Objective To investigate whether dexmedetomidine(DEX)can inhibit the inflammatory response mediated by microglia after traumatic brain injury(TBI)in rats through the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods A TBI rat model was constructed,and successfully modeled rats were randomly separated into TBI group,low and high-dose dexmedetomidine treatment groups(DEX-L,DEX-H groups),and high-dose dexmedetomidine treatment+cGAS-STING pathway activator group(DEX-H+DMXAA group),with 18 rats in each group.Additionally,18 healthy normal rats were selected as the Control group.Rats in each group were subjected to neurobehavioral scoring(mNSS).The brain water content of rats in each group was detected.Flow cytometry was used to detect Tregs in the brain tissue of each group.ELISA was applied to detect the levels of inflammatory cytokines in brain tissue.HE staining was applied to observe brain tissue injury.TUNEL staining was applied to detect neuronal apoptosis.Immunohistochemistry was applied to detect the expression of the microglial cell marker ion calcium binding adapter molecule 1(Iba1).Western blot was applied to detect the expression of apoptosis and cGAS-STING pathway related proteins.Results Compared with the Control group,the TBI group showed structural injury to brain tissue,edema,abnormal neuronal morphology,reduced number and disordered arrangement,deep staining of nuclear folds,and blurred nucleoli,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1 β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Compared with the TBI group,the brain tissue structure of the DEX-L and DEX-H groups was slightly injuried,edema was reduced,and the morphology of neurons was relatively normal,with a small decrease in number and relatively neat arrangement,a small amount of nuclei were wrinkled and deeply stained,and most of the nucleoli were obvious,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were reduced(P＜0.05).The brain tissue structure and neuronal injury in the DEX-H+DMXAA group were more severe than the DEX-H group,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Conclusion Dexmedetomidine can inhibit the inflammatory response mediated by microglia after TBI in rats,and its mechanism of action is related to the inhibition of the cGAS-STING pathway.

Objective To investigate whether dexmedetomidine(DEX)can inhibit the inflammatory response mediated by microglia after traumatic brain injury(TBI)in rats through the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods A TBI rat model was constructed,and successfully modeled rats were randomly separated into TBI group,low and high-dose dexmedetomidine treatment groups(DEX-L,DEX-H groups),and high-dose dexmedetomidine treatment+cGAS-STING pathway activator group(DEX-H+DMXAA group),with 18 rats in each group.Additionally,18 healthy normal rats were selected as the Control group.Rats in each group were subjected to neurobehavioral scoring(mNSS).The brain water content of rats in each group was detected.Flow cytometry was used to detect Tregs in the brain tissue of each group.ELISA was applied to detect the levels of inflammatory cytokines in brain tissue.HE staining was applied to observe brain tissue injury.TUNEL staining was applied to detect neuronal apoptosis.Immunohistochemistry was applied to detect the expression of the microglial cell marker ion calcium binding adapter molecule 1(Iba1).Western blot was applied to detect the expression of apoptosis and cGAS-STING pathway related proteins.Results Compared with the Control group,the TBI group showed structural injury to brain tissue,edema,abnormal neuronal morphology,reduced number and disordered arrangement,deep staining of nuclear folds,and blurred nucleoli,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1 β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Compared with the TBI group,the brain tissue structure of the DEX-L and DEX-H groups was slightly injuried,edema was reduced,and the morphology of neurons was relatively normal,with a small decrease in number and relatively neat arrangement,a small amount of nuclei were wrinkled and deeply stained,and most of the nucleoli were obvious,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were reduced(P＜0.05).The brain tissue structure and neuronal injury in the DEX-H+DMXAA group were more severe than the DEX-H group,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Conclusion Dexmedetomidine can inhibit the inflammatory response mediated by microglia after TBI in rats,and its mechanism of action is related to the inhibition of the cGAS-STING pathway.

Objective To investigate the 90%effective dose(ED90)of ciprofol combined with alfentanil in inhibiting gastroscopy insertion response in elderly patients.Methods 110 patients were selected to undergo painless gastroscopy examination on a scheduled basis.110 patients were randomly divided into ciprofol group alone(group H,n=57)and ciprofol group combined with alfentanil 5 μg/kg(group A,n=53).The trial was conducted according to the Biased coin design up-and-down(BCD-UDM)sequential.Patients in group H were given only intravenous infusion of ciprofol and patients in group A were pre-infused with intravenous alfentanil at 5μg/kg,followed by intravenous infusion of ciprofol,and gastroscopy was initiated when the modified observer's assessment of alertness/sedation scale(MOAA/S)was≤1 point.The initial dose of ciprofol was 0.200 mg/kg in all cases,and the adjacent isotropic dose was 0.030 mg/kg.If the patient's MOAA/S was still>1 or the patient had a response that interfered with the operative examination,such as choking or body movement,during gastroscopy placement,2.0 min after the intravenous infusion of ciprofol,was regarded as an ineffective response,then the next patient was elevated by one dose gradient.If the anesthetic effect of the previous patient was judged to be a valid response,the next patient was randomized to a dose according to the BCD-UDM,with an 11%(b=0.11)probability of decreasing the dose gradient by one dose,and an 89%(1-b=0.89)probability of remaining unchanged,and the experiment was terminated at the 45th effective response in each group.Probabilistic unit regression analysis was used to calculate the ED90,95%effective dose(ED95),and 95%confidence intervals(CI)for the inhibition of gastroscopy placement response with ciprofol alone and the combination of 5 μg/kg alfentanil in elderly patients.Results The ED90 of ciprofol in group A was 0.296 mg/kg(95%CI:0.275～0.338),and ED95 was 0.310 mg/kg(95%CI:0.291～0.383);The ED90 of ciprofol in group H was 0.407 mg/kg(95%CI:0.390～0.447),and ED95 was 0.420 mg/kg(95%CI:0.402～0.483).Compared with group H,the total amount of ciprofol was significantly reduced in group A,the time of awakening and time of leaving the hospital were significantly shorter,and the incidence of intraoperative hypotension and hypoxemia was significantly lower,the differences were statistically significant(P<0.05).Conclusion The ED90 of ciprofol combined with 5 μg/kg of alfentanil and ciprofol alone in inhibiting gastroscopy implantation in elderly patients are 0.296 mg/kg and 0.407 mg/kg respectively.

Objective:To investigate the association between plasma uric acid and hypertension and the gender difference in community-dwelling middle-aged and elderly population.Methods:A community-based cross-sectional study was conducted in Beijing Tongzhou Yongshun Community Health Service Center from June to December 2021, among residents aged 45 years or older selected by cluster sampling method. According to plasma uric acid (UA) level in quartiles, the subjects were divided into 4 groups; and stratified by gender, the subjects were further divided into subgroups. Multivariate logistic regression model was used to analyze the related factors of hypertension, and restricted cubic spline fitting logistic regression model was used to analyze the nonlinear association between uric acid and hypertension and the cut-off values of uric acid.Results:A total of 6 229 residents with the age of (63.2±7.3) years were enrolled in the study. In 1 874 male participants (30.1%), 946 participants (50.5%) had hypertension, and the uric acid level was 359 (309, 418)μmol/L; in 4 355 female participants (69.9%), 2 003 participants (46.0%) had hypertension, and the uric acid level was 306 (261, 359)μmol/L. Multivariate logistic regression analysis showed that after adjusting for factors that were statistically significant in univariate analyses or potentially clinically relevant (including age, body mass index, diabetes mellitus, coronary heart disease, cerebrovascular disease, albumin, estimated glomerular filtration rate, and cholesterol), uric acid was independently associated with hypertension ( P<0.001), for total participants the risk of hypertension in Q4 group was 1.33 times of that in Q1 group ( OR=1.33,95% CI 1.13-1.56, P=0.001); while for females the risk of hypertension in Q4 group was 1.38 times of that in Q1 group ( OR=1.38,95% CI 1.13-1.68, P=0.002), but no significant association was observed for males ( P>0.05). The results of restricted cubic spline fitting logistic regression analysis showed that there was a linear association between uric acid level and hypertension in the total population and males, and the risk of hypertension increased with uric acid level ( P<0.001 for the total population, P=0.016 for male). However, there was a non-linear association in females. When uric acid>307 μmol/L in females, the risk of hypertension increased significantly as the level of uric acid increased ( P<0.001). Conclusions:Uric acid level was independently associated with hypertension in the community-dwelling middle-aged and elderly population, and there was a gender difference in the correlation. The association was nonlinear in females and the cut-off value of uric acid in females was 307 μmol/L.

Objective:To conduct a scoping review of studies on the development and validation of web-based decision aids for fertility protection in cancer patients, so as to provide references for related studies.Methods:Using the Joanna Briggs Institute scoping review guideline as the methodological framework, PubMed, Web of Science, Embase, CINAHL, Cochrane Library, CNKI, Wanfang Database, VIP and China Biomedical Literature Database were searched. The search deadline was from the establishment of the databases to December 1, 2022.Results:A total of 16 articles were included, involving 12 web-based decision aids for cancer patient fertility protection. The basic information, tool content, development, validation and evaluation indicators of the included articles were summarized and analyzed.Conclusions:Future research should provide personalized decision support based on patient needs, comprehensively reference mature international theories or frameworks, promote systematization and transparency in the development of decision support tools, and improve the validation system of tools to improve their quality.

OBJECTIVE: To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A (MPS Ⅲ A). METHODS: A female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site. RESULTS: The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range. CONCLUSION The compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.
Female ; Humans ; Cardiomyopathy, Hypertrophic ; Contrast Media ; East Asian People ; Gadolinium ; Mucopolysaccharidosis III ; Mutation ; Pedigree ; Male ; Middle Aged

Objective:To evaluate the effect of pectoral nerve block type Ⅱ combined with esketamine on anxiety and depression in the patients with breast cancer undergoing modified radical mastectomy under general anesthesia.Methods:Eighty-four female patients, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18-25 kg/m 2, undergoing elective first-time modified radical mastectomy for unilateral breast cancer, were divided into 2 groups ( n=42 each) using a random number table method: routine group (R group) and pectoral nerve block type Ⅱ combined with esketamine group (PS group). Sufentanil was used for anesthesia induction and postoperative patient-controlled intravenous analgesia (PCIA) in group R, esketamine was used for anesthesia induction and postoperative PCIA, and type Ⅱ thoracic nerve block was performed under ultrasound guidance after anesthesia induction in group PS, and the rest of the drugs used were the same in both groups.The observer′s assessment of awareness/sedation scale score was recorded at the end of surgery, 30 min after the end of surgery, and at 6, 12 and 24 h after surgery.The Hospital Anxiety and Depression Scale was used to assess patients′ anxiety and depression at 1 day before surgery and at discharge.The intraoperative consumption of anesthetics, emergence time, postanesthesia care unit stay time, pressing times of PCIA, requirement for rescue analgesia, hospital costs, length of postoperative hospital stay, satisfaction scores of surgeons and patients were recorded at discharge.The occurrence of adverse reactions was also recorded after operation. Results:Compared with group R, the observer′s assessment of awareness/sedation scale score were significantly increased at the end of surgery and 30 min after surgery, the consumption of propofol and remifentanil was decreased, the emergence time and postanesthesia care unit stay time were shortened, the incidence of nausea and vomiting was decreased, the Hospital Anxiety and Depression Scale score was decreased at discharge, the incidence of anxiety and depression was decreased, the satisfaction scores of surgeons and patients were increased, and the length of postoperative hospital stay was shortened in group PS ( P<0.05). Conclusions:Pectoral nerve block type Ⅱ combined with esketamine can optimize the efficacy of anesthesia and relieve early postoperative anxiety and depression in the patients undergoing modified radical mastectomy for breast cancer under general anesthesia.

Objective:To evaluate the effect of health education of a three-year special action for prevention and control of drinking water-borne endemic fluorosis (referred to as drinking water-borne fluorosis) in Shandong Province, and to provide basis for formulating health education measures in the next step.Methods:Nineteen of the disease affected counties (cities and districts) were selected as project counties (cities and districts) in key areas for prevention and control of drinking water-borne fluorosis in Shandong Province in 2018, and 50 disease affected counties (cities and districts) were selected in 2019, and the project counties (cities and districts) were expanded to all of the 105 disease affected counties (cities and districts) in Shandong Province in 2020. Three disease affected townships (towns) were selected in each county (city and district), and health education activities on drinking water-borne fluorosis were carried out in Grade 4 to Grade 6 of the central primary schools and the three villages under its jurisdiction. Students and housewives were selected to conduct questionnaire surveys on prevention and control knowledge of drinking water-borne fluorosis before and after health education. The incidence of dental fluorosis among children aged 8 - 12 years was investigated annually in 6 villages (with children aged 8 - 12 years > 50) , where health education activity was implemented and the incidence of dental fluorosis among children was > 30%, water fluoride content was > 1.5 mg/L and water improvement time was < 5 years.Results:After health education, the awareness rates of drinking water-borne fluorosis in fifth grade pupils [92.46% (4 571/4 944) vs 65.80% (3 334/5 067) in 2018; 94.84% (12 897/13 599) vs 73.55% (9 993/13 587) in 2019; 95.59% (30 407/ 31 809) vs 77.52% (24 463/31 557) in 2020] and housewives [94.12% (2 400/2 550) vs 76.04% (1 939/2 550) in 2018; 94.99% (6 412/6 750) vs 72.00% (4 860/6 750) in 2019; 95.53% (16 183/16 941) vs 78.43% (12 971/16 539) in 2020] were significantly improved (χ 2 = 1 070.47, 2 315.27, 4 456.40, 328.25, 1 294.80, 2 174.63, P < 0.05). After health education in 2020, there were significant differences in the correct answer rates of epidemic causes, hazards and preventive measures of drinking water-borne fluorosis in the questionnaire of fifth grade pupils and housewives (χ 2 = 390.78, 164.94, P < 0.05). The awareness rates of drinking water-borne fluorosis in fifth grade pupils and housewives in the eastern region (Qingdao City, Yantai City and Weifang City) were significantly higher than those in the western region (Dezhou City, Liaocheng City and Heze City) before health education (χ 2 = 547.43, 210.12, P < 0.05), and after health education, the awareness rates increased to more than 90%. The detection rate of dental fluorosis in children decreased year by year (χ 2trend = 27.95, P < 0.05). Conclusions:Through implementation of a three-year special action for prevention and control of drinking water-borne fluorosis in Shandong Province, the awareness rate of fluorosis among target populations has been significantly improved. However, it is still necessary for government departments to further increase investment in health education and carry out health education activities in a deep-going way.

Transcranial direct current stimulation (tDCS) is a well-tolerated, safe and noninvasive physical brain stimulation method, which has been widely used in the treatment of some common mental disorders and neurological diseases and has achieved certain clinical effects. It is necessary to develop expert consensus on clinical treatment to improve the use norms in related fields. According to the clinical research published before August 2021 and the method of evidence-based medicine, we published an expert consensus on tDCS in the treatment of depressive disorders, schizophrenia, substance use-related disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, anxiety disorders, post-traumatic stress disorder, sleep disorders, pain, Parkinson′s disease, stroke, and epilepsy. The consensus also introduced the safety and efficacy of the clinical use of tDCS, and standardized the treatment process and operation technology, aiming to provide guidance for the clinical application of tDCS and promote the standardized development of this treatment technology in the future.

Transcranial direct current stimulation (tDCS) is a well-tolerated, safe and noninvasive physical brain stimulation method, which has been widely used in the treatment of some common mental disorders and neurological diseases and has achieved certain clinical effects. It is necessary to develop expert consensus on clinical treatment to improve the use norms in related fields. According to the clinical research published before August 2021 and the method of evidence-based medicine, we published an expert consensus on tDCS in the treatment of depressive disorders, schizophrenia, substance use-related disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, anxiety disorders, post-traumatic stress disorder, sleep disorders, pain, Parkinson′s disease, stroke, and epilepsy. The consensus also introduced the safety and efficacy of the clinical use of tDCS, and standardized the treatment process and operation technology, aiming to provide guidance for the clinical application of tDCS and promote the standardized development of this treatment technology in the future.