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 observe the improved effect of propofol on vascular hyporeactivity in septic rats and its underlying mechanism.Methods A total of 96 SD rats(12 weeks old,both genders,weighing 200～220 g)were randomly divided into sham group(n=16),sepsis group(n=16,cecal ligation and puncture),propofol group(n=16),propofol+ROCK inhibitor Y-27632 group(n=16),propofol+PKCαinhibitor GO6976 group(n=16),propofol+IP3 inhibitor 2-APB group(n=8)and propofol+gap junction inhibitor metoclopramide sodium(Movens)group(n=8).In vitro vascular ring reactivity and vascular calcium sensitivity were measured to observe the improved effects of propofol on vascular hyporeactivity in septic rats and its relationships with RhoA/ROCK,PKCα,IP3 and cell gap junction.Results Determination of in vitro vascular ring and calcium sensitivity showed that the contractile reactivity to norepinephrine(NE)and to calcium sensitivity were significantly decreased in the arterial rings isolated from the septic rats compared with those from the sham group,with the dose-response curve shifting to the right,and most significant decrease by 51.42％in the superior mesenteric artery(SMA,P＜0.05).Propofol treatment significantly improved the hyporeactivity and calcium sensitivity of the vessels isolated from the septic rats,especially those of the femoral artery with a recovery rate of 89.57％(P＜0.05).In comparison with the propofol group,the dose-response curves of the propofol+Y-27632 group and the propofol+GO6976 group were shifting to right,indicating that Y-27632 and GO6976 could significantly inhibit the amelioration of propofol on calcium sensitivity of SMA in severely septic rats with an inhibitory rate of 146.95％and 88.63％(P＜0.05),respectively.Isolated vascular reactivity measurement demonstrated that Y-27632 and Movens treatment significantly antagonized the ameliorated role of propofol on hyporeactivity of blood vessels from the septic rats with an inhibitory rate of 40.79％and 169.90％(P＜0.05),separately,while no such effect was observed in the propofol+GO6976 and propofol+2-APB groups.Conclusion Propofol treatment can significantly improve vascular hyporeactivity of septic rats,which may attribute to the increase of vascular calcium sensitivity through RhoA/ROCK pathway.

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.

Objective:To study the changing trend of brucellosis epidemic in Taiyuan City, Shanxi Province from 2004 to 2022, and to provide reference for formulating brucellosis prevention and control policies.Methods:Through the China Disease Prevention and Control Information System, the epidemic data of human brucellosis with the onset time from January 1, 2004 to December 31, 2022 and the current address in Taiyuan City were collected. Descriptive epidemiological methods were used to analyze the temporal, regional, and population distribution characteristics of brucellosis.Results:From 2004 to 2022, a total of 1 834 cases of brucellosis were reported in Taiyuan City, with an average annual incidence rate of 2.25/100 000. The incidence rate of brucellosis in each year showed a fluctuating upward trend (χ 2trend = 428.04, P < 0.001). The onset time was mainly concentrated from February to August, accounting for 76.94% (1 411/1 834) of the total cases, with May being the peak month (283 cases). The incidence rate of brucellosis in all counties (cities and districts) ranged from 0 to 38.37/100 000, with the highest incidence rate in Loufan County in 2021. There were 1 470 males and 364 females, with a male-to-female ratio of 4.04 ∶ 1.00. The age range was 1 to 95 years old, among which the 1 - 29 age group accounted for 14.29% (262/1 834), the 30 - 39 age group accounted for 13.14% (241/1 834), the 40 - 49 age group accounted for 21.05% (386/1 834), the 50 - 59 age group accounted for 27.54% (505/1 834), and the 60 - 95 age group accounted for 23.99% (440/1 834). The main occupation was farmers and herdsmen, accounting for 67.23% (1 233/1 834). Conclusion:From 2004 to 2022, the epidemic of brucellosis in Taiyuan City shows a fluctuating upward trend, with males, middle-aged and elderly people, and farmers and herdsmen as the main affected population.

Injury monitoring is an important approach for injury control and is an important part of comprehensive disease monitoring. With the development of medical digitalization, an intelligent injury monitoring system has been created in Yinzhou District, Ningbo City, Zhejiang Province using artificial intelligence techniques based on Ningbo Municipal Health Information Platform and has been applied across the district since 2019. The manual card-reporting mode has been transformed to intelligent card-reporting mode in this system, which achieves functions of epidemiological analyses of the monitoring data, early warning of high-incidence injuries, classified management of injury and quality control of report cards. Nearly 300 thousand cards have been automatically reported since the system was online available since November 2022, and the epidemiological characteristics of injury were preliminarily understood, which provide data supports to early earning and interventions of injury. The intelligent injury monitoring system greatly improves the injury monitoring efficiency and card-reporting quality, and saves a large number of manpower and material resources, which provides a powerful technical support to widespread injury monitoring.

Objective To investigate the association between gallstones (GS) and metabolic syndrome (MS) in southern Xinjiang, China, and to provide experience for the prevention and control of metabolic diseases in southern Xinjiang. Methods The patients with GS who visited First Division Hospital, Second Division Korla Hospital, and Third Division Hospital of Xinjiang Production and Construction Corps from March 2015 to March 2019 were enrolled as case group, and cluster sampling was used to select the individuals who underwent physical examination in Third Division 51st Regiment Hospital during the same period of time were enrolled as control group. According to inclusion and exclusion criteria, 1140 cases were enrolled in each group after 1∶ 1 matching based on age and sex. The t -test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for GS. Dummy variables were included by logistic regression to evaluate multiplicative interaction between MS components, and the parameter estimate and covariance matrix of the logistic regression model and interaction calculation table were used to calculate and evaluate additive interaction between MS components. Results The risk of GS in MS patients was 2.33 times that in non-MS patients (odds ratio [ OR ]=2.33, 95% confidence interval [ CI ]: 1.86-2.92). In addition, the components of MS also increased the risk of GS, including blood glucose ( OR =2.94, 95% CI : 2.36-3.68), blood pressure ( OR =1.50, 95% CI : 1.26-1.80), blood lipids ( OR =1.48, 95% CI : 1.25-1.75), and body mass index ( OR =1.44, 95% CI : 1.21-1.70). After adjustment for multiple factors, the risk of GS gradually increased with the increase in the number of metabolic abnormalities, i.e., one abnormality ( OR =1.55, 95% CI : 1.22-1.99), two abnormalities ( OR =2.13, 95% CI : 1.66-2.72), three abnormalities ( OR =3.48, 95% CI : 2.59-4.69), and four abnormalities ( OR =4.65, 95% CI : 2.79-7.84). No additive or multiplicative interaction was found between MS components. Conclusion GS is closely associated with MS in southern Xinjiang, and the risk of GS gradually increases with the increase in MS components. No additive or multiplicative interaction is found between GS and MS components.

Objective:To investigate the application value of endoscopic ultrasound (EUS) in tumor staging of adenocarcinoma of the esophagogastric junction (AEG) after neoadjuvant concurrent chemoradiotherapy.Methods:The clinical data of 40 patients diagnosed with stage Ⅲ AEG and treated with neoadjuvant concurrent chemoradiotherapy from January 2016 to December 2021 in the First Affiliated Hospital of Hebei North University were retrospectively analyzed. EUS was used to perform preoperative tumor staging after neoadjuvant concurrent chemoradiotherapy to evaluate the therapeutic effect, and the consistency between EUS and postoperative pathological staging was analyzed.Results:In 40 AEG patients after neoadjuvant chemoradiotherapy, the EUS staging was stage yp-uT 2 in 12 cases, stage yp-uT 3 in 18 cases, and stage yp-uT 4 in 10 cases. The postoperative pathological staging was stage pT 1 in 2 cases, stage pT 2 in 14 cases, stage pT 3 in 12 cases, and stage pT 4 in 12 cases. Taking postoperative pathological results as the gold standard, the accuracy of EUS for T staging after neoadjuvant chemoradiotherapy was 62.5%, and the accuracy, sensitivity and specificity for stage T 2 were 58.3%, 50.0% and 80.8%, respectively. The accuracy, sensitivity and specificity for stage T 3 were 61.1%, 91.7% and 75.0%, respectively. The accuracy, sensitivity and specificity for stage T 4 were 70.0%, 58.3% and 89.3%, respectively. The Kappa value of the consistency test between yp-uT staging and pT staging was 0.453. The EUS staging of lymph nodes was stage yp-uN 0 in 15 cases, stage yp-uN 1 in 10 cases, stage yp-uN 2 in 10 cases, and stage yp-uN 3 in 5 cases. The postoperative pathological staging was stage pN 0 in 18 cases, stage pN 1 in 7 cases, stage pN 2 in 7 cases, and stage pN 3 in 8 cases. Taking postoperative pathological results as the gold standard, the accuracy rate of EUS for N staging after neoadjuvant chemoradiotherapy was 57.5%, and the accuracy, sensitivity and specificity of EUS for stage N 0 were 73.3%, 61.1% and 81.8%, respectively. The accuracy, sensitivity and specificity for stage N 1 were 50.0%, 71.4% and 84.8%, respectively. The accuracy, sensitivity and specificity for stage N 2 were 40.0%, 57.1% and 81.8%, respectively. The accuracy, sensitivity and specificity for stage N 3 were 60.0%, 37.5% and 93.8%, respectively. The Kappa value of the consistency test between yp-uN staging and pN staging was 0.409. Conclusions:EUS is not accurate for T staging in patients with stage Ⅲ AEG after neoadjuvant therapy, but has high sensitivity for stage T 3 and high specificity for stage T 4. EUS has low sensitivity for N staging in patients with stage Ⅲ AEG after neoadjuvant therapy, but has high specificity for stage N 3.

Objective:To examine the efficacy and safety of third-party bone marrow-derived mesenchymal stem cells (MSCs) in the treatment of refractory delayed hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Twenty patients with refractory LOHC received conventional therapy combined with MSCs obtained from third-party donors’ bone marrow (BM) . MSCs were given intravenously at a dose of 1 × 10 6 cells/kg once weekly until either the symptoms improved or no changes in LOHC were seen after continuous infusion four times. BK viruria (BKV) -DNA, JC viruria (JCV) -DNA, and CMV-DNA were detected by real-time quantitative PCR before and 8 weeks after the MSCs infusion. Results:① Of the 20 patients with refractory LOHC, 15 were males, and 5 were females, and the median age was 35 (15-56) years. There were 5 cases of acute lymphoblastic leukemia (ALL) , 9 cases of acute myeloid leukemia (AML) , 5 cases of myelodysplastic syndrome (MDS) , and 1 case of maternal plasma cell like dendritic cell tumor (BPDCN) . There were 4 cases of HLA identical transplantation and 16 cases of HLA incomplete transplantation. ②The median number of MSC infusions for each patient was 3 (range: 2-8) . Seventeen patients achieved complete response, and one had a partial response after treatment. The overall response rate was 90%. Over a median follow-up period of 397.5 days (range 39-937 days) post-transplantations, 13 patients survived, and 7 died. The causes of death included aGVHD (1 case) , infections (5 cases) , and TMA (1 case) . ③The copy numbers of BKV-DNA and CMV-DNA in urine in the 8th week after MSCs infusion were significantly lower than those observed before treatment (11342.1×10 8 copies/L vs 5.2×10 8 copies/L, P=0.016; 3170.0×10 4 copies/L vs 0.2×10 4 copies/L, P=0.006, respectively) , while JCV-DNA did not significantly differ when compared to before treatment ( P=0.106) . ④ No adverse reactions related to MSC infusion occurred in any of the 20 patients. Conclusion:Third-party bone marrow-derived MSC has significant efficacy and good safety in the treatment of refractory LOHC after allogeneic HSCT.

OBJECTIVE: To explore the role of small nuclear noncoding RNA 7SK in embryonic stem cell (ESCs) proliferation and the value of 7SK as a target for early diagnosis and treatment for primordial dwarfism (PD). METHODS: ESC line R1 was transfected with the CRISPR/Cas9 system, and sequencing of the PCR product and glycerol gradient analysis were performed to identify novel 7SK deletion mutations. A lentivirus system was used to knock down cyclin-dependent kinase 9 (CDK9) in clones with 7SK deletion mutations, and the effect of CDK9 knockdown on the protein level of cell division cycle 6 (CDC6) was analyzed with Western blotting. RESULTS: We identified a novel deletion mutation of 7SK at 128-179 nt in the ESCs, which resulted in deficiency of cell proliferation. 7SK truncation at 128-179 nt significantly reduced the protein expressions of La-related protein 7 (LARP7) and CDC6. CONCLUSIONS 7SK truncation at 128-179 nt can significantly impair proliferation of ESCs by downregulating CDC6. 7SK is a key regulator of proliferation and mediates the growth of ESCs through a mechanism dependent on CDK9 activity, suggesting the value of 7SK truncation at 128-179 nt as a potential target for early diagnosis and treatment of PD.
Cell Cycle Proteins ; Cell Proliferation ; Embryonic Stem Cells/metabolism* ; HeLa Cells ; Humans ; Nuclear Proteins ; Positive Transcriptional Elongation Factor B/metabolism* ; RNA, Long Noncoding/genetics* ; RNA-Binding Proteins ; Ribonucleoproteins ; Transcription Factors

Objective:To investigate the status of removing iodized salt, water iodine, and iodine nutrition of children in water source high iodine areas in Taiyuan City, Shanxi Province, so as to provide basis for the implementation of prevention and control measures in high iodine areas according to local conditions.Methods:From 2012 to 2017, four administrative villages were selected from each of the high iodine townships in the water source high iodine areas (Qingxu County and Xiaodian District) in Taiyuan City, and 15 households in each administrative village were sampled for salt iodine detection by semi quantitative method. According to the "National Monitoring Program for Water Source High Iodine Areas (Trial)" (2012 edition), 1-2 high iodine villages were selected respectively in Qingxu County and Xiaodian District every year as monitoring sites, and grouped by water iodine of 150-300 μg/L and > 300 μg/L. If the monitoring site had been implemented the water improvement project, one tap water sample shall be collected. Whereas, if the monitoring site had not been implemented the water improvement project, two drinking water samples shall be collected from each household in the five directions of east, west, south, north and middle, and the water iodine shall be detected using the "Research on Methods for Water Iodine Testing in Iodine Deficiency and High Iodine Areas" recommended by the National Iodine Deficiency Disorders Reference Laboratory of the Chinese Center for Disease Control and Prevention. A total of 100 children aged 8-10 years old were selected from village primary schools or central primary schools in townships where the monitoring sites were located, and their thyroid volume was detected by B-ultrasound; urine samples were taken from more than 30 children and urinary iodine was detected by arsenic-cerium catalytic spectrophotometry.Results:From 2012 to 2017, the rate of non-iodized salt in Qingxu County ranged from 91.7% (165/180) to 96.1% (173/180); the rate of non-iodized salt in Xiaodian District were all 100.0% (120/120). A total of 52 water samples were tested, and the median water iodine was 282.3 μg/L, ranged from 121.1 to 546.3 μg/L. A total of 1 401 children's thyroid were examined, and the goiter rate was 7.5% (105/1 401). A total of 597 children's urine samples were tested, and the median urinary iodine was 458.1 μg/L, ranged from 21.0 to 1 778.7 μg/L. The median urinary iodine (327.1 μg/L) and goiter rate (4.9%, 34/697) of children in the 150-300 μg/L water iodine group were compared with those in the > 300 μg/L water iodine group (552.9 μg/L; 10.1%, 71/704), the differences were statistically significant ( Z = - 8.934, χ 2 = 13.698, P < 0.01). Conclusions:From 2012 to 2017, the median water iodine is 282.3 μg/L in water source high iodine areas in Taiyuan City, the status of removing iodized salt is good (the rate of non-iodized salt > 90%). However, children have excessive iodine (median urinary iodine ≥300 μg/L) and goiter rate (> 5%). It is suggested that the main measures should be taken to improve water quality and reduce iodine content in drinking water in water source high iodine areas, continuously monitor water iodine, and timely adjust the prevention and control measures according to the change of water iodine.