Prognostic Value and Immune Infiltration of Anoikis-related LncRNAs in Lung Adenocarcinoma / 肿瘤防治研究

Objective To explore the prognostic value and immune infiltration landscape of anoikis-related long noncoding RNAs (arlncRNAs) in lung adenocarcinoma. Methods RNA-seq and clinical data of lung adenocarcinoma were downloaded from the TCGA database, and anoikis-related genes were obtained from the GeneCards and Harmonizome databases. Coexpression, differential, and WGCNA analyses were performed to screen differentially expressed arlncRNAs closely related to the occurrence of lung adenocarcinoma. A prognostic risk model was then constructed based on the arlncRNAs, and its predictive efficacy was further validated. Finally, consensus clustering was used to identify the molecular subtypes associated with anoikis in lung adenocarcinoma. Results Seven prognostic arlncRNAs were identified, and the prognostic risk models established based on them had AUC values of ROC curves greater than 0.7. Survival and immune infiltration analyses revealed that low-risk patients had high overall survival and immune infiltration, implying that they experienced good immune treatment effects. Drug sensitivity analysis showed that the high-risk patients were more sensitive to commonly used chemotherapeutic agents than the low-risk patients. According to the expression of model genes, subtypes C1 and C2 were identified through consensus clustering, and C1 showed a good prognosis. Conclusion The prognostic risk model based on the seven arlncRNAs can effectively predict the prognosis of lung adenocarcinoma patients. The results of immune-related and drug sensitivity analyses provide a reference for the precise individualized treatment of patients with lung adenocarcinoma.

Effect of procalcitonin on lipopolysaccharide-induced expression of nucleotide-binding oligomerization domain-like receptor protein 3 and caspase-1 in human umbilical vein endothelial cells / 中国当代儿科杂志

OBJECTIVES@#To study the effect of procalcitonin (PCT) on lipopolysaccharide (LPS)-induced expression of the pyroptosis-related proteins nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and caspase-1 in human umbilical vein endothelial cells (HUVECs).@*METHODS@#HUVECs were induced by LPS to establish a model of sepsis-induced inflammatory endothelial cell injury. The experiment was divided into two parts. In the first part, HUVECs were randomly divided into four groups: normal control, LPS (1 μg/mL), PCT (10 ng/mL), and LPS+PCT (n=3 each). In the second part, HUVECs were randomly grouped: normal control, LPS, and LPS+PCT of different concentrations (0.1, 1, 10, and 100 ng/mL) (n=3 each). Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of NLRP3 and caspase-1 in each group.@*RESULTS@#In the first experiment: compared with the normal control group, the PCT, LPS, and LPS+PCT groups had significantly upregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05); compared with the LPS group, the LPS+PCT group had significantly downregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05). In the second experiment: compared with those in the LPS group, the mRNA and protein expression levels of NLRP3 and caspase-1 in the LPS+PCT of different concentrations groups were significantly downregulated in a concentration-dependent manner (P<0.05).@*CONCLUSIONS@#LPS can promote the expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs, while PCT can inhibit the LPS-induced expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs in a concentration-dependent manner.

The perforator flap of ipsilateral nasolabial sulcus used to repair the defect after the eradication of nasal vestibular squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the feasibility of only surgical resection for nasal vestibular squamous cell carcinoma and the efficacy of perforator flap of ipsilateral nasolabial sulcus in repairing postoperative defects. Methods: The clinical data of 8 cases with squamous cell carcinoma of the nasal vestibule who admitted to Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital, Fudan University were analyzed, including 6 males and 2 females, aged from 38 to 75 years. The tumor of the nasal vestibule was eradicated in time after making definite diagnosis of lesions, then the perforators flap of the ipsilateral nasolabial sulcus was used for repairment, without performing further chemotherapy or radiotherapy after surgery. The tumor recurrence, facial appearance, nostril form, donor area scar, nasal ventilation function, and cutaneous sensation were evaluated after surgery. Descriptive analysis was used in this research. Results: There were 2 cases of stage T1 and 6 cases of stage T2 in 8 cases. After 32 to 45 months of following-up, no recurrence accurred and all the flaps survived well. However, there was about 2 mm necrosis of the transplanted flap in the lateral foot of the alar in one case, which was healed well by carrying out wound care after 10 d. And the dark color flap was occurred in another case, showing the flap's backflow trouble, yet it was improved with addressing timely during 5 d postoperation. Pincusion-like deformity of the transplanted flap occurred in 4 cases (50%), which subsided gradually after 6 months. The morphology of the anterior nostril was altered in 4 cases (50%), but there was no ventilation trouble and no need for addressment in any case. The postoperative facial appearance was rated as excellentor good with hidden scar in the donor site, and the sensation of the transplanted flaps was indistinct from the surrounding tissue after 3 months. Conclusions: Surgical resection of nasal vestibular squamous cell carcinoma with tumor stage T1-2 is a feasible treatment. And it is the one of the best reconstructive methods of the perforator flap of the ipsilateral nasolabial sulcus to repair the deformities after the surgery.

Clinical features and prognostic factors of elderly patients with mantle cell lymphoma / 中华血液学杂志

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

Impact of the interaction between metabolic syndrome and smoking on the risk of cardiovascular events / 中华内分泌代谢杂志

Objective:To investigate the effect of the interaction between metabolic syndrome and smoking on the risk of subsequent cardiovascular events.Methods:Urban residents aged 40 and above in the Yunyan District of Guiyang City were selected from " Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) Study". The baseline survey started in 2011 and general information including gender, age, medical history, lifestyle habits, and smoking status were collected. Additionally, biochemical indicators related to metabolic syndrome(MS) were measured. The study participants were then followed up, and the first cardiovascular events occurring after the initial survey were recorded. The average follow-up period was 10.07±1.49 years. The interaction between metabolic syndrome and smoking on subsequent cardiovascular events was analyzed using Cox proportional hazards models.Results:The study included a total of 7 275 individuals, among whom 639 experienced cardiovascular events. After adjusting for multiple variables, compared to non-smokers without metabolic syndrome(MS), smokers with MS showed a higher risk of cardiovascular events, with a hazard ratio( HR) of 6.54(95% CI 4.88, 8.78). This risk was higher than that of individuals with MS who never smoked [ HR 1.39(95% CI 1.11, 1.75)] and non-MS smokers [ HR 2.48(95% CI 1.77, 3.49)]. There was an additive interaction between MS and smoking on the occurrence of cardiovascular events, with a relative excess risk due to interaction(RERI) of 3.30(95% CI 1.89, 4.70), an attributable proportion(AP) of 0.55(95% CI 0.43, 0.59), and a synergy index(S) of 3.07(95% CI 1.94, 4.84). Furthermore, when stratifying the duration of smoking cessation, long-term quitters(≥8 years) showed a lower risk of cardiovascular events compared to current smokers, regardless of whether they had MS. The hazard ratios were 0.45(95% CI 0.26, 0.78) for individuals with MS and 0.42(95% CI 0.19, 0.95) for individuals without MS. Conclusions:There is an additive interaction between smoking and MS on the risk of cardiovascular events. The coexistence of both factors significantly increases the risk of cardiovascular events.

A case of death in children with hypereosinophilia complicated with Loffler endocarditis / 中国综合临床

Objective:To investigate the clinical features of hypereosinophilia (HE) complicated with Loffler endocarditis in children, in order to analyze the etiology, clinical stage and prognosis of HE complicated with Loffler endocarditis.Methods:A case of childhood hypereosinophilia complicated with Loffler endocarditis diagnosed and treated in the Second Hospital of Hebei Medical University was analyzed retrospectively, and its clinical characteristics, causes and clinical stages were analyzed.Results:In this study, the patient was a young male. He had diarrhea for more than 40 days due to intermittent abdominal pain, dyspnea for 10 days, and poor food intake for 3 days. The blood routine showed that he was HE. The ultrasound showed Loffler endocarditis. The child had severe heart failure and multiple organ functions were involved. After active treatment, he still had multiple organ failure, and finally died of multiple organ failure and ventricular fibrillation.Conclusion:Loffler endocarditis is a serious complication of HE, with low morbidity and rare clinical manifestations. Early intervention can reduce mortality.

Risk factors of neonates with necrotizing enterocolitis require surgical therapy / 中国新生儿科杂志

Objective:To study the risk factors of surgical therapy in neonates with necrotizing enterocolitis (NEC).Methods:From January 2016 to July 2020, neonates with a confirmed diagnosis of NEC (Bell's Stage Ⅱ and above) admitted to our hospital were retrospectively enrolled. They were assigned into surgical group and conservative group according to whether surgeries were performed. The conditions during perinatal period, clinical characteristics and laboratory examinations at the onset of NEC were compared between the two groups. Multivariate Logistic regression analysis was used to determine the risk factors of surgical therapy.Results:A total of 177 neonates with NEC were identified, including 62 cases (35.0%) in the surgical group and 115 cases (65.0%) in the conservative group. Multivariate Logistic regression analysis showed that male gender ( OR=3.178,95% CI 1.457~6.929, P=0.004), comorbidity with shock ( OR=3.434, 95% CI 1.112~10.607, P=0.032), mechanical ventilation>7 d before NEC onset ( OR=3.663, 95% CI 1.098~12.223, P=0.035) and lymphocytes <2.0×10 9/L ( OR=4.121, 95% CI 1.801~9.430, P=0.001) at the onset of NEC were independent risk factors for surgical therapy. Conclusions:Male gender, comorbidity with shock, mechanical ventilation >7 d before NEC and lymphocytopenia at the onset are independent risk factors for surgical therapy in neonates with NEC (Stage Ⅱ and above).

Correlation between dyslipidemia and rheumatoid arthritis associated interstitial lung disease / 北京大学学报(医学版)

OBJECTIVE@#To study the correlation between dyslipidemia and rheumatoid arthritis associa-ted interstitial lung disease (RA-ILD) by retrospective analysis of the clinical data.@*METHODS@#The clinical data of patients with rheumatoid arthritis (RA), who were hospitalized in the Department of Rheumatism and Immunology of Peking University Shenzhen Hospital from January 2015 to July 2020 and fulfilled the criteria of the 2010 Rheumatoid Arthritis Classification Criteria established by American College of Rheumatology/European League Against Rheumatism collaborative initiative, were collected and analyzed.@*RESULTS@#There were 737 RA patients included, of whom 282(38.26%)were with interstitial lung disease (ILD). The median time from the onset of the first RA-related clinical symptoms to the onset of ILD was 13 years (95%CI 11.33-14.67). By multivariate Logistic regression analysis, we found that low-density lipoprotein cholesterol (LDL-C) was an independent risk factor for RA-ILD (OR 1.452, 95%CI 1.099-1.918, P=0.009), whereas high-density lipoprotein cholesterol (HDL-C) was a protective factor for RA-ILD (OR 0.056, 95%CI 0.025-0.125, P < 0.001). The RA patients with high LDL-C or low HDL-C had higher incidence of ILD than that of the RA patients with normal LDL-C or HDL-C(57.45% vs. 36.96%, P < 0.001; 47.33% vs. 33.81%, P < 0.001, respectively). The median time of ILD onset in the RA patients with low HDL-C was shorter than that of the RA patients with normal HDL-C [10.0(95%CI 9.33-10.67)years vs.17.0 (95%CI 14.58-19.42) years, P < 0.001]. HDL-C level was negatively correlated with disease activity. Among the RA-ILD patients, the patients with low HDL-C had higher percentage of usual interstitial pneumonia (UIP) then that of the patients with normal HDL-C (60.00% vs. 53.29%, P=0.002). The RA-ILD patients with high LDL-C had higher incidence rate of decrease in forced vital capacity (FVC) than that of the RA-ILD patients with normal LDL-C (50.00% vs. 21.52%, P=0.015). The RA-ILD patients with low HDL-C had higher incidence rate of decrease in FVC (26.92% vs. 16.18%, P=0.003) and carbon monoxide diffusion (80.76% vs. 50.00%, P=0.010) than that of RA-ILD patients with normal HDL-C.@*CONCLUSION@#LDL-C was possibly a potential independent risk factor for RA-ILD. HDL-C was possibly a potential protective factor for RA-ILD. HDL-C level was negatively correlated with disease activity of RA. The median time of ILD onset in the RA patients with low HDL-C was significantly shorter than that of the RA patients with normal HDL-C.

Application of individualized teaching based on the good-will preposing theory in the teaching of practical nursing students in the department of oncology / 中华医学教育探索杂志

Objective:To analyze the effectiveness of individualized teaching based on the good-will preposing theory in the teaching of practical nursing students in the department of oncology.Methods:Eighty practical nursing students who were accepted by the department of oncology from January 2019 to October 2020 were selected, and they were randomly divided into routine group and research group with 40 students in each group. The routine group was taught by conventional methods and the research group was taught by individualized teaching methods based on the good-will preposing theory, respectively. The scores of theory and practice assessment and the changes of willingness and confidence of practical nurses in the department of oncology before and after the teaching, and the satisfaction with the teaching mode were compared between the two groups. SPSS 25.0 was used for t test and rank sum test. Results:The scores of theoretical and practical assessment in the two groups after teaching were higher than those before teaching ( P<0.05), and the scores of theoretical and practical assessment in the study group were higher than those in the routine group ( P<0.05). There were statistically significant differences in the grade distribution of willingness and confidence to undertake the career of oncology between the two groups of practical nursing students after teaching compared with that before teaching ( P<0.05). In the study group, the satisfaction scores of meeting learning willingness, improving learning enthusiasm, improving teaching efficiency, and strengthening the interaction between teachers and students in study group were higher than those in routine group ( P<0.05). Conclusion:Application of individualized teaching based on the good-will preposing theory among practical nursing students in the department of oncology may improve assessment performance, enhance their willingness and confidence to undertake the career of oncology, and improve their teaching satisfaction.

Effect of Asiaticoside on Expression of Th17/Treg Cells in DBA/1 Mice with Collagen-Induced Arthritis / 中国实验方剂学杂志

ObjectiveTo observe the effect of asiaticoside （AC） on the expression of T helper 17 （Th17） cells and regulatory T （Treg） cells in DBA/1 mice with collagen-induced arthritis （CIA）. MethodMale SPF DBA/1 mice were randomized into six groups according to body weight： control group， CIA group， methotrexate group （MTX group， ip， 0.5 mg·kg-1）， and AC low-， medium-， and high-dose groups （ig， 5， 15， 45 mg·kg-1， respectively）. Modeling was performed in rats other than the control group. To be specific， they were immunized with bovine type Ⅱ collagen and complete Freund's adjuvant on the first day and with bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21st day. Administration began on the day of the second immunization， once a day for 28 days. On the 49th day， related tissues were collected. Then， hematoxylin-eosin （HE） staining was performed to observe the pathological changes of the joints. Immunohistochemical method was used to detect the expression of interleukin-17 （IL-17） and forkhead box protein-3 （FoxP3）， the markers of Th17 and Treg cells， respectively， immunofluorescence double staining the expression of IL-17 and FoxP3 in CD4+T cells of mouse joint tissue， and flow cytometry the proportions of Th17 and Treg cells in mouse lymph nodes. ResultCompared with the control group， CIA group demonstrated joint disorder， damage of articular cartilage and bone， severe bone erosion （P<0.01）， increase in stained CD4 and IL-17 and the integral absorbance （IA） （P<0.01）， decrease in stained FoxP3 and the IA （P<0.01）， rise of Th17/Treg ratio （P<0.01）， elevation of Th17 expression in mouse lymph nodes （P<0.01）， and reduction in Treg expression （P<0.01）. Compared with CIA group， MTX group and three AC groups showed normal joints， alleviated bone erosion and damage， intact and smooth joint surface， and decrease in stained IL-17 and IA （P<0.05， P<0.01）， and MTX group and AC medium-dose and high-dose groups registered decrease in stained CD4 and IA （P<0.01） and reduction in Th17/Treg ratio （P<0.05， P<0.01）. Moreover， AC medium-dose and high-dose groups showed rise in stained FoxP3 and IA （P<0.05， P<0.01）. In the lymph nodes of mice， decrease in expression of Th17 cells （P<0.05， P<0.01） and the increase in expression of Treg cells （P<0.05， P<0.01） were observed in all the three AC group. ConclusionAC can regulate Th17/Treg balance by inhibiting the expression of Th17 cells and promoting the expression of Treg cells in CIA mice.

Strike Velocity Prediction of Stick Blunt Instruments Based on Backpropagation Neural Network / 法医学杂志

OBJECTIVES@#To analyze and predict the striking velocity range of stick blunt instruments in different populations, and to provide basic data for the biomechanical analysis of blunt force injuries in forensic identification.@*METHODS@#Based on the Photron FASTCAM SA3 high-speed camera, Photron FASTCAM Viewer 4.0 and SPSS 26.0 software, the tester's maximum striking velocity of stick blunt instruments and related factors were calculated and analyzed, and inputed to the backpropagation (BP) neural network for training. The trained and verified BP neural network was used as the prediction model.@*RESULTS@#A total of 180 cases were tested and 470 pieces of data were measured. The maximum striking velocity range was 11.30-35.99 m/s. Among them, there were 122 female data, the maximum striking velocity range was 11.63-29.14 m/s; there were 348 male data, the maximum striking velocity range was 20.11-35.99 m/s. The maximum striking velocity of stick blunt instruments increased with the increase of weight and height, but there was no obvious increase trend in the male group; the maximum striking velocity decreased with age, but there was no obvious downward trend in the female group. The maximum striking velocity of stick blunt instruments has no significant correlation with the material and strike posture. The root mean square error (RMSE), the mean absolute error (MAE) and the coefficient of determination (R2) of the prediction results by using BP neural network were 2.16, 1.63 and 0.92, respectively.@*CONCLUSIONS@#The prediction model of BP neural network can meet the demand of predicting the maximum striking velocity of different populations.

Reconstruction and Quantitative Evaluation of Blunt Injury Cases by Finite Element Method / 法医学杂志

OBJECTIVES@#To reconstruct the cases of acceleration craniocerebral injury caused by blunt in forensic cases by finite element method (FEM), and to study the biomechanical mechanism and quantitative evaluation method of blunt craniocerebral injury.@*METHODS@#Based on the established and validated finite element head model of Chinese people, the finite element model of common injury tool was established with reference to practical cases in the forensic identification, and the blunt craniocerebral injury cases were reconstructed by simulation software. The cases were evaluated quantitatively by analyzing the biomechanical parameters such as intracranial pressure, von Mises stress and the maximum principal strain of brain tissue.@*RESULTS@#In case 1, when the left temporal parietal was hit with a round wooden stick for the first time, the maximum intracranial pressure was 359 kPa; the maximum von Mises stress of brain tissue was 3.03 kPa at the left temporal parietal; the maximum principal strain of brain tissue was 0.016 at the left temporal parietal. When the right temporal was hit with a square wooden stick for the second time, the maximum intracranial pressure was 890 kPa; the maximum von Mises stress of brain tissue was 14.79 kPa at the bottom of right temporal lobe; the maximum principal strain of brain tissue was 0.103 at the bottom of the right temporal lobe. The linear fractures occurred at the right temporal parietal skull and the right middle cranial fossa. In case 2, when the forehead and left temporal parietal were hit with a round wooden stick, the maximum intracranial pressure was 370 kPa and 1 241 kPa respectively, the maximum von Mises stress of brain tissue was 3.66 kPa and 26.73 kPa respectively at the frontal lobe and left temporal parietal lobe, and the maximum principal strain of brain tissue was 0.021 and 0.116 respectively at the frontal lobe and left temporal parietal lobe. The linear fracture occurred at the left posterior skull of the coronary suture. The damage evaluation indicators of the simulation results of the two cases exceeded their damage threshold, and the predicted craniocerebral injury sites and fractures were basically consistent with the results of the autopsy.@*CONCLUSIONS@#The FEM can quantitatively evaluate the degree of blunt craniocerebral injury. The FEM combined with traditional method will become a powerful tool in forensic craniocerebral injury identification and will also become an effective means to realize the visualization of forensic evidence in court.

Study of protective effect and mechanism of vitamin C in lipopolysaccharide-induced septic renal injury / 中华危重病急救医学

Objective:To explore the protective effect and its mechanism of vitamin C on septic renal injury induced by lipopolysaccharide (LPS).Methods:Renal tubular epithelial cells HK-2 were induced with 10 mg/L LPS for 8 hours and 12 hours, respectively, and then 0.5 mmol/L and 1 mmol/L vitamin C were added, respectively. Cell viability was measured using cell proliferation and toxicity assay cell counting kit-8 (CCK-8) to determine suitable condition for subsequent experiments. HK-2 cells were divided into control group, LPS group and LPS+vitamin C group (LPS+VC group). The contents of necrosis factors phosphorylated mixed lineage kinase domain-like protein (p-MLKL) and phosphorylated receptor-interacting protein kinase 3 (p-RIPK3) were measured by Western blotting. The contents of inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA) in each group. Differences among the groups were compared.Results:CCK-8 showed that 1 mmol/L vitamin C improved the survival rate of HK-2 cells to 86% after 12 hours of LPS induction, so this condition was selected for subsequent experiments. After 12 hours LPS induction in HK-2 cells, the expressions of p-MLKL and p-RIPK3 were significantly higher than those of the control group, and the levels of IL-1β and TNF-α were also significantly higher than those of the control group [IL-1β (ng/L): 23.2±1.4 vs. 12.8±3.9, TNF-α (ng/L): 36.4±3.9 vs. 11.6±1.8, both P < 0.05], indicating the co-existence of cell necrosis and inflammation. Compared with LPS group, 1 mmol/L vitamin C significantly decreased the protein expression of p-MLKL and p-RIPK3, and also significantly decreased the levels of IL-1β and TNF-α [IL-1β (ng/L): 19.8±0.7 vs. 23.2±1.4, TNF-α (ng/L): 17.4±5.8 vs. 36.4±3.9, both P < 0.05]. Conclusion:Vitamin C can alleviate LPS-induced HK-2 cell damage, and reduce the expressions of necrotic factors and inflammatory factors.

Meta-analysis of Risk Factors for Rheumatoid Arthritis associated Interstitial Lung Disease / 中华风湿病学杂志

Objective:To evaluate the risk factors of rheumatoid arthritis associated interstitial lung disease (RA-ILD).Methods:Databases including PubMed, Sinomed, Embase, Wiley Online library were searched to collect studies on risk factors of RA-ILD. The deadline of the search was January 1 2021. Newcastle-Ottawa Scale (NOS) was used to assess the literature quality, data was extracted and analyzed by Statistical software in eligible studies.Results:This meta-analysis included 36 studies involving 3 280 patients with RA-ILD and 25 510 RA controls patients. The Incidence of RA-ILD was 6.25%. The risk of RA-ILD was 2.51 times greater in men than in women [ OR(95% CI)=2.51(2.25, 2.80)]. The mean onset age of patients with RA-ILD was 7.47 years [56.50 vs 49.04, 95% CI(6.56, 8.38)] older than those of patients with RA-nILD. The mean duration of patients with RA-ILD was 1.11 years longer than that of patients with RA-nILD [7.73 vs 6.62, 95% CI(0.68, 1.55)]. The risk of RA-ILD was two times greater in smoker than in non-smoker [ OR(95% CI)=2.25(2.01, 2.52]). Moderate evidence indicated that higher erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), disease activity score in 28 joints (DAS28)-ESR were risk factors for RA-ILD[Stan-dard Mean Difference ( SMD)(95% CI)=0.25(0.18, 0.31); SMD(95% CI)=0.25(0.18, 0.32); SMD(95% CI)=0.36(0.27, 0.45), respectively). The pooled [ OR(95% CI)=1.71(1.45, 2.01)] in rheumatoid factor (RF) positive and [ OR(95% CI)=2.41(1.80, 3.23)] anti-CCP antibody positive for the risk of RA-ILD. Conclusion:Male, smoking, older age of disease onset, long disease duration, elevated erythrocyte sedimentation rate, high C-reactive protein level, high DAS28-ESR, positive RF and anti-cyclic peptide containing citrulline antibody were risk factors for RA-ILD.

Effects of dexmedetomidine on nuclear factor-KB inhibitor protein kinase/ nuclear factor-KB inhibitor protein a/nuclear factor-KB pathway and cognitive dysfunction in rats with post-traumatic stress disorder / 解剖学报

Objective To investigate the effects of dexmedetomidine (DEX) on the nuclear factor-KB inhibitor protein kinase (IKK)/nuclear factor-KB inhibitor protein a (IKB(X)/nuclear factor-KB (N F - K B) pathway and cognitive dysfunction in rats with post-traumatic stress disorder (PTSD) . Methods Rats were randomly divided into control group, model group, positive group and DEX group. Except for the control group, the PTSD model was constructed by single prolonged stress method (SPS), and the corresponding drugs were given after the completion the model. Open field test and Morris water maze method were used to detect the autonomous activity, learning and memory ability of rats; HE staining was used to observe the morphological characteristics of cerebral cortex and hippocampus; ELISA and Western blotting were used to detect the contents of interleukin (IL)-1(3, IL-6, tumor necrosis factor a (TNF-a) and the expression levels of IKK, IKB(X, purinergic ligand-gated ion channel 7 receptor (P2X7R), leucine-rich repeat domain protein 3(NALP3) in hippocampus; the NF-KB activity was assessed by electrophoretic mobility shift assay (EMSA). Results Compared with the control group, the cerebral cortex and hippocampal CA1 region of model group were in structural disorders, nuclear pyysis and other pathological changes happend, learning and memory ability of rats decreased (P < 0. 05), contents of IL-lp, IL-6 and TNF-a, expression levels of IKK, IKB(X, P2X7R and NALP3, NF-KB activity in hippocampus increased (P<0. 05); Compared with the model group, the pathological phenomena in cerebral cortex and hippocampal CA1 area of rats in positive group and DEX group were in alleviated, and the changes of the above indexes were opposite to those of model group (P<0. 05) . Conclusion DEX can significantly improve the autonomous activity ability and learning and memory ability in PTSD rats, reduce inflammatory reaction in hippocampus and improve cognitive dysfunction, which may be related to the down-regulation of IKK/TKBQ!/NF-KB pathway.

Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids / 生理学报

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.

Exploring the mechanism of Buxue Yimu Pill on hemorrhagic anemia through molecular docking, network pharmacology and experimental validation / 中国天然药物

Buxue Yimu Pill (BYP) is a classic gynecological medicine in China, which is composed of Angelica sinensis (Oliv.) Diels, Leonurus japonicus Houtt, Astragalus membranaceus (Fisch.) Bunge, Colla corii asini and Citrus reticulata Blanco. It has been widely used in clinical therapy with the function of enriching Blood, nourishing Qi, and removing blood stasis. The current study was designed to determine the bioactive molecules and therapeutic mechanism of BYP against hemorrhagic anemia. Herein, GC-MS and UPLC/Q-TOF-MS/MS were employed to identify the chemical compounds from BYP. The genecards database (https: //www.genecards.org/) was used to obtain the potential target proteins related to hemorrhagic anemia. Autodock/Vina was adopted to evaluate the binding ability of protein receptors and chemical ligands. Gene ontology and KEGG pathway enrichment analysis were conducted using the ClusterProfiler. As a result, a total of 62 candidate molecules were identified and 152 targets related to hemorrhagic anemia were obtained. Furthermore, 34 active molecules and 140 targets were obtained through the virtual screening experiment. The data of molecular-target (M-T), target-pathway (T-P), and molecular-target-pathway (M-T-P) network suggested that 32 active molecules enhanced hematopoiesis and activated the immune system by regulating 57 important targets. Pharmacological experiments showed that BYP significantly increased the counts of RBC, HGB, and HCT, and significantly down-regulated the expression of EPO, IL-6, CSF3, NOS2, VEGFA, PDGFRB, and TGFB1. The results also showed that leonurine, leonuriside B, leosibiricin, ononin, rutin, astragaloside I, riligustilide and levistolide A, were the active molecules closely related to enriching Blood. In conclusion, based on molecular docking, network pharmacology and validation experiment results, the enriching blood effect of BYP on hemorrhagic anemia may be associated with hematopoiesis, anti-inflammation, and immunity enhancement.

Differentially expressed microRNAs in the testis of male rats exposed to cigarette smoke: Screening and function verification / 中华男科学杂志

Objective@#To screen differentially expressed miRNAs in the testis of male rats exposed to cigarette smoke (CS) and identify the early molecular markers of CS-induced apoptosis of testicular cells.@*METHODS@#We randomly divided 200 SPF male SD rats into blank control and low-dose (10 non-filter cigarettes/d), medium-dose (20 non-filter cigarettes/d) and high-dose (30 non-filter cigarettes/d) CS exposure groups. After 2, 4, 6, 8 and 12 weeks of CS exposure, we observed the histopathological changes of the testis by HE staining, detected the apoptosis of the testicular cells by TUNEL, and determined the expressions of caspase-3 and caspase-9 in the testis tissue by immunohistochemistry, RT-PCR and Western blot. Based on the laboratory results, we selected 4 testicular samples from the 12-week high-dose group and another 4 from the control for miRNA microarray-based screening, bioinformatics analysis, and verification of differentially expressed miRNAs in all the animals by RT-PCR.@*RESULTS@#Compared with the controls, the CS-exposed rats showed dose- and time-dependent increase in the atrophy of the testis and significantly increased number of apoptotic testis cells from the 6th week of exposure (P < 0.05), with dramatically up-regulated expressions of caspase-3 (P < 0.01) and caspase-9 protein and mRNA (P < 0.05) in the testis tissue. Microarray-based screening and RT-PCR revealed 5 differentially expressed miRNAs in the testis of the CS-exposed rats, of which miR-138-5p, miR-181d-5p, miR-19a-3p and miR-3588 were down-regulated, and miR-155-5p up-regulated, and the target genes of the differentially expressed miRNAs positively regulated the apoptosis of the testicular cells.@*CONCLUSIONS@#The differentially expressed miRNAs miR-155-5p, miR-138-5p, miR-181d-5p, miR-19a-3p and miR-3588 regulate CS-induced apoptosis of testicular cells, and may become biomarkers for early diagnosis and prognosis of CS-induced spermatogenesis obstruction.《.

Anticoagulant therapy in elderly patients with nephrotic syndrome / 中华老年医学杂志

There is a high incidence of thromboembolic events in patients with nephrotic syndrome(NS), and the risk of thrombosis and bleeding increases in the elderly.On the basis of the guidelines of Kidney Disease: Improving Global Outcomes(KDIGO)glomerulonephritis 2020, the risk assessment of thromboembolism and bleeding, the timing of anticoagulant therapy and prevention and the selection of drugs for elderly NS individuals are discussed in this review.

Effect of Fangji Huangqitang on Function of Human Umbilical Vein Endothelial Cells / 中国实验方剂学杂志

Objective:To study the effects of Fangji Huangqitang（FJHQT） on migration， adhesion，invasion and tube formation of human umbilical vein endothelial cells （HUVECs） induced by vascular endothelial growth factor （VEGF）. Method:HUVECs were induced by VEGF （20 μg·L^-1） <italic>in vitro</italic>. The effects of FJHQT （0.25，0.5，1 g·L^-1） on HUVECs were detected by methyl thiazolyl tetrazolium（MTT）， scratch repair， transwell migration， adhesion， invasion and tube formation. Protein in HUVECs was extracted and protein expression levels of phosphorylated Janus kinase 1 （p-JAK1） were detected by Western blot. Result:Compared with control group， VEGF （20 μg·L^-1） can increase the proliferation， scratch repair， transwell migration， adhesion， invasion and tube formation of HUVECs cells （<italic>P</italic><0.01）， compared with VEGF group， FJHQT （0.25，0.5，1 g·L^-1） ，there is no significant effect on the proliferation of HUVECs induced by VEGF for 24 hours， but it can significantly reduce the scratch repair， migration， adhesion， invasion and tube formation of HUVECs induced by VEGF within 24 hours （<italic>P</italic><0.05）. Compared with blank group， VEGF could induce abnormal elevation of p-JAK1 in HUVECs （<italic>P</italic><0.01）， while FJHQT （0.25，0.5，1 g·L^-1） could significantly reduce the expression levels of p-JAK1 （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:FJHQT can inhibit the migration， adhesion and invasion of HUVECs， the mechanism may be related to JAK1.