AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

Objective To compare the influence between self-monitoring of blood gluocose(SMBG)combined with digital diabetes management and traditional management mode on the related clinical indexes in the patients with type 2 diabetes mellitus(T2DM).Methods A total of 100 patients with T2DM treated in the endocrinology and metabolism outpatient department of this hospital from January 2022 to June 2022 and meeting the inclusion criteria of this study were successively included.They were divided into the experimental group and control group.The experimental group was managed by SMBG combined with digital diabetes man-agement mode,while the control group adopted the traditional management mode,the outpatient clinic follow up once a month.After 6 months of follow-up,fasting blood glucose,glycosylated hemoglobin(HbA1c),low density lipoprotein cholesterol(LDL-C)and urinary microalbumin/creatinine ratio(UACR)were compared between the two groups.Results The FBG,HbA1c,LDL-C,and UACR of the experimental group decreased after intervention when compared with baseline.Compared with the control group,the FBG[8.7(7.7,9.2)mmol/L vs.10.8(8.8,12.7)mmol/L,Z=-4.660,P＜0.001],HbA1c[6.3％(5.3,7.8)％vs.8.5％(7.2,10.0)％,Z=-5.130,P＜0.001],LDL-C[2.6(1.8,3.1)mmol/L vs.3.3(2.6,4.0)mmol/L,Z=-4.112,P＜0.001],UACR[16.1(3.5,46.5)mg/g vs.58.4(11.9,108.0)mg/g,Z=-2.220,P=0.026]for patients in the expriemental group after intervention were significantly decreased.Conclusion SMBG combined with digital diabetes management model can significantly improve the clinical indicators of patients.

Objective:To evaluate the interaction between remimazolam and propofol for sedation during hysteroscopy.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 20-45 yr, with body mass index of 18-28 kg/m 2, scheduled for elective hysteroscopy, were included. The test was conducted in two steps. Up-and-down sequential allocation was used to determine the median effective dose (ED 50) of remimazolam (group A) and propofol (group B). The ED 50 obtained in A and B groups were then used as the standard to determine the combination regimen in group C (0.25×ED 50 of remimazolam+ 0.75×ED 50 of propofol as the initial dose), in group D (0.5×ED 50 of remimazolam+ 0.5×ED 50 of propofol as the initial dose), and in group E (0.75×ED 50 of remimazolam+ 0.25×ED 50 of propofol as the initial dose). Up-and-down sequential allocation was used to determine the ED 50 of propofol when propofol and remimazolam were combined in C, D and E groups. The interaction between the sedative effects of two drugs was analyzed using the isobolographic analysis method, and the interaction coefficient and synergistic dose ratio of two drugs were calculated. Results:The ED 50 of remimazolam was 0.180 mg/kg in group A, and the ED 50 of propofol was 1.167 mg/kg in group B. The results of isobolographic analysis showed that remimazolam and propofol had a synergistic effect. When remimazolam 0.045, 0.090 and 0.135 mg/kg were combined with propofol 0.546, 0.288 and 0.160 mg/kg, the interaction coefficients were 1.393, 1.339 and 1.127 respectively. The synergistic dosage ratio of remimazolam and propofol was 1.0∶(3.2 to 12.0). Conclusions:Remimazolam and propofol have a synergistic effect on sedation when used for hysteroscopy, and the dose ratio is 1.0∶(3.2-12.0).

Recent studies have demonstrated that bitter taste receptors are distributed not only in oral cavity but also in non-gustatory systems,such as the respiratory,digestive,reproductive and cardiovascular systems.The physiological role of bitter taste receptors is to recognize bitter substances or bacterial secretions,to trigger the immune response and to maintain the internal environmental homeosta-sis.In addition,oral bitter taste receptors are expressed not only in taste buds,perceiving bitter taste,but also in many other parts of periodontal tissues,which is the potential treatment target for oral infectious diseases.This review summarized the expression and distri-bution of oral bitter taste receptors which was off the taste buds and their roles in regulating oral inflammation and oral bacteria,dis-cussed the effects of genetic polymorphism of bitter taste receptor 38 subtype(TAS2R38)on innate immunity and its relationship with the susceptibility of dental caries and periodontal,aimed to provide novel ideas for the better prevention and treatment of dental caries and periodontal diseases.

Objective:To discuss the effect of fluid resuscitation on the occurrence of ferroptosis in vascular tissue and the structure of vascular cells in the rats with blast injury complicated with hemorrhagic shock,and to clarify its mechanism.Methods:A total of 54 healthy adult SD rats were randomly divided into normal group,blast injury complicated with hemorrhagic shock(model)group,and the fluid resuscitation(treatment)group,and there were 18 rats in each group.Among them,10 rats were randomly selected to observe the surival status and another 8 rats were selected to detect the other indexes.The average survival time(ST),24 h and 72 h survival rates of the rats in various groups were observed;the blood pressure(BP),heart rate(HR),and respiratory rate(RR)of the rats in various groups were observed;the levels of serum creatinine(Scr),blood urea nitrogen(BUN),lactate(LAC),glucose(GLU),iron ions,glutathione(GSH),and malondialdehyde(MDA)and the activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)in serum of the rats in various groups were detected;Western blotting method was used to detect the expression levels of ferroptosis marker proteins glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and heme oxygenase 1(HO-1)proteins in superior mesenteric artery tissue of the rats in various groups;the pathomorphology of the superior mesenteric artery of the rats in various groups was observed.Results:All the rats in normal group survived for 72 h,while the longest ST of the rats in model group did not exceed 9 h.Compared with model group,the ST and 24 h survival rate(SR)of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the BP,HR,and RR of the rats in model group were significantly decreased(P＜0.01).Compared with model group,the BP,HR,and RR of the rats in treatment group were significantly increased after fluid resuscitation(P＜0.05).Compared with normal group,the activities of AST and ALT,and the levels of Scr and BUN in serum of the rats in model group were significantly increased(P＜0.01).Compared with model group,the serum levels of LAC and GLU of the rats in treatment group were significantly decreased(P＜0.01).Compared with normal group,the concentration of iron ion,GSH level,MDA level,LDH activity in serum of the rats in model group were significantly increased(P＜0.05);compared with model group,the concentration of iron ion and LDH activity in serum of the rats in treatment group was significantly decreased(P＜0.01).Compared with normal group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in model group were significantly decreased(P＜0.05);compared with model group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in model group was increased(P＜0.01);compared with model group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in treatment group was increased(P＜0.01).The microscopic pathology results showed that the cell arrangement in the layers of the superior mesenteric artery tissue of the rats in model group was disordered,the swelling was significant and the thickness was increased;the pathological changes in superior mesenteric artery tissue of the rats in treatment group was alleviated.The ultramicroscopic pathology results showed that the endothelial cell structure of blood vessels of the rats in normal group was intact,and there was no swelling in the subendothelial matrix;the vascular endothelial cell membrane of the rats in model group was damaged,there were cytoplasmic dissolution and fragmentation,and the swelling of the subendothelial matrix was significant;the swelling of the vascular endothelial cells in treatment group was alleviated.Conclusion:Ferroptosis occurs in vascular tissue of the rats with blast injury complicated with hemorrhagic shock,and fluid resuscitation can alleviate the structural damage of the vascular cells by inhibiting the vascular tissue ferroptosis.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective    To study the feasibility and safety of CT-guided preoperative Hookwire localization of pulmonary nodules in clinical application. Methods    Clinical data of 102 patients who were scheduled to undergo surgical treatment for pulmonary nodules from June 2015 to April 2020 in the North Ward of Thoracic Surgery Department of Ruijin Hospital were retrospectively analyzed. There were 38 males and 64 females, aged 23-82 (53.2±12.8) years. Results    All 102 patients with pulmonary nodules underwent CT-guided preoperative Hookwire localization successfully, with a localization success rate of 100.0%. The localization time was 27.0 (11-67) min; the number of times to adjust the angle during the positioning process was 6.9 (3-14); the needle depth of the positioning needle was 41.5 (16.3-69.1) mm. A total of 48 (47.1%) patients had a small amount of bleeding in the lung tissue in the positioning area after positioning; 53 (51.9%) patients had a small amount of pneumothorax after positioning; 16 (15.7%) patients were found that the positioning needle completely shedded from the lung tissue in the subsequent surgery. One patient was transferred to open thoracotomy because of extensive dense adhesion in the thorax, and the remaining 101 patients were operated on under thoracoscopy. Postoperative pathology showed that 5 (4.9%) patients were adenocarcinoma in situ, 28 (27.5%) were microinvasive adenocarcinoma, 36 (35.3%) patients were invasive carcinoma and 32 (31.3%) patients were benign lesions. No patients had complications or adverse events related to preoperative positioning. Conclusion    Pre-operative CT-guided localization of Hookwire intrapulmonary nodules is safe and effective, and can meet the intraoperative localization needs of thoracic surgeons in most clinical situations, and is not inferior to other preoperative localization methods currently used in clinics.

Objective To analyze the infection situation of Helicobacter pylori (Hp) and its correlation with pepsinogen (PG) in the 60~80 year old population in Jianye District, Nanjing City. Methods From December 2018 to December 2020, 758 elderly people aged 60 to 80 in the community in Jianye District Nanjing City. were selected. All subjects were tested for Hp by 13C-UBT method, and clinical signs of Hp positive people aged 60 to 80 years were analyzed. Including gender, age, alcohol consumption, family history of stomach cancer, chronic gastritis, and spicy eating habits; Hp positive group was given amoxicillin capsule 1.0g/ time, twice a day, esomeprazole magnesium enteric-coated tablet 20mg/ time, twice a day, clarithromycin tablet 0.5g/ time, twice a day for 8 weeks, and Hp was detected again after the end of treatment. All levels of PGI, PGII and PGI/PGII were determined by ELISA. The serum PG level of the experimental group and the control group and the serum PG level of the Hp positive population before and after Hp eradication were compared, and the correlation between Hp infection and PG level in the elderly population was analyzed by Pearson correlation. Results A total of 161 cases (21.24%) of 758 patients with chronic gastritis had Hp infection. The proportion of Hp infection in males was significantly higher than that in females (χ²=4.128，P<0.05). The proportion of Hp infection in 70-80 years was higher than that in 60-69 years(χ²=6.771, P<0.05). The proportion of Hp infection in drinking elderly was higher than that in non-drinking elderly (χ² =8.305，P<0.05). The proportion of Hp infection in the elderly with family history of gastric cancer was higher than that in the elderly without family history of gastric cancer (χ²=6.169，P<0.05). The proportion of Hp infection in elderly patients with chronic gastritis was higher than that in patients without chronic gastritis (χ²=5.576 , P<0.05). The proportion of Hp infection in the elderly with spicy diet was higher than that in the non-spicy diet group(χ²=7.936, P<0.05). The levels of PGI and PGI/PGII in the experimental group were significantly higher than those in the control group (P<0.05). The level of PGII in experimental group was significantly lower than that in control group (P<0.05). After treatment, 76 hP-positive patients turned negative, and PGI and PGI/PGII levels after Hp eradication were significantly lower than those before Hp eradication (P<0.05). PGII after Hp eradication was significantly higher than before (P<0.05). According to Pearson correlation analysis, Hp infection in elderly population was positively correlated with PGI and PGI/PGII levels, with correlation coefficients (r1=0.408,r2=0.412,P<0.05), and negatively correlated with PGII, with correlation coefficients (r=-0.469, P<0.05). Conclusions The Hp infection rate in patients with chronic gastritis is high, mainly in elderly men in Jianye District, Nanjing City.The levels of PGI and PGII in HP-positive patients are high, and the levels of PGI/PGII are low. The serum PG level can be used to evaluate the diagnosis and treatment effect of patients with Hp infection.

Objective:To evaluate clinical efficacy and safety of secukinumab in the treatment of erythrodermic psoriasis.Methods:From July 2019 to August 2021, 7 patients with erythrodermic psoriasis, who received subcutaneous injection of secukinumab at a dose of 300 mg once a week from week 0 to 4 followed by every-4-week dosing in Wuhan Hospital of Integrated Traditional Chinese and Western Medicine, were collected. At weeks 0, 4, 8 and 12, the psoriasis area and severity index (PASI) was recorded, and adverse drug reactions were observed.Results:All 7 patients were treated for at least 12 weeks. After 4-week treatment, 4 patients achieved PASI50; after 12-week treatment, 5 achieved PASI75, and 2 achieved PASI90. No serious adverse drug reactions occurred. One patient developed fever during the treatment, but the body temperature returned to normal after management; another 1 developed cough and expectoration, and the symptoms were relieved after oral administration of a Chinese herbal preparation named pharyngitis mixture.Conclusion:Secukinumab is effective in the treatment of erythrodermic psoriasis, with fewer adverse reactions, which provides a new option for the treatment of erythrodermic psoriasis.

OBJECTIVE：To study the effects of chitosan graphene oxide car rier（CS-GO）loaded with oridonin （CS-GO- oridonin）on the proliferation and apoptosis of human lung cancer A 549 cells. METHODS ：Taking A 549 cells as objects ，the survival rate of cells were detected by CCK- 8 method after treated with different concentrations of CS-GO （3，6，12，24，48 μg/mL）and CS-GO-oridonin loaded with same mass of oridonin （3，6，12，24，48 μg/mL，by the weight of oridonin ，the same below）. IC 50 of CS-GO-oridonin was calculated. The cell morphology were observed by microscope after treated with CS-GO and CS-GO-oridonin（both 32 μg/mL）for 2，4，10，24 h. The uptake of CS-GO ，oridonin，CS-GO-orionin（all 32 μg/mL）by cells was observed with fluorescence labeling method. The apoptosis of cells and the content of ROS were observed by flow cytometry after treated with different concentrations of CS-GO （16，32，64 μg/mL）and CS-GO-oridonin （16，32，64 μg/mL）. The expression of anti-apoptosis related proteins （Mcl-1，Bax and Bak ）were detected by Western blot. RESULTS ：After treated with different concentrations of CS-GO ，the survival rate of cells was still above 90％ ；after treated with different concentrations of CS-GO-oridonin，the survival rate of cells showed a downward trend ，and was significantly lower than that of CS-GO group （P＜ 0.01）；IC50 of CS-GO-oridonin was 32.61 μg/mL. After CS-GO treatment，the cell morphology did not change significantly ；after CS-GO-oridonin treatment ，the cells shrunk and fell off in clusters ，and the suspended matter increased ；the fluorescence of oridonin and CS-GO-orionin taken up by cells was enhanced than CS-GO. Compared with blank group ，there was no significant change in the apoptosis rate ，the content of ROS and the expression of apoptosis-related protein in 16，32，64 μg/mL CS-GO groups（P＞0.05）；apoptosis rate ，the content of ROS ，the protein expression of Bax and Bak in 16，32，64 μg/mL CS- GO-oridonin groups were increased significantly ，while the protein expression of Mcl- 1 were decreased significantly. Above indexes were significantly high er or lower than the same concentration CS-GO group （P＜0.05）. CONCL USIONS：CS-GO dose not affect the proliferation and apoptosis of A 549 cells；CS-GO-oridonin has obvious inhibition and apoptosis promoting effect on cells ，which may be related to increasing ROS production and regulating the expression of apoptosis related proteins.