Objective To explore the correlation between neutrophil-to-lymphocyte ratio(NLR)and Behcet's disease(BD)activity.Methods A total of 103 BD patients were divided into the low activity group(0-4,61 cases)and the high activity group(5-11,42 cases)according to electronic medical record-based disease activity index(EMRAI)score.The white blood cell(WBC),neutrophil(NEU),lymphocyte(LY),platelet(PLT),red blood cell(RBC),hemoglobin(Hb),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),IgG,IgA,IgM,complement C3 and C4 were detected.NLR and platelet-to-lymphocyte ratio(PLR)were calculated.The correlation between NLR,PLR and ESR,CRP,EMRAI were analyzed.Logistic regression was used to analyze the influencing factors of BD disease activity.Receiver operating characteristic(ROC)curve was drawn to evaluate the effectiveness of NLR in judging BD disease activity.Results WBC,NEU,PLT,ESR,CRP,NLR,PLR,complement C3 and C4 in patients were higher in the high activity group than those in the low activity group(P＜0.05),and there were no significant differences in other indexes(P＞0.05).NLR was positively correlated with ESR,CRP and EMRAI in the whole group,while PLR was positively correlated with ESR,CRP and EMRAI in the whole group(P＜0.05).Logistic regression analysis showed that high NLR was a risk factor for BD disease activity(OR=1.511,95%CI:1.080-2.113,P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of NLR in evaluating BD disease activity was 0.706(95%CI:0.603-0.809).Conclusion NLR is effective in judging the disease activity of BD patients,and can be used as a biological index to evaluate the disease activity of BD.

Objective To explore the application low of stimulation parameters of transcutaneous electrical acupoint stimulation(TEAS)and transcranial direct current stimulation(tDCS)for post-stroke movement disorders based on data mining.Methods The relevant clinical research literature was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed and Web of Science from January 2000 to May 2023.A database was set up after quality assessment.Frequency analysis,association rules and complex network analysis were used to explore the application law of core acupoints and electrical stimulation parameters.Results A total of 79 articles were included and 128 groups of data were contained.For TEAS,the core acupoints included Waiguan(TE5),Shousanli(LI10),Zusanli(ST36),Hegu(LI4),Neiguan(PC6),Yanglingquan(GB34),etc.,while the most commonly used acupoint combinations of upper limb and lower limb were Shousanli(LI10)-Waiguan(TE5)and Yanglingquan(GB34)-Zusanli(ST36).Among the electrical stimulation parameters of TEAS,the frequencies used vary widely,and 100 Hz was most commonly used,while 2 Hz TEAS was also mainly used for stimulating acupoints located on upper limbs in the treatment of flaccid paralysis.The application of other electrical stimulation parameters was relatively consistent.The bidirectional symmetrical square-wave with 200-250 μs pulse-width was used in majority of studies.The stimulus intensity was mostly determined by patient tolerance.For tDCS,stimulation electrodes were often positioned on the projection of the primary M1,and the safe stimulus intensity was mostly set as 1 to 2 mA.Conclusion In the treatment of post-stroke movement disorders,appropriate acupoints and electrical stimulation parameters of TEAS should be determined on the muscle strength and muscle tension of stroke patients at different stages after stroke,particularly the selection of electric stimulating frequency.

Objective:To study the epidemic characteristics of scrub typhus in Yantai City from 2006 to 2022, and provide a scientific basis for prevention and control of scrub typhus in Yantai City.Methods:In the subsystem "Infectious Disease Monitoring System" of the "China Disease Prevention and Control Information System", data on the outbreak of scrub typhus in Yantai City from January 1, 2006 to December 31, 2022 were collected and processed using software such as SPSS 23.0 for descriptive statistics.Results:A total of 599 scrub typhus cases were reported in Yantai City from 2006 to 2022, with an average annual reported incidence of 0.51/100 000. The reported incidence showed an upward trend year by year from 2006 to 2014 (χ 2trend = 144.72, P < 0.001), and reached a peak in 2014 (1.04/100 000). There was another small peak in 2019 (0.91/100 000). The incidence of scrub typhus showed a clear seasonal unimodal distribution, with October being the peak, accounting for 72.62% (435/599). In addition to Changdao County, other 12 cities (districts) reported scrub typhus cases. The top 3 cities with average annual reported incidence were Zhaoyuan City (1.58/100 000), Laizhou City (1.47/100 000) and Laiyang City (0.75/100 000). In all reported cases, the male to female ratio was 1.00∶1.07 (289∶310). The cases were mainly concentrated in the age range of 50 to 79, accounting for 74.46% (446/599). There was a statistically significant difference in the number of patients in different age groups in different years ( H = 38.71, P = 0.001). Farmers accounted for 88.65% (531/599) of the affected population. Conclusions:The incidence of scrub typhus in Yantai City shows an increasing trend and is widely distributed. It is recommended to strengthen the diagnosis, monitoring and infection management of scrub typhus.

Objective:To investigate the safety, feasibility and accuracy of esophageal sponge cytology in esophageal carcinoma screening in high-incidence districts.Methods:Opportunistic screening for esophageal carcinoma was conducted on individuals aged 40-75 years with high-risk factors for esophageal carcinoma and visited out-patient clinic in Lianshui People's Hospital from May 2021 to June 2022. A new esophageal cell collector independently developed in China was used for esophageal sponge cytology sampling followed by cytopathological analysis. Atypical squamous cells or more severe lesions were defined as positive esophageal sponge cytology. Then gastroscopy was performed, and all suspicious areas under the endoscopy were biopsied for histopathological examination. Gastroscopy, biopsy histopathology and esophageal sponge cytology were conducted blindly in pairs. Outcome measures included adverse reactions during sampling, subject tolerability (using a visual simulation score), sampling quality, and diagnostic efficacy of esophageal sponge cytology using gastroscopy plus biopsy histopathology as the gold standard.Results:A total of 1 590 patients completed the screening program. During esophageal sponge cytology sampling, no serious adverse events were observed, and the adverse reactions were mainly manifested as vomiting during sampling [0.31% (5/1 590)] and sore throat after sampling [2.45% (39/1 590)], all of which resolved spontaneously without further medical intervention. The majority of subjects [98.62% (1 568/1 590)] reported good tolerance during the procedure. After sampling, 1 526 (95.97%) subjects had completely expanded sponge material, meeting the standard of good sampling quality. The scanning analysis of the digital pathology system showed that the number of sampled cells in 1 590 subjects ranged (2.01-4.00)×10 6, with a median of 3.48×10 6 cells, which could meet the requirements for interpreting cytological results. Using the positive esophageal sponge cytology for the diagnosis of esophageal carcinoma including high-grade intraepithelial neoplasia, esophageal squamous cell carcinoma and adenocarcinoma of esophagogastric junction, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 98.57% (69/70), 91.51% (1 391/1 520), 34.85% (69/198), 99.93% (1 391/1 392), and 91.82% (1 460/1 590), respectively. Conclusion:Esophageal sponge cytology presents promising diagnostic efficacy for esophageal carcinoma screening, offering a simple, safe, convenient, and effective approach in high-incidence esophageal carcinoma regions.

OBJECTIVE: To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. METHODS: 10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13. RESULTS: The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly. CONCLUSION The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Sex Chromosome Aberrations ; Fetus

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective:To understand the epidemiological characteristics of human brucellosis in Yantai City, Shandong Province, and to provide scientific basis for the formulation and adjustment of brucellosis prevention and control strategy.Methods:The epidemic data, demographic data and case data of human brucellosis in Yantai City in 2019 were collected from the National Health Insurance Disease Control Information System and the epidemiological case survey of brucellosis in Shandong Province. Descriptive epidemiological method was used to analyze the three distribution characteristics, clinical characteristics and infection routes of brucellosis.Results:In 2019, 158 cases of brucellosis were reported in Yantai City, with an incidence rate of 2.22/100 000 and no deaths. The incidence peak was from April to June, accounting for 43.67% (69/158). In addition to Changdao County, 12 other cities and districts had reported brucellosis cases, and Laizhou City had the largest number of reported cases, accounting for 39.87% (63/158). The ratio of men to women was 2.1 ∶ 1.0 (107 ∶ 51). The age of onset was mainly 40 - 69 years (75.95%, 120/158). Farmer was the main occupation, accounting for 83.54% (132/158). The main clinical manifestations were fever (114 cases), muscle and joint pain (107 cases), fatigue (95 cases), hyperhidrosis (85 cases). Patients had a clear history of livestock contact accounted for 58.86% (93/158). The main contact ways were breeding (68 cases) and slaughter (26 cases). Protective measures were taken in 18.28% (17/93) of the patients, and wearing gloves was the most common protective measure, accounting for 76.47% (13/17). The rate of hand washing after contact was 91.40% (85/93), of which 37.65% (32/85) were washed only with water and 62.35% (53/85) were washed with soap. The percentage of changing laundry after contact was 82.80% (77/93).Conclusions:The awareness and ability of personal protection of brucellosis key population in Yantai City are low. Improving the effectiveness of health education and behavior intervention is an important measure for prevention and control of the disease in the future.

Objective:To investigate and analyze a human brucellosis (hereinafter referred to as brucellosis) in Fushan District, Yantai City of Shandong Province, and to provide scientific basis for study the main risk factors and doing a good job in brucellosis prevention and control.Methods:Collect the epidemic data of one human brucellosis in Fushan District, Yantai City in 2017. The information comes from the infectious disease report information management system, the epidemiological case questionnaire of brucellosis in Shandong Province, and the medical records of medical institutions. The epidemic situation, cases and epidemiological investigation results were analyzed retrospectively.Results:Serological tests were carried out among 48 close contacts of the reported case and workers in the same village. Among the 3 positive cases, 2 cases had symptoms and positive bacterial culture results, which were diagnosed as confirmed cases. One patient was asymptomatic and negative bacterial culture, and was diagnosed as recessive infection. All of the three confirmed cases and one recessive infection involved in the epidemic had a history of close contact with infected animals, and without protective measures. The serological examination of 70 key people in the district was carried out and the results were all negative. A total of 166 sheep blood samples were collected, including 21 positive samples.Conclusions:The infectious source of this outbreak is the non-quarantine infected sheep. The main exposure factor is personal unprotected exposure to infected sheep. The key of prevention and control is to strengthen the monitoring and quarantine management of brucellosis among livestock, to improve the personal protection consciousness and ability of key population, and to improve the diagnosis ability of medical institutions in low epidemic areas.

Objective:To investigate the status of Corona Virus Disease 2019 (COVID-19) health literacy and associated factors in Inner Mongolia Autonomous Region.Methods:Based on the multi-stage stratified sampling method, the questionnaire survey of health literacy of COVID-19 were carried out in 55 599 local residents from12 prefecture-level cities of Inner Mongolia Autonomous Region between March 10 and 15, 2020. The questionnaire in details included not only knowledge, attitude and behavior, but also mental health, their scores were calculated using Decimal method. A ≥80% of the correct answer rate of the survey content was regarded as qualified for health literacy. There were 51 722 (93.0%) valid questionnaires, according to the ratio of medical staff to non-medical staff, 32 529 questionnaires were selected for analysis. The health literacy level was defined according to the proportion of qualified people.The credibility and availability of the questionnaires were evaluated by Cronbach′s α coefficient and KMO test. The associated factors were analyzed by Pearson χ 2 test and logistic regression. Results:In Inner Mongolia Autonomous Region, the whole level of health literacy of COVID-19 was 85.7%, and their scores were (26.30±2.48). Knowledge, attitude, and behavioral literacy levels were 61.6%, 95.6%, and 96.8%, respectively. Compared with the population of 15-25 years old, the health literacy level of 46-65 years old was the highest ( OR=2.00, 95% CI: 1.78-2.24). The health literacy level of medical staff group ( OR=2.54, 95% CI: 1.30-4.95) was far higher than the non-medical staff group; the population with college or above education level ( OR=10.22, 95% CI: 9.19-11.36) was significantly higher than the population with education level below college. The degree of anxiety was negatively correlated with education level. Conclusions:The health literacy level of COVID-19 in residents in Inner Mongolia Autonomous Region is relatively high, but the level of knowledge literacy needs to be improved. The main factors affecting the health literacy of COVID-19 among Inner Mongolia residents are age, occupation and education level.

Objective:To analyze the epidemiological characteristics of human brucellosis (referred to as brucellosis) from 2011 to 2018 in Yantai City, and to provide scientific basis for formulating and adjusting brucellosis prevention and control strategies.Methods:Descriptive epidemiological method was used to analyze the monitoring data and epidemiological survey data (time, area, population distribution and treatment behavior) of brucellosis in Yantai from 2011 to 2018.Results:From 2011 to 2018, 795 cases of brucellosis were reported in Yantai, with an annual incidence of 1.42/100 000 and no deaths. Most of the cases were sporadic, accounting for 92.20% (733/795). The incidence peak was from March to August, accounting for 67.80% (539/795). In addition to Changdao County, cases of brucellosis had been reported in 12 counties (cities, districts). The incidence rate of the top three counties (cities, districts) were 5.20/100 000 (369 cases, accounting for 46.42%) in Laizhou City, 2.13/100 000 (97 cases, accounting for 12.20%) in Zhaoyuan City, and 1.77/100 000 (62 cases, accounting for 7.80%) in Penglai City. The male and female sex ratio was 2.82 to 1.00 (587 to 208). The age of onset was mainly 40 - 69 years old, accounting for 79.62% (633/795). Occupation was mainly farmers, accounting for 83.90% (667/795). Cases were mainly found in local medical institutions, accounting for 89.56% (712/795). The average interval between onset and diagnosis was 17 days, the longest was 40 days in 2012, and the shortest was 12 days in 2018.Conclusions:From 2011 to 2018, except Changdao County, 12 counties (cities and districts) in Yantai City had reported brucellosis cases. The incidence peak was in spring and summer, mainly in middle-aged and elderly people, so we should carry out targeted prevention and control strategies for different areas and key populations.