Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Laparoscopic radical anterograde modular pancreatosplenectomy for pancreatic tail cancer / 中华普通外科杂志

Objective:To evaluate the safety and feasibility of laparoscopic radical anterograde modular pancreatosplenectomy (Lap-RAMPS).Methods:From Jan 2014 to Dec 2020, the clinical data of 83 patients who underwent laparoscopic radical resection for pancreatic tail cancer in LiHuili Hospital of Ningbo Medical Center were retrospectively analyzed.Results:Eighty-three cases were divided into Lap-RAMPS group (44 cases) and laparoscopic conventional distal pancreatectomy and splenectomy(Lap-CDP) group (39 cases). There were no significant differences in the duration of surgery [(245.34±70.30) min vs. (239.87±68.10) min], intraoperative blood lose [(159.32±115.60) ml vs. (208.97±161.70) ml] and intraoperative transfusions (2 cases vs. 3 cases) between the two groups ( P>0.05). There were no statistical significance in both groups in postoperative pancreatic fistula, postoperative bleeding grade, postoperative gastric emptying delay, Clavien-Dindo complication and postoperative hospital stay ( P>0.05). There were statistically significant differences in the negative margin rate (93.2% vs. 76.9%),lymph node harvest(12.91±8.24 vs. 8.49±6.85) and median survival time (25.0 months vs. 15.0 months) between the two groups ( P<0.05). Conclusion:Lap-RAMPS for pancreatic tail cancer is safe and feasible, increasing the negative rate of pancreatic margins, improving the lymph node harvest, and prolonging patients' survival time.

A pilot study of late-onset neuromyelitis optica spectrum disorder disease based on brain three-dimensional structural MRI / 中华放射学杂志

Objective:To explore the different patterns of brain structural abnormalities in patients with delayed neuromyelitis optica pedigree disease (LO-NMOSD) and its relationship with clinical neuropsychological scale score based on the quantitative analysis of three-dimensional (3D) brain structure MRI.Methods:Patients with neuromyelitis optica pedigree disease in remission (NMOSD group) who received treatment at Jilin University First Hospital from January 2016 to December 2018 were prospectively included and divided into LO-NMOSD subgroup and early-onset NMOSD (EO-NMOSD) subgroup according to whether the age of first onset was>50 years. Another age-and sex-matched healthy volunteers with NMOSD patients were recruited as the control group. 3D brain T 1WI and T 2 fluid-attenuated inversion recovery sequence imaging were acquired, and clinical data, neuropsychological scores of all subjects were analyzed. Total gray matter volume (GMV), cerebral gray matter fraction (GMF), cerebral white matter fraction (WMF), and cerebral white matter high signal fraction (WMHF) were obtained by quantitative analysis of MRI data using voxel-based morphology and lesion segmentation tool techniques. Analysis of covariance was used to compare the differences in brain structure between LO-NMOSD subgroup and EO-NMOSD subgroup, NMOSD group and control group. Partial correlation analysis was used to analyze the correlation between GMF, WMHF and patient clinical data, neuropsychological scale scores, and the correlation between WMHF and GMF, WMF. Results:There were 47 cases in the NMOSD group, including 7 males and 40 females aged 18-66 years. Among them, there were 20 cases in the LO-NMOSD subgroup and 27 cases in the EO-NMODS subgroup. The control group consisted of 50 individuals (13 males and 37 females, aged 18 to 77 years). Compared with the control group, the GMV of the right caudate nucleus in the LO-NMOSD group was reduced ( t=3.33, P<0.05), and the GMV of multiple brain regions in the bilateral frontal and temporal lobes in the EO-NMOSD group was reduced considerably (FDR corrected, P<0.05), which was consistent with the NMOSD group. After adjusting for age, there was no statistically significant difference in WMHF between the LO-NMOSD and EO-NMOSD groups ( F=0.22, P=0.644). The LO-NMOSD subgroup showed a negative correlation between global GMF and the extended disability status scale (EDSS) score ( r=-0.53, P=0.025). WMHF in the NMOSD group was positively correlated with annual recurrence rate and EDSS ( r=0.35 and 0.35, respectively, and P=0.017 and 0.018, respectively), while other indicators were not correlated ( P>0.05). The EO-NMOSD subgroup WMHF showed a negative correlation with GMF and WMF ( r=-0.76, -0.70, respectively, P<0.001). The NMOSD group showed a negative correlation between WMHF and GMF, WMF ( r=-0.38, -0.55, respectively, P<0.05). There was no correlation between WMHF and GMF, WMF in the LO-NMOSD subgroup ( P>0.05). Conclusions:The extent and location of gray matter atrophy in patients with LO-NMOSD are different from those of EO-NMOSD. The correlation between WMHF and brain structural changes and clinical data is different between the two groups of patients. These suggest that LO-NMOSD patients may have different patterns of brain structural damage.

Effects of Hcy and lncRNA ANRIL on atherosclerotic inflammatory response / 中国医师杂志

Objective:To study the relationship between the level of serum homocysteine (Hcy) and the antisense non coding gene (ANRIL) of long chain non coding RNA (lncRNA) cell cycle dependent kinase inhibitor 2B gene, and the effect on Atherosclerosis inflammation, that is, the expression of interleukin-10 (IL-10) and Monocyte chemoattractant protein-1 (MCP-1) in Human umbilical vein endothelial cell (HUVEC).Methods:HUVEC was cultured in vitro and cells were treated with different concentration gradients (blank control group, 0.5, 1.0, 2.0, 5.0 mmol/L) of Hcy. The expression level of lncRNA ANRIL was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of MCP-1 and IL-10. LipoFilter transfection reagents were used to transfect shANRIL and shNC into different cells, respectively. In the above experiment, the optimal Hcy concentration (5.0 mmol/L) was selected for intervention for 24 hours. Western blot was used to detect the protein expression levels of MCP-1 and IL-10.Results:After 24 hours of intervention with different concentrations of Hcy in HUVEC, Hcy significantly damaged endothelial cells, and the higher the Hcy concentration, the more severe the cell damage. Compared with the blank control group, the Hcy intervention group showed an increase in lncRNA ANRIL and MCP-1, while IL-10 decreased (all P<0.05); As the concentration of Hcy intervention increases, IL-10 decreases, while lncRNA ANRIL and MCP-1 increased (all P<0.05). Compared with the blank control group, the Hcy group, the shNC+ Hcy group, and the shANRIL+ Hcy group had lower levels of IL-10 protein expression and higher levels of MCP-1 protein expression (all P<0.05). Compared with the shANRIL+ Hcy group, the Hcy group and the shNC+ Hcy group had lower levels of IL-10 protein expression and higher levels of MCP-1 protein expression (all P<0.05). There was no statistically significant difference in the expression levels of IL-10 protein and MCP-1 protein between the shNC+ Hcy group and the Hcy group (all P>0.05). Conclusions:Hcy upregulates MCP-1 expression and downregulates IL-10 expression by promoting lncRNA ANRIL expression. Thus, it can promote cellular inflammatory reaction and participate in Atherosclerosis.

Mediating role of family function between coping strategies and emotional behavior in children with chronic superficial gastritis / 四川精神卫生

BackgroundChronic superficial gastritis （CSG） is a common clinical disease in children. The emotional behavior of CSG children is susceptible due to them suffering from such disease at young age. ObjectiveTo explore the impact of coping strategies on emotional behavior and the effect of family function in children with CSG， and to provide references for clinical intervention in CSG children with emotional behavior problems. MethodsA total of 177 children with CSG admitted to Anhui Children's Hospital from June 2019 to January 2023 were selected as the research subjects. Investigation on family function， emotional and behavioral problems and coping strategies of children was conducted by employing the Family APGAR index （APGAR）， the Strengths and Difficulties Questionnaire （SDQ） and Coping Strategies Questionnaire （CSQ）. The structural equation model was used to test the mediating effect of family function between coping strategies and emotional behaviors. ResultsThe APGAR score was negatively correlated with both SDQ score and negative coping strategies score （r=-0.507， -0.551， P<0.01）， but was positively correlated with positive coping strategy score （r=0.579， P<0.01）. The positive coping strategy score was negatively correlated with SDQ score （r=-0.539， P<0.01）， while the negative coping strategy score was positively correlated with SDQ score （r=0.543， P<0.01）. The result showed that family function played a partial mediating role between positive coping strategies and emotional behavior ［indirect effect was -0.133 （95% CI： -0.256~-0.079， P<0.01）， accounting for 29.40% of the total effect］. The same mediating effect happened between negative coping strategies and emotional behavior ［indirect effect was 0.093 （95% CI： 0.198~0.045， P<0.01）， accounting for 28.50% of the total effect］. ConclusionCoping strategies of CSG children can affect emotional behavior directly and indirectly with family function playing a partial intermediary effect.

Pricking and cupping at Jianbo area combined with conventional acupuncture for scapulohumeral periarthritis of frozen stage: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of conventional acupuncture combined with pricking and cupping at Jianbo area and conventional acupuncture in the treatment of scapulohumeral periarthritis of frozen stage.@*METHODS@#A total of 66 patients with scapulohumeral periarthritis of frozen stage were randomly divided into a combination group (31 cases) and an acupuncture group (35 cases, 1 case dropped off). Both groups were given functional exercise. Patients in the acupuncture group were treated with acupuncture at Jianyu (LI 15), Jianliao (TE 14), Binao (LI 14) and ashi point on the affected side, once every other day, three times a week, for a total of 4 weeks. On the basis of treatment in the acupuncture group, the patients in the combination group were treated with pricking and cupping at Jianbo area (the area surrounded by the 3 acupoints of Tianzong [SI 11], Naoshu [SI 10] and Jianzhen [SI 9]), once a week for 4 weeks. The University of California-Los Angeles (UCLA) shoulder joint score, visual analogue scale (VAS) score before treatment, after treatment and after 6 months of treatment completion (follow-up) and tenderness threshold before and after treatment, and the clinical effects of the two groups after treatment and in follow-up were evaluated.@*RESULTS@#In the two groups, after treatment and in follow-up, the UCLA shoulder joint scores were higher than those before treatment (P<0.05), and the VAS scores were lower than those before treatment (P<0.05). In the combination group, after treatment and in follow-up, the UCLA shoulder joint score was higher than that of the acupuncture group (P<0.05), and the VAS score was lower than that of the acupuncture group (P<0.05). After treatment, the tenderness thresholds of the two groups were higher than those before treatment (P<0.05), and the tenderness threshold in the combination group was higher than that in the acupuncture group (P<0.05). After treatment and in follow-up, the cured and markedly effective rate of the combination group was 48.4% (15/31) and 51.6% (16/31) respectively, which was higher than 23.5% (8/34) and 23.5% (8/34) of the acupuncture group (P<0.05).@*CONCLUSION@#Pricking and cupping in Jianbo area combined with conventional acupuncture can improve shoulder joint function and relieve shoulder joint pain in patients with scapulohumeral periarthritis of frozen stage, and the curative effect is better than that of single conventional acupuncture.

Erythrocyte membrane-associated protein inhibiting Th17 cell differentiation via IL-6 / STAT3 / ROR-γt signaling pathway in experimental autoimmune encephalomyelitis mice / 解剖学报

Objective To explore the effect of exogenous and endogenous erythrocyte membrane-associated protein (ERMAP) on helper T cell 17 (Th17) cell differentiation through interleukin 6 / signal transducers and activators of transcription 3 / retionoid-related orphan nuclear receptor-γt(IL-6 / STAT3 / ROR-γt) signal pathway in the mouse model of experimental autoimmune encephalomyelitis (EAE) . Methods Using flow cytometry to verify the function of ERMAP-Ig fusion protein at different concentrations; Agarose gel electrophoresis was performed to identify ERMAP knockout mice. Flow cytometry was performed to detect the effect of ERMAP-Ig fusion protein on Th17 cell differentiation in vitro. Forty 6-week-old normal C57BL / 6 mice were randomly divided into 2 groups to establish EAE models, control-Ig and ERMAP-Ig groups, with 20 mice in each group; Clinical scores were recorded; Flow cytometry was performed to detect Th17 cell differentiation in EAE mice in vivo. Forty 6-week-old identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models. Identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models, ERMAP

Mechanism of electroacupuncture regulating the ligand pathway of tyrosine kinase receptor in improving vascular dementia / 解剖学报

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.

Effect of baicalin modulation of TLR4/MAPK/NF-ΚB signaling pathway on renal fibrosis in rats with diabetic nephropathy / 中国药理学通报

Aim To investigate the protective effect of baicalin on renal fibrosis in rats with diabetic nephrop- III (Col- III) athy (DN) and to investigate its mechanism of action. Methods A rat model of diabetic nephropathy was constructed. The rats were randomly divided into control group, model group, baicalin low dose group, baicalin medium dose group, baicalin high dose group and metformin group, with 10 rats in each group. Except for the control group, all rats in each group were fed with streptozotocin 65 mg • kg -

Mechanism of tryptanthrin in treatment of ulcerative colitis in mice based on serum metabolomics / 中国中药杂志

This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.

Synthesis and anti-HCC activity of full 2ʹ-F/OMe-siRNA encapsulated with neutral cytidinyl/cationic lipid / 药学学报

A variety of full 2ʹ-F/OMe-modified siRNAs were designed and synthesized, and the activity against hepatocellular carcinoma Huh-7 and HepG2 cells was evaluated. K&A DNA/RNA H-8 synthesizer was used to synthesize siRNAs, and neutral cytidinyl lipid DNCA mixed with cationic lipid CLD were used to transfect siRNA. By RT-qPCR and CCK-8 assay, the target gene silence and the proliferation of Huh-7 and HepG2 cells were detected. The siRNAs loading into Ago2 protein was detected by RNA-binding protein immunoprecipitation. Drug uptake and cell apoptosis were detected by flow cytometry, and the expression of PLK1 protein was detected by Western blot. Partial full 2ʹ-F/OMe modified siRNAs, especial siPLK1A3, increased the uptake of Huh-7 cells, enhanced their binding to Ago2 and gene silencing activity, down-regulated PLK1 protein, as well as induced more Huh-7 cell apoptosis and proliferation inhibition activity. It provides important data for the development of novel siRNA modification patterns and anti-HCC formulations.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study / 亚洲男科学杂志(英文版)

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

Establishment and Evaluation of Rat Model for Chronic Obstructive Pulmonary Disease with Lung-spleen Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo establish and evaluate a chronic obstructive pulmonary disease （COPD） model with lung-spleen qi deficiency. MethodA rat model mimicking COPD with lung-spleen qi deficiency was established by the combination of cigarette smoking and intratracheal instillation of lipopolysaccharide （LPS） along with gavage of Sennae Folium infusion. Forty male SPF-grade SD rats were randomly assigned to blank， model， and low- （L-FXY）， medium- （M-FXY）， and high-dose （H-FXY） Sennae Folium infusion groups. Other groups except the blank group were exposed to daily cigarette smoke， with LPS administrated via intratracheal instillation on the 1st and 14th days. On the 28th day of modeling， the L-FXY， M-FXY， and H-FXY groups were administrated with Sennae Folium infusion at 5， 10， and 20 g·kg-1， respectively， and at 4 ℃ for three weeks. The modeling lasted for 49 days. The general conditions （body mass， food intake， fecal water content， and anal temperature） and behaviors （grip strength test and tail suspension test） of rats in different groups were examined. The lung function， lung histopathology， D-xylose， amylase， and gastrin levels in the serum， interleukin（IL）-1β and IL-6 levels in the alveolar lavage fluid， levels of T-lymphocyte subsets （CD4+， CD8+， and CD4+/CD8+） in the peripheral blood， and thymus and spleen indices were measured. ResultTwo rats died in the H-FXY group. Compared with the blank group， both the M-FXY and H-FXY groups exhibited reduced body mass and food intake （P<0.01） and increased fecal water content （P<0.01）. The anal temperature in the H-FXY group was lower than that in the blank group （P<0.01）. The grip strength decreased in the modeling groups compared with the blank group （P<0.01）， and the duration of immobility in the tail suspension test increased in the M-FXY and H-FXY groups （P<0.05， P<0.01）. Compared with the blank group， the modeling groups showed reduced 0.3 second forced expiratory volume （FEV0.3）， FEV0.3/forced vital capacity （FVC）（P<0.01）， thickening of bronchial walls， proliferation of goblet cells， and the presence of emphysematous changes. In terms of gastrointestinal function， the M-FXY and H-FXY groups had lower levels of D-xylose， gastrin， and α-amylase than the blank group （P<0.01）. Regarding the immune and inflammatory indices， the M-FXY and H-FXY groups showed lower thymus and spleen indices than the blank group （P<0.01）. Compared with the blank group， the modeling groups presented lowered CD4+ level （P<0.01） and CD4+/CD8+ ratio （P<0.05， P<0.01） in the peripheral blood and elevated levels of IL-1β and IL-6 in the alveolar lavage fluid （P<0.01） than the blank group. ConclusionA model of COPD with lung-spleen Qi deficiency was established through the combination of daily cigarette smoke， intratracheal instillation with LPS， and gavage of Sennae Folium infusion. The comprehensive evaluation results suggested medium-dose （10 g·kg-1） Sennae Folium infusion for gavage during the modeling of COPD with lung-spleen Qi deficiency.

Research progress on the application of deep learning in choroidal segmentation / 国际眼科杂志(Guoji Yanke Zazhi)

In recent years, ophthalmology, as one of the medical fields highly dependent on auxiliary imaging, has been at the forefront of the application of deep learning algorithm. The morphological changes of the choroid are closely related to the occurrence, development, treatment and prognosis of fundus diseases. The rapid development of optical coherence tomography has greatly promoted the accurate analysis of choroidal morphology and structure. Choroidal segmentation and related analysis are crucial for determining the pathogenesis and treatment strategies of eye diseases. However, currently, choroidal mainly relies on tedious, time-consuming, and low-reproducibility manual segmentation. To overcome these difficulties, deep learning methods for choroidal segmentation have been developed in recent years, greatly improving the accuracy and efficiency of choroidal segmentation. The purpose of this paper is to review the features of choroidal thickness in different eye diseases, explore the latest applications and advantages of deep learning models in measuring choroidal thickness, and focus on the challenges faced by deep learning models.

Tongxie Yaofang Regulates T Lymphocyte Subsets to Improve Immune Microenvironment of Colorectal Cancer Under Chronic Stress / 中国实验方剂学杂志

ObjectiveTo explore the effect of Tongxie Yaofang on the immune microenvironment of colorectal cancer in mice under chronic stress and the underlying mechanism. MethodA total of 40 male SPF BABL/C mice were randomized into normal group， stress group， Tongxie Yaofang group （13.65 g·kg-1）， and Tongxie Yaofang-stress group （13.65 g·kg-1）， with 10 in each group. Chronic restraint stress was induced in mice and administration （ig） of Tongxie Yaofang began after 7 days of stress. On the 14th day， forced swim and tail suspension tests were used to examine the behavioral changes of mice after stress and the subcutaneous colorectal tumor was implanted in each group of mice. The effect of this prescription on the body mass and tumor volume of mice was observed. After the last administration， mouse serum and tumor samples were collected. The content of T lymphocytes （CD3+， CD4+， CD8+， and CD4+/CD8+） in tumor was detected by immunohistochemistry and flow cytometry and levels of corticosterone （CORT） in peripheral blood， and interleukin （IL）-2， interferon-γ （IFN-γ）， IL-6， and IL-10 in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of inhibitor of nuclear factor-κB（IκB） kinase α/β （IKKα/β）， nuclear factor-κB （NF-κB）α （IκBα）， NF-κB p65， and phosphorylated （p）-NF-κB p65 was measured by Western blot. ResultCompared with the normal group， the stress group had large tumor volume （P<0.05）， low content of CD3+， CD4+， and CD4+/CD8+ （P<0.05， P<0.01）， high content of CD8+， low content of T helper 1 （Th1）-secreted IFN-γ （P<0.05）， high content of T helper 2 （Th2）-secreted IL-10 （P<0.05） and CORT （P<0.05）， high protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05）， and low protein expression of IκBα （P<0.05）. Compared with the normal group， the Tongxie Yaofang group showed slow tumor growth， high content of CD3+， CD4+， and CD4+/CD8+ （P<0.01）， low content of CD8+ （P<0.05）， high content of Th1-secreted IL-2 and IFN-γ （P<0.05）， low content of Th2-secreted IL-6 and IL-10 （P<0.05）， low content of CORT， low protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05）， and high protein expression of IκBα （P<0.01）. Tongxie Yaofang-stress group demonstrated slower tumor growth， higher content of CD3+， CD4+， and CD4+/CD8+ （P<0.01）， smaller content of CD8+ （P<0.05）， higher content of IL-2 and IFN-γ （P<0.05）， lower content of IL-6， IL-10 （P<0.05）， and CORT （P<0.05）， lower protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05，P<0.01）， and higher protein expression of IκBα （P<0.01） than the stress group. ConclusionTongxie Yaofang can delay the growth of colorectal cancer under chronic stress and alleviate the deterioration of the immune microenvironment， possibly by inhibiting NF-κB signaling pathway， regulating the function of T lymphocyte subsets， and thus suppressing the secretion of pro-inflammatory factors.

Research progress on the role of type II innate lymphoid cells in liver diseases / 中华肝脏病杂志

Type II innate lymphoid cell (ILC2) is a newly identified innate immunological cell that belongs to the lymphocyte lineage in cell morphology, resides in the body's mucosal tissues, and has the dual functions of innate and adaptive immunity to promote tissue remodeling and repair after injury. Additionally, it is involved in the occurrence and development of a variety of liver diseases and plays an important role in maintaining the immunological homeostasis of the liver region. This article reviews the differentiation, development, and biological functions of ILC2, with particular attention to the research progress in liver diseases.

Research progression on safety verification of diving decompression procedures / 中国职业医学

@#A diving decompression procedure is a specific rule that divers should follow when they ascend and get out of water. It comes from the decompression theory and algorithm and is designed for the prevention of decompression sickness. With the ， ， development of diving technology and diving medicine the decompression procedures are constantly innovated and the new ， decompression procedure can be used in diving practice after safety verification. In principle the safety verification of ， decompression procedures should be conducted on animal experiments before human experiments and the risks of ， decompression sickness and oxygen toxicity should be systematically assessed. However the assessment methods used in ， ， ， different studies differ greatly thus it is urgent to establish a standard and universal verification system. Traditionally the risk ， ， assessment of decompression sickness and oxygen toxicity is mainly carried out by observing the incidence detecting bubbles ， theoretical calculation and lung functional test. Furthermore biochemical indicators are increasingly becoming important ， ， supplements. Due to the special underwater environment the diving operation is prone to accidents. Therefore in addition to ， verifying the safety of the new decompression procedure exploring its safety decompression limit is of great significance for the formulation of emergency decompression procedures in emergency situations. The specific approach is to shorten the decompression time and assess the safety until the critical time for detecting bubbles without the occurrence of decompression ， ， sickness is found. Future studies should continue to optimize safety assessment methods explore sensitive biochemical markers ， clarify species associations and improve verification efficiency and reliability of results.

Pathogenic detection and molecular tracing of a bacillary dysentery outbreak by Shigella sonnei in Huainan city / 中华预防医学杂志

Objective: To understand the virulence gene and drug resistance profile of Shigella sonnei outbreak in Huainan city, and conduct pathogenic traceability analysis. Methods: Water samples and feces related to an infectious diarrhea outbreak in Huainan city in August 2020 were collected for multiple pathogen detection. Virulence gene, drug sensitivity, pulse-field gel electrophoresis and whole genome sequencing of Shigella isolates were analyzed respectively. Results: 38 strains of Shigella sonnei were detected in 56 samples of mucilage feces with a positive rate 67.86%, and all serotypes were Shigella sonnei Phase I. Three strains of Shigella sonnei were detected by fluorescence PCR in the Gram-negative (GN) bacterial enrichment solution of terminal water and well water. Virulence genes were ipaH positive (38), ipaH/ial (31) and ipaH/ial/sen positive (1), respectively. The drug resistance spectrum showed that 9 of 14 antibiotics were 100% resistant, and only imipenem, chloramphenicol, ceftazidime and ciprofloxacin were effective drugs. XbaⅠ restriction enzyme map type of 36 isolates was completely consistent, and the ST type analysis of 3 strains was ST152. Whole genome sequencing and analysis verified that the outbreak was caused by a single clonal group of strains, and revealed that the isolates of the outbreak were clustered into a large cluster with 3 Chinese strains and 1 Korean strain in the database, far away from the strains of other countries. Conclusion: The outbreak is caused by a single clone of Shigella sonnei, which are low virulence strains and have multiple drug resistance.

Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors / 中华肿瘤杂志

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

Screening strategies for quorum sensing inhibitors in combating bacterial infections / 药物分析学报

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.