Objective To investigate the epidemiological characteristics of human brucellosis in Tacheng Prefecture, Xinjiang Uygur Autonomous Region, so as to provide insights into formulation of human brucellosis control measures. Methods The epidemiological data of human brucellosis cases in Tacheng Prefecture, Xinjiang Uygur Autonomous Region (excluding the Xinjiang Production and Construction Corps) from 2020 to 2023 were retrieved from the National Notifiable Infectious Diseases Reporting Information System, and population data in Tacheng Prefecture from 2020 to 2023 were collected from 2020 China Population Census by County. A hexagonal grid map was created at a township level using the R 4.5.0 software to examine the spatial distribution and spatial autocorrelation of human brucellosis cases, so as to identify statistically significant spatial clustering pat-terns and clusters. Results A total of 1 798 human brucellosis cases were reported in Tacheng Prefecture, Xinjiang Uygur Autonomous Region from 2020 to 2023, with an average annual incidence rate of 40.54/10⁵. Human brucellosis cases were predominantly detected during the period between March and August (1 291 cases, 71.80% of totally reported cases), and these cases were predominantly male (70.19%), individuals at ages of 30 to 60 years (73.14%), and farmers and herdsmen (86.32%). The highest annual average incidence of human brucellosis was found in Hoboksar Mongol Autonomous County (71.21/10⁵), and a high number of human brucellosis cases was reported in Shawan City and Wusu City (1 160 cases, 64.52% of total cases), which were epidemic-concentrated regions for human brucellosis. Spatial analysis of human brucellosis at a township scale revealed that human brucellosis cases exhibited spatial clustering patterns in Tacheng Prefecture each year from 2020 to 2023 (Moran's I = 0.27 to 0.44, all P values < 0.05). Hotspot townships were primarily concentrated in Shawan City and Wusu City and remained relatively stable, while cold-spot areas gradually expanded. Conclusions Human brucellosis remained highly prevalent in Tacheng Prefecture, Xinjiang Uygur Autonomous Region from 2020 to 2023. Targeted management of sources of infection and high-risk individuals is recommended for human brucellosis control.

OBJECTIVE To investigate the effects of MIR149 rs2292832 and MIR499 rs3746444 gene polymorphisms on the efficacy of tofacitinib combined with iguratimod in the treatment of moderate‑to‑severe rheumatoid arthritis （RA）， to provide genetic reference for individualized treatment of moderate‑to‑severe RA patients.METHODS This was a prospective cohort study， and patients were grouped according to genotyping results. A total of 320 patients with moderate-to-severe RA diagnosed in the department of immunology of our hospital between January 2023 and January 2024 were enrolled. All patients received standardized treatment with tofacitinib （5 mg twice daily） combined with iguratimod （25 mg twice daily） for 24 weeks treatment course. Clinical efficacy outcomes， including American College of Rheumatology （ACR） 20/50/70 responses， disease activity score‑28 based on C‑reactive protein （DAS28-CRP）， erythrocyte sedimentation rate （ESR） and C-reactive protein （CRP）， were compared among patients with different genotypes. Combined-genotype analysis and multivariate Logistic regression analysis were also performed.RESULTS The MIR149 rs2292832 CC-genotype patients exhibited significantly higher ACR20， ACR50 and ACR70 response rates （88.90%， 67.78%， 45.56%） than those carrying CT- and TT-genotypes （ P ＜0.05）. After 24 weeks treatment， the reductions in DAS28‑CRP， ESR and CRP were significantly greater in CC‑genotype patients than in CT‑ and TT‑genotype patients （ P ＜0.05）， and the 24‑week DAS28‑CRP was significantly lower in the CC‑genotype patients than in CT‑ and TT‑genotype patients （ P ＜0.05）. The MIR499 rs3746444 GG-genotype showed significantly higher ACR20， ACR50 and ACR70 response rates （91.46%， 73.17%， 52.44%） than those carrying AG‑ and AA‑genotypes （ P ＜0.05）. After 24 weeks of treatment， the reductions in DAS28‑CRP， ESR and CRP were significantly greater in GG‑genotype patients than in AG- and AA-genotype patients and the 24‑weeks DAS28‑CRP was significantly lower in the GG‑genotype patients than in AG- and AA-genotype patients （ P ＜0.05）. Among the nine combined‑genotyps， the CC+GG genotype yielded the best treatment response. The MIR149 rs2292832 CC and MIR499 rs3746444 GG genotypes were independent predictors of clinical remission （ P ＜0.01）， whereas baseline DAS28‑CRP ≥ 6.5 served as a negative predictor of clinical remission （ P ＜0.05）.CONCLUSIONS Gene polymorphisms of MIR149 rs2292832 and MIR499 rs3746444 significantly influence the therapeutic effect of tofacitinib combined with iguratimod in patients with moderate-to-severe RA. Patients carrying CC and GG genotypes achieve better treatment responses.

Objective:To study the influencing factors of thyroid diseases among residents in a coastal area, Dongtai City, and provide scientific basis for further prevention and control of thyroid diseases.Methods:Thyroid disease patients of Dongtai City in the coastal area diagnosed by Dongtai People's Hospital from January to December 2019 were selected as the survey subjects, and diagnosis of various diseases and their gender and age distribution were analyzed. In the case-control study, confirmed new cases were selected as the case group, and healthy individuals matched 1∶1 by village group, gender, and age as the control group. A questionnaire survey and related examinations such as urinary iodine test and thyroid ultrasound examination were conducted. The survey results were summarized and analyzed (Wilcoxon rank sum test, conditional logistic regression multivariate analysis).Results:(1) A total of 3 508 patients with thyroid diseases were diagnosed, accounting for 319.46/100 000 of the total population, including 2 616 female patients, accounting for 74.57%; 2 824 cases aged 30 to 69 years old, accounting for 80.50%; 1 539 cases of hyperthyroidism, accounting for 43.87%; and 961 cases of hypothyroidism, accounting for 27.39%. (2) A total of 984 cases were surveyed in a 1∶1 paired manner. Multivariate analysis showed that the risk factors for thyroid diseases included monthly average income, family history, related surgeries, personality, working pressure, interpersonal relationships, and urinary iodine grading ( P < 0.05). The risk factors for hyperthyroidism included occupation, family history of hyperthyroidism, personality, family financial pressure, and interpersonal relationships ( P < 0.05), while the risk factor for goiter included urinary iodine grading ( P = 0.008). Conclusions:The occurrence of thyroid diseases in a coastal area, Dongtai City, may be related to family history, gender, age, personality, and working pressure. There is a correlation between goiter and low iodine nutrition level, which further confirms the correctness of the strategy of salt iodization in preventing and treating iodine deficiency disorders in coastal areas.

Objective:To analyze the effect of nucleos(t)ide analog (NAs) antiviral treatment on the clinical features and prognosis of patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC).Methods:A retrospective analysis was performed on the data of 450 HBV-HCC patients first diagnosed and treated in the Third Hospital of Hebei Medical University from January 2015 to January 2021, including 193 patients in the continuous NAs treatment group and 257 patients in the NAs treatment after hepatocellular carcinoma (HCC) group. The baseline data of the two groups were balanced by propensity score matching. The relapse-free survival rate of HCC was estimated by Kaplan-Meier method, and the risk factors for HCC recurrence were analyzed by Cox proportional risk models. Spearman correlation analysis was used to explore the association between clinical features of HCC and hepatitis B virus (HBV) DNA load in patients receiving continuous NAs treatment.Results:Before matching, the proportions of liver cirrhosis, body mass index≥25.0 kg/m 2, single tumor, maximum tumor diameter ≤5 cm, Child-Pugh grade A, China liver cancer staging Ⅰ in the continuous NAs treatment group were 93.8%(181/193), 45.1%(87/193), 70.5%(136/193), 82.4%(159/193), 74.6%(144/193) and 74.6%(144/193), respectively. All of them were higher than those in the NAs treatment after HCC group (87.5%(225/257), 44.0%(113/257), 61.1%(157/257), 55.3%(142/257), 63.8%(164/257) and 56.0%(144/257), respectively). The proportions of drinking history and portal vein tumor thrombi in the continuous NAs treatment group were 12.4%(24/193) and 3.1%(6/193), respectively, which were lower than 33.9%(87/257) and 10.5%(27/257) in the NAs treatment after HCC group.The differences were all statistically significant ( χ2=4.86, 7.58, 4.27, 36.63, 8.15, 21.05, 27.21 and 8.88, respectively, all P<0.05). After matching, the median relapse-free survival time of the patients in the continuous NAs treatment group and the NAs treatment after HCC group were 388 days and 277 days, respectively. The five-year cumulative relapse-free survival rates were 50.0% and 37.5%, respectively, with statistically significant difference ( χ2=5.30, P=0.021). Multivariate analysis showed that no antiviral therapy before diagnosis of HCC, multiple tumors, maximum tumor diameter ≥5 cm and palliative treatment were independent risk factors for HBV-HCC recurrence (hazard ratio ( HR)=1.509, 1.491, 0.446 and 1.472, respectively, all P<0.05). After matching, the maximum tumor diameter ( r=0.175, P=0.042), incidence of portal vein tumor thrombi ( r=0.210, P=0.014) and recurrence of HBV-HCC ( r=0.178, P=0.038) in the continuous NAs treatment group were positively correlated with HBV DNA load. Conclusions:Early initiation of NAs antiviral treatment can improve the tumor characteristics when the disease progresses to HBV-HCC, and improve the relapse-free survival rate of HBV-HCC patients. No antiviral therapy before diagnosis of HCC, multiple tumors, maximum tumor diameter ≥5 cm and palliative treatment are independent risk factors for HBV-HCC recurrence.

COVID-19/virology* ; China/epidemiology* ; Disease Outbreaks ; Genetic Linkage ; Humans ; Phylogeny ; Polymorphism, Single Nucleotide ; SARS-CoV-2/isolation & purification*

OBJECTIVE：To st udy the effects of α7 nicotinic acetylcholine receptor agonists （PNU282987）on improving cardiac remodeling of mice and Janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3）signaling pathway. METHODS：Male Kunming mice were randomly divided into normal control group ，model group ，propranolol group （positive control，i.g. 40 mg/kg）and PNU 282987 low-dose，medium-close and high-dose groups （intraperitoneal injection of 0.5，1.0，3.0 mg/kg），with 10 mice in each group. Except for the normal control group ，mice in the other groups were given isoproterenol （ISO，30 mg/kg） subcutaneously for 7 days to induce the cardiac remodeling model. After 30 minutes of ISO injection ， administration groups were given relevant liquid ，once a day ，for 7 consecutive days. Twelve hours after last administration ，the left ventricular ejection fraction （EF）and left ventricular short axis shortening rate （FS）of mice in each group were measured ，and the whole heart mass index （HMI）was calculated ；the pathological changes of myocardium were observed. The serum contents of lactate dehydrogenase （LDH），creatine kinase （CK），tumor necrosis factor α（TNF-α），interleukin 6（IL-6），the protein expression of intercellular adhesion molecule 1（ICAM-1）and adhesion molecule 1（VCAM-1）were also determined. The ratios of p-JAK2/JAK2，p-STAT3/STAT3 in myocardial tissue were detected. RESULTS ：Compared with normal control group ，EF and FS of model group were significantly reduced ，HMI，the contents of LDH，CK，TNF-α and IL-6，the protein expression of ICAM- 1 and VCAM- 1，the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were increased significantly （P＜0.05 or P＜0.01）； blue collagen deposition in the interstitium of myocardium was obvious，and the degree of fibrosis was severe. Compared with model group ， the EF and FS of the mice in the medium-dose and high-dose groups were increased significantly ， HMI （except for PNU 282987 medium-dose group ），the contents of LDH （except for PNU 282987 medium-dose group ），CK，TNF-α and IL-6，the protein expression of ICAM- 1 and VCAM- 1，the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were decreased significantly （P＜0.05 or P＜ 0.01）；blue collagen deposition in the myocardial interstitium was significantly reduced ，and the degree of myocardial fibrosis was significantly reduced. There was no significant difference in the comparison of the above indicators in PNU 282987 low-dose group （P＞0.05）. CONCLUSIONS ：PNU282987 can improve cardiac remodeling of mice ，the mechanism of which may be associated with inhibiting JAK 2/STAT3 signaling pathway.

Objective:To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT.Methods:Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia.Results:A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95% CI 23.0%-70.6%) , 41.8% (95% CI 17.3%-64.9%) , 8.8% (95% CI 2.9%-26.4%) , and 51.1% (95% CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95% CI 12.7%-73.5%) and 75.0% (95% CI 51.4% -88.8%) ( P=0.017) , respectively. Conclusion:CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

Objective:To investigate the application and clinical outcomes of using 3D computer-assisted printing technique combined with plastic titanium mesh in the reconstruction of maxillary defect.Methods:Clinical data of 14 patients in Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People′s Hospital from January 2016 to June 2018, who were treated for partial or total removal of the maxilla due to benign or malignant tumors and those acquired maxillary defects caused by severe compound trauma were analyzed retrospectively. Twelve males and 2 females were included, with the age ranging from 16 to 51 years old. The sinonasal malignant tumors included squamous carcinoma ( n=2) while benign tumors included hemangioma ( n=1), maxillary fibrous dysplasia ( n=3), maxillary cyst ( n=2) and giant cell tumor of the maxilla ( n=1). Five cases of post-traumatic maxillary defect were also included. According to preoperative thin-layer CT scanning data, computer modeling data was transmitted to a 3D printer to print out the original model and the reconstructed model. Preoperative simulation of tumor removal and maxillary reconstruction was done on the patient′s original model, and the titanium mesh was shaped on the reconstructed model in order to properly reconstruct the area needed to be repaired. The pre-made titanium mesh was implanted into the defect area, the soft tissue flaps were reset, layered stitching and the local pressured bandage were used after surgery. Through postoperative clinical and CT examination, the patient′s maxillofacial shape, nasal function and complications were evaluated. The results were analyzed by descriptive statistical method. Results:Lesions could be completely removed within the predicted range on the preoperative 3D-printed models of all cases. After debridement, titanium mesh could be implanted easily without re-shaping and trimming during surgery as in trauma cases. Titanium mesh could completely cover the missing bone surface closely, with titanium nails fixed smoothly, and the implanted titanium mesh was solid and stable. After the follow-up of 6 to 20 months, all patients were satisfied with the facial symmetry and the function was recovered well.Conclusion:Using 3D computer-assisted printing technique combined with plastic titanium mesh in the reconstruction of maxillary defect can accurately restore the maxillary structure for soft tissue support, and restore the facial shape and function.

Objective To investigate the clinical characteristics and predictors of mortality in patients with candidemia in intensive care unit (ICU). Methods The patients with candidemia admitted to ICU of Peking University People's Hospital from January 2010 to December 2017 were enrolled. The general clinical data, indicators related to Candidia infection and prognosis were collected, and the clinical characteristics, infection characteristics and prognosis of patients with candidiasis were analyzed. Patients were divided into death group and survival group according to hospital survival status. The differences of each index were compared between two groups. The independent risk factors of mortality in patients with candidemia were analyzed by multivariate Logistic regression analysis. Results A total of 95 patients (55 males) with candidemia were included, with an average age of (69.3±16.5) years, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) was 24.7±3.6, sequential organ failure assessment (SOFA) was 6.6±2.7. Candida albicans accounted for the largest proportion of Candida infections (n = 56, 58.9%). Thirty-two (33.7%) patients received inadequate antifungal therapy and 38 (40.0%) patients received inadequate source control. Fifty-five (57.9%) patients were died in hospital. Compared with the survival group, patients in the death group was older (years: 72.5±14.6 vs. 64.9±18.0, P < 0.05), had higher APACHEⅡ and SOFA scores (26.6±2.2 vs. 22.1±3.6, 7.9±2.0 vs. 4.7±2.4, both P ﹤ 0.01), higher rate of glucocorticoid treatment (18.2% vs. 10.0%, P < 0.05), and higher proportion of Candida albicans and Candida glabrata (69.1% vs. 45.0%, 10.9% vs. 7.5%, both P < 0.05), the rate of multi-site Candida infection also significantly increased (47.3% vs. 17.5%, P < 0.05). Intra-abdominal infection was the primary infection site and more common in death group (49.1% vs. 35.0%, P < 0.05). The rates of sepsis (87.3% vs. 62.5%), inadequate antifungal therapy (49.1% vs. 10.0%), inadequate source control (60.0% vs. 12.5%) in death group were all higher than those in survival group (all P < 0.01). It was shown by multivariate Logistic regression analysis that APACHE Ⅱ[odds ratio (OR) = 1.605, P = 0.002, β = 0.473], SOFA (OR = 1.501, P = 0.029, β = 0.406), inadequate antifungal therapy (OR = 12.084, P = 0.006, β = 2.492) and inadequate source control (OR = 7.332, P = 0.024, β = 1.992) were independent risk factors for mortality in ICU patients with candidemia. Conclusions Candidemia patients were severe and had poor prognosis. APACHE Ⅱ, SOFA, inadequate antifungal therapy and inadequate source control were independent risk factors of mortality.

In order to solve the problems that the injury, hemorrhage, infection and edema of the brain tissue caused by brain electrodes implantation for aquatic animal robots, a light stimulation device and an optical control experiment method for carp robots are proposed in this paper. According to the shape of the carp skull, the device is a structure of Chinese character " cut by a printed circuit board which can provide three groups of A, B and C bridge platforms for the light stimulation source. The two ends of a bridge in every group are welded with a jumper board, and the light emitting diodes (LED) are inserted into the jumper boards as the light stimulation source, and all negative poles of the jumper boards are connected to the console by the wire. A LED light can be replaced by another LED light according to the need of the wavelength of the LED light, and various combinations of the light stimulation modes can be also selected. This device was mounted on the carp robot's head, the carp robot was placed in a water maze, and the optical control experiment method was observed to control the forward movement and steering movement of the carp robots ( = 10) under the dark light condition. The results showed that the success rates of the three groups of red light control experiments were 53%-87%, and the success rates of the three groups of blue light control experiments were 50%-80%. This study shows that the apparatus and the method are feasible.