significantly higher than those of 108.03±31.34 and 93.32±26.04 of RML (P<0.05), but there was no statistical significance in EI values of rectus femoris (RF) on both sides (P>0.05). EI values of VL and VM on both sides were significantly correlated (P<0.05). There was a significant positive correlation between VM EI value and VAS score in RSL and RML (P<0.05). VM EI values in RSL were positively correlated with total WOMAC (P<0.05), and VM VL EI values in RML were positively correlated with total WOMAC score (P<0.05).@*CONCLUSION@#Intramuscular fat content of quadriceps is closely related to severity of clinical symptoms in KOA patients, and the most obvious one is VM. Therefore, the intramuscular fat content of quadriceps may be an objective indicator to evaluate severity of KOA patients. At the same time, reducing intramuscular fat content of the quadriceps muscle of KOA patients may be a new direction for the prevention and treatment of KOA.

Difference analysis of 18F-FMISO PET/CT hypoxia imaging in response to heavy ion radiotherapy in patients with non-small cell lung cancer / 中华核医学与分子影像杂志

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.

Basic researches over spinal cord injury: problems and countermeasures / 中华创伤杂志

Spinal cord injury leads to extremely high mortality and disability rates and its treatment has always been a global challenge. The survival of patients with spinal cord injury is partially lengthened with the development of medical treatments, but the clinical outcome is still not satisfactory. Some important progress has been made in the basic researches over spinal cord injury, such as analysis of repair mechanism of spinal cord injury and development of cellular therapies and biological scaffolds of spinal cord injury in China. However, some basic researches show insufficient understanding of the microenvironment and animal model of spinal cord injury and lack support from clinical problems, leading to too simplistic or contradictory conclusions. There is an urgent need to reexamine the research methods and carry out basic and clinical translational researches. Therefore, the authors discuss the key problems and difficulties in basic researches over spinal cord injury and propose improvement suggestions, aiming to provide a reference for conducting basic researches correctly and accelerating clinical innovational transformation.

Features of severe acute respiratory syndrome coronavirus 2 co-infected with other common respiratory pathogens in Shanghai City, 2020-2021 / 中华传染病杂志

Objective:To analyze the features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected with other common respiratory pathogens among coronavirus disease 2019 (COVID-19) patients in Shanghai City, and to provide a reference for scientific prevention and control of COVID-19 and other respiratory infectious diseases.Methods:Descriptive epidemiological approaches were used to analyze the data of COVID-19 reported cases in Shanghai City from January 2020 to February 2021 in the information system of Chinese Disease Prevention and Control. Clinical data of the participants were collected, and their SARS-CoV-2 nucleic acid-positive respiratory specimens were collected at the time of illness onset or admission. Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the 22 respiratory pathogens. Independent-samples t test was used for statistical analysis. Results:Of the 272 patients with COVID-19, 15(5.5%) had co-infection of SARS-CoV-2 with other respiratory pathogens, all of which were double infection. There were three cases infected with enterovirus/rhinovirus, two of each with adenovirus, human metapneumovirus and coronavirus NL63/HKU1, and one of each with coronavirus 229E, influenza A virus H1N1, parainfluenza virus 1 and respiratory syncytial virus B. Two cases infected with Mycoplasma pneumoniae. Among the 272 COVID-19 patients, 212(77.9%) had fever, 117(43.0%) had cough, 46(16.9%) had fatigue, and 35(12.9%) had sore throat. The white blood cell count of co-infection cases was higher than that of non-co-infection cases ((6.8±1.7)×10 9/L vs (5.3±1.6)×10 9/L), and the difference was statistically significant ( t=3.09, P=0.008). Conclusions:There is a certain proportion of co-infection of SARS-CoV-2 with other respiratory pathogens among the COVID-19 cases in Shanghai City, mainly viral pathogens, especially enterovirus/rhinovirus. A rational combination of drugs was recommended to improve the cure rate. Surveillance of acute respiratory infection should be further strengthened as well.

Research Progress of Next Generation Sequencing in Acute Leukemia --Review / 中国实验血液学杂志

With the advent of precision medicine, next-generation sequencing (NGS) is playing an increasingly important role in clinical oncology diagnosis and treatment with its advantages of high sensitivity, high accuracy, high efficiency and operability. NGS reveals the genetic characteristics of acute leukemia(AL) patients by screening for specific disease-causing genes to identify occult as well as complex genetic mutations in patients with AL, leading to early diagnosis and targeted drug therapy for AL patients, as well as to predict disease recurrence by detecting mnimal residual disease (MRD) and analyzing mutated genes to determine patient prognosis. NGS plays an increasingly important role in the diagnosis, treatment and prognosis assessment in AL, providing a direction for the pursuit of precision medicine. This paper reviews the research progress of NGS in AL.

Thoracoscopic combined subsegmentectomy for 76 patients: A retrospective study in a single center / 中国胸心血管外科临床杂志

@#Objective    To summarize the clinical experience of thoracoscopic combined subsegmentectomy (CSS). Methods    The clinical data of 76 patients who underwent thoracoscopic CSS in Anqing Municipal Hospital from May 2018 to July 2022 were retrospectively analyzed, including 22 males and 54 females, aged 27.0-76.0 (54.3±10.5) years. All patients underwent preoperative three-dimensional computed tomography bronchography and angiography using dual source CT. The modified inflation-deflation technique or indocyanine green was used to identify the intersubsegmental border. Results    A total of 86 pulmonary nodules were resected in 76 patients. One patient of left upper lobe S1+2c+S4a, 1 patient of right upper lobe S2b+S3a and 1 patient of right upper lobe S1b+S3b were further performed lobectomy due to insufficient margin. One patient of left upper lobe S1+2+S3a was further performed left upper division segmentectomy due to residual atelectasis. One patient of left upper lobe S1+2c+S3a was further performed left upper division segmentectomy due to B3b+c injury, and the rest completed planned surgeries successfully. The operative time was 90.0-350.0 (174.9±53.2) min. The operative hemorrhage volume was 50.0 (20.0, 50.0) mL. The postoperative hospital stay time was 6.0 (5.0, 7.0) d. Postoperative complications included pulmonary infection in 9 patients, hemoptysis in 3 patients, persistent pulmonary leakage>3 d in 4 patients, pneumothorax in 1 patient, pleural effusion in 1 patient, and myocardial infarction in 1 patient. All of the patients were cured and discharged without perioperative death. Conclusion    Thoracoscopic CSS is relatively complex. Preoperative planning under three-dimensional reconstruction and intraoperative fine operation are helpful for safe completion.

Anthraquinone modifier KA-4c triggers endoplasmic reticulum stress and targets ATF6 against breast cancer cells / 中国药理学通报

Aim To explore the mechanism of the effect of anthraquinone modifier KA-4c on breast cancer cells, and determine its action target by drug affinity reaction target stability technique (DARTS). Methods The cell viability was detected by MTT method. The effect of KA-4c on the morphology of breast cancer cells was studied by HE staining, ER-Tracker Red and electron microscope. The apoptosis rate of breast cancer cells induced by KA-4c was detected by flow cytometry. The expression of apoptotic protein was detected by Western blotting. DARTS and CETSA were used to determine the target of KA-4c. Results KA-4c had the most significant inhibitory effect on the proliferation of triple negative breast cancer MDA-MB231 cells, and could cause endoplasmic reticulum and mitochondrial vacuolation to damage the cells. The apoptosis rate and the expression of apoptosis-related proteins CHOP and caspase-7 increased with the increase of KA-4c concentration. DARTS results showed that KA-4c could activate endoplasmic reticulum protein processing signaling pathway, in which KA-4c bound to ATF6 protein and was resistant to protease hydrolysis. The results of CETSA experiments showed that KA-4c could enhance the expression of ATF6 protein in a concentration-dependent manner. Conclusions KA-4 triggers endoplasmic reticulum stress to induce apoptosis in breast cancer cells. ATF6 may be one of the targets of KA-4c.

Mechanism of pterostilbene reducing oxidative damage in endothelial cells in mouse hepatic sinus / 中国药理学通报

Aim To explore the mechanism of the natural phenolic compound pterostilbene(PTE)in the protection of liver ischemic/reperfusion. Methods A total of 40 C57 mice were divided into control group,model group,drug delivery group and treatment group and a 70% liver ischemic/reperfusion(ischemic 60 min)model was established,then primary LSECs were isolated by perfusion and digestion. Hepatic structural disruption was observed by HE staining. The ultrastructure of hepatic sinus endothelial cells was observed by transmission electron microscopy(TEM). The structure of LSECs fenestrae was observed by scanning electron microscopy(SEM). The expression level of heme oxygenase 1(HO-1)in LSECs was detected by Western blot. Results HE staining showed that PTE protected against hepatic ischemic injury. TEM observed that PTE had a protective effect on hepatic sinus endothelial cells,and the number of LSECs fenestrae in the blank control group was larger and the number of fenestrae in the liver I/R model group was reduced. The number of LSECs fenestrae in the liver I/R model group treated with PTE increased compared with the untreated liver I/R model group. Western blot result showed that PTE was able to induce HO-1 expression in LSECs. Conclusions PTE alleviates oxidative damage of endothelial cells in mouse hepatic sinus by inducing HO-1expression,and protects the liver from ischemia/reperfusion injury.

Survival of Non-small Cell Lung Cancer Patients Treated with Fuzheng Gushe Therapy： A Real World Study / 中国实验方剂学杂志

ObjectiveTo analyze the long-term survival of non-small cell lung cancer （NSCLC） patients treated with Fuzheng Gushe therapy in the real world. MethodA retrospective cohort study was carried out with the NSCLC patients treated with Fuzheng Gushe therapy from January 2014 to December 2018 in Dongzhimen Hospital， Beijing University of Chinese Medicine as the integrated traditional Chinese medicine （TCM） and western medicine cohort. The NSCLC data from January 2011 to December 2015 in the Surveillance， Epidemiology， and End Results （SEER） database were downloaded as the western medicine cohort. The propensity score matching （PSM） was employed to balance the confounding factors between the groups， and comparable samples were obtained from the two groups. The Log-rank test was conducted to compare the overall survival between the groups and the survival curves were established. ResultThe integrated TCM and western medicine cohort and the western medicine cohort included 511 and 5 022 NSCLC patients， respectively. The age， sex， and chemotherapy had no significant differences between the two cohorts， while pathological type， lymph node metastasis （N）， distant metastasis （M）， surgery， and radiotherapy were different between the two cohorts （P<0.05）. After PSM， 122 comparable samples were obtained. The overall survival analysis showed that the total survival of the integrated TCM and western medicine cohort was better than that of the western medicine cohort （P<0.05）. The stratified survival analysis showed that the integrated TCM and western medicine cohort had survival advantages in females， males， the young， and adenocarcinoma， N+， and M+ patients （P<0.05）. ConclusionFuzheng Gushe therapy can significantly improve the overall survival of NSCLC patients， especially in the females， the males， the young， and the patients with adenocarcinoma， lymph node metastasis， and distant metastasis.

Loss of RBFOX2 inhibits meiotic initiation in male mice / 生物工程学报

Meiotic initiation is a critical step in gametogenesis. Recently, some genes required for meiotic initiation have been identified. However, meiosis-initiating factors and the underlying mechanisms are far from being fully understood. We have established a long-term culture system of spermatogonial stem cells (SSCs) and an in vitro model of meiotic initiation using mouse SSCs. Our previous study revealed that the RNA-binding protein RBFOX2 may regulate meiotic initiation, but the role and the mechanism need to be further elucidated. In this study, we constructed RBFOX2 knockdown SSC lines by using lentivirus-mediated gene delivery method, and found that the knockdown SSCs underwent normal self-renewal, mitosis and differentiation. However, they were unable to initiate meiosis when treated with retinoic acid, and they underwent apoptosis. These results indicate that RBFOX2 plays an essential role in meiotic initiation of spermatogonia. This work provides new clues for understanding the functions of RNA-binding proteins in meiotic initiation.