Genetically Supported Drug Targets and Dental Traits: A Mendelian Randomization Study.

Current interventions for oral/dental diseases heavily rely on operative/surgical procedures, while the discovery of novel drug targets may enable access to noninvasive pharmacotherapy. Therefore, this study aims to leverage large-scale data and Mendelian randomization (MR) techniques, utilizing genetic variants as instruments, to identify potential therapeutic targets for oral and dental diseases supported by genetic evidence. By intersecting 4,302 druggable genes with expression quantitative trait loci from 31,684 blood samples, we identified 2,580 druggable targets as exposures. Single nucleotide polymorphisms associated with dental disease/symptom traits were collected from FinnGen R9, the Gene-Lifestyle Interactions in Dental Endpoints consortium, and the UK Biobank to serve as outcomes for both discovery and replication purposes. Through MR analysis, we identified 43 druggable targets for various dental disease/symptom traits. To evaluate the viability of these targets, we replicated the analysis using circulating protein quantitative trait loci as exposures. Additionally, we conducted sensitivity, colocalization, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotation, protein-protein interaction analyses, and validated dental trait-associated druggable gene expression in animal models. Among these targets, IL12RB1 (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.01-1.01) and TNF (OR, 0.98; 95% CI, 0.97-0.99) exhibited therapeutic promise for oral ulcers, whereas CXCL10 (OR, 0.84; 95% CI, 0.76-0.91) was for periodontitis. Through a rigorous quality control and validation pipeline, our study yields compelling evidence for these druggable targets, which may enhance the clinical prognosis by developing novel drugs or repurposing existing ones.

CriteriaMapper: establishing the automatic identification of clinical trial cohorts from electronic health records by matching normalized eligibility criteria and patient clinical characteristics.

The use of electronic health records (EHRs) holds the potential to enhance clinical trial activities. However, the identification of eligible patients within EHRs presents considerable challenges. We aimed to develop a CriteriaMapper system for phenotyping eligibility criteria, enabling the identification of patients from EHRs with clinical characteristics that match those criteria. We utilized clinical trial eligibility criteria and patient EHRs from the Mount Sinai Database. The CriteriaMapper system was developed to normalize the criteria using national standard terminologies and in-house databases, facilitating computability and queryability to bridge clinical trial criteria and EHRs. The system employed rule-based pattern recognition and manual annotation. Our system normalized 367 out of 640 unique eligibility criteria attributes, covering various medical conditions including non-small cell lung cancer, small cell lung cancer, prostate cancer, breast cancer, multiple myeloma, ulcerative colitis, Crohn's disease, non-alcoholic steatohepatitis, and sickle cell anemia. About 174 criteria were encoded with standard terminologies and 193 were normalized using the in-house reference tables. The agreement between automated and manual normalization was high (Cohen's Kappa = 0.82), and patient matching demonstrated a 0.94 F1 score. Our system has proven effective on EHRs from multiple institutions, showing broad applicability and promising improved clinical trial processes, leading to better patient selection, and enhanced clinical research outcomes.

[Epidemiological characteristics of imported malaria after malaria elimination in Shanxi Province, 2019-2023].

Objective: To analyze the epidemiological characteristics of imported malaria cases from 2019 to 2023 after the elimination of malaria in Shanxi Province, and provide reference for formulating scientific and effective malaria prevention and control strategies in Shanxi Province. Methods: The data of imported malaria cases were collected China Information System for Disease Control and Prevention and National Parasitic Disease Control Information Management System in Shanxi Province, from 2019-2023. Descriptive epidemiological method and SPSS 26.0 statistical software were used for descriptive epidemiological statistical analysis. Results: A total of 51 malaria cases were reported in Shanxi Province in 2019-2023, all imported from abroad. Among them, there were 38 cases of falciparum malaria (74.51%), 6 cases of plasmodium ovale (11.77%), 5 cases of plasmodium vivax (9.80%), 1 case of plasmodium triticum malaria (1.96%), and 1 case of mixed infections (1.96%), with nodeaths; cases were predominantly males (94.12%, 48/51) and workers who went abroad for work (84.31%,43/51); the median age of onset was 37 years old; and there were imported cases every month, with no obvious peak of incidence; Taiyuan City reported the most cases, accounting for 72.55% (37/51) of the total number of cases,the source of infection of cases was mainly from Africa (96.08%), with the Democratic Republic of the Congo (16 cases), Nigeria (6 cases), Equatorial Guinea (5 cases), Mozambique (3 cases), and Republic of the Congo (3 cases) in that order; the median time between the onset of disease and first diagnosis, and the median time between first diagnosis and confirmation, were two times longer than that of first diagnosis, and the median time between first diagnosis and confirmation was two times longer than that of first diagnosis. The M(Q1, Q3) intervals from onset to first diagnosis and from first diagnosis to confirmed diagnosis were 2(0,4) days and 1(0,3) days, respectively, with statistically significant differences between different years from onset to first diagnosis (H=17.41, P=0.048), and from first diagnosis to confirmed diagnosis (H=20.82, P=0.010). A total of 101 146 blood tests for febrile patients were conducted in the province during the five years, with the minimum number of blood tests in 2020 (19 867 person-times) and the maximum number of blood tests in 2023 (20 778 person-times). Conclusions: After the elimination of malaria in Shanxi Province from 2019 to 2023, all malaria cases were imported from abroad, and it is still necessary to strengthen the surveillance of people traveling to and from malaria-endemic areas, implement the combination of medical treatment and prevention, and jointly prevent and control the occurrence of imported malaria.

[Treatment of refractory diffuse large B-cell lymphoma involving the central nervous system with polatuzumab vedotin-based regimen: a case report and literature review].

Polatuzumab vedotin (Pola) is a novel antibody-drug conjugate targeting CD79b, which has been shown to be effective in treating newly diagnosed and relapsed/refractory diffuse large B cell lymphoma (DLBCL) during clinical trials. This study aims to conduct a retrospective analysis of the clinical characteristics, diagnosis, and treatment of a patient with refractory secondary central nervous system lymphoma at Beijing Hospital, alongside a review of relevant literature. This study included a 79-year-old female patient who was diagnosed with DLBCL affecting the ilium, sacrum, spinal cord, and nerve roots and had an IPI score of 5 and a high-risk score according to MSKCC. She showed a geriatric comprehensive assessment (IACA) score of 2, which was categorized under the unfit group. Her initial treatment comprised chemo-free therapy and radiotherapy, followed by progression. In the second-line treatment, a Pola-based regimen was applied, and the patient achieved a complete response, suggesting that this regimen may be a therapeutic option for patients with DLBCL involving the central nervous system.

[Bidirectional causal relationship between glucose-lipid metabolism, obesity indicators, and myocardial infarction: a bidirectional Mendelian randomization analysis study].

Objective: To explore the causal association of glucose-lipid metabolism and obesity indicators with myocardial infarction by a two-sample Mendelian randomization analysis. Methods: Single nucleotide polymorphisms (SNPs) related to phenotypes were obtained from genome-wide association study databases. The body mass index (BMI) and glycated hemoglobin dataset includes 99 998 samples and 8 126 035 SNPs; the waist-to-hip ratio dataset includes 224 459 samples and 2 562 516 SNPs; the waist circumference and hip circumference dataset includes 462 166 samples and 9 851 867 SNPs; the fasting glucose dataset includes approximately 12 million SNPs; the low-density lipoprotein cholesterol (LDL-C) dataset includes 201 678 samples and 12 321 875 SNPs; the high-density lipoprotein cholesterol (HDL-C), and triglycerides dataset includes 156 109 samples and 15 784 414 SNPs; and the body fat percentage, whole-body fat mass, trunk fat percentage, and trunk fat mass dataset includes 454 588 samples and 9 851 867 SNPs. This study primarily used inverse-variance weighted method to analyze the associations between various exposure factors and outcomes. Heterogeneity among SNPs was assessed using Cochran's Q test, and horizontal pleiotropy of SNPs was examined using the MR-Egger method. Additionally, a multivariable MR approach was used to adjust for BMI, further validating associations between exposure factors and the risk of myocardial infarction. Results: Higher BMI (OR=1.070, 95%CI: 1.041-1.100), waist-to-hip ratio (OR=1.366, 95%CI: 1.113-1.677), LDL-C (OR=1.638, 95%CI: 1.488-1.803), triglycerides (OR=1.445, 95%CI: 1.300-1.606), waist circumference (OR=1.841, 95%CI: 1.650-2.055), hip circumference (OR=1.247, 95%CI: 1.132-1.372), body fat percentage (OR=1.795, 95%CI: 1.568-2.055), whole-body fat mass (OR=1.519, 95%CI: 1.381-1.670), trunk fat percentage (OR=1.538, 95%CI: 1.374-1.723), and trunk fat mass (OR=1.421, 95%CI: 1.294-1.561), as well as lower HDL-C (OR=0.799, 95%CI: 0.729-0.875), have causal effects on myocardial infarction (all P<0.05). After adjusting for BMI, hip circumference, trunk fat percentage, and trunk fat mass were no longer associated with myocardial infarction. However, waist-to-hip ratio (OR=1.457, 95%CI: 1.132-1.877), fasting glucose (OR=1.191, 95%CI: 1.024-1.383), glycated hemoglobin (OR=1.129, 95%CI: 1.034-1.233), LDL-C (OR=1.592, 95%CI: 1.314-1.929), triglycerides (OR=1.410, 95%CI: 1.279-1.553), waist circumference (OR=1.922, 95%CI: 1.448-2.551), body fat percentage (OR=1.421, 95%CI: 1.072-1.884), and whole-body fat mass (OR=1.295, 95%CI: 1.031-1.626) remained positively associated with myocardial infarction, while HDL-C (OR=0.809, 95%CI: 0.729-0.897) remained negatively associated. Conclusions: Abdominal obesity and dysregulation of glucose-lipid metabolism are risk factors for myocardial infarction. Screening for glucose-lipid metabolism (fasting glucose, HDL-C, LDL-C, triglycerides) and obesity-related indicators (waist circumference, waist-to-hip ratio, body fat percentage, and whole-body fat mass) is of great importance for the primary prevention of myocardial infarction.

[Clinical features of KCNB1 gene variation related developmental and epileptic encephalopathy].

Objective: To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children. Methods: A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children's Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children's Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed. Results: All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control. Conclusions: KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.

[Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma].

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Structural changes of potato starch and activity inhibition of starch digestive enzymes by anthocyanin from lingonberry (Vaccinium uliginosum L.) retarded starch digestibility.

The effects of anthocyanins on in vitro and in vivo digestibility of potato starch were evaluated in this study. Then the influence of anthocyanins on physicochemical property of potato starch and the activity of starch digestive enzymes (α-amylase and α-glucosidase) were also investigated to understand the mechanism of anthocyanins on starch digestibility. Results have shown that dietary anthocyanins could effectively inhibit the biological activities of α-amylase and α-glucosidase to delay the peak of postprandial blood glucose. Characterization of physicochemical properties of potato starch indicates a structural change due to the presence of anthocyanins, hindering its access to starch digestive enzymes. Among all anthocyanins, lingonberry anthocyanin significantly promoted the retrogradation of potato starch (7.153 % to 25.913 %) and exert promising inhibition on α-amylase and α-glucosidase. Lingonberry anthocyanins mainly interacted with potato starch through hydrogen bonds, which reduce the amount of amylose molecules leached from potato starch and loosen the three-dimensional (3D) network structure of starch gel. This study could provide theoretical evidence for utilization of anthocyanins in diabetic-management function food.

[Clinical application of parasacral artery perforator flap in the treatment of Pilonidal Sinus Diseases].

Objective: To investigate clinical efficacy of parasacral perforator flap (PPF) on postoperative wound healing in pilonidal sinus diseases (PSDs). Methods: The surgery steps were as follows: (1) To preoperatively detect parasacral perforator arteries with the handhold Doppler probe and mark them; (2) To remove the infected and necrotic tissues of PSDs completely; (3) To design the PPF according to the wound size and the parasacral perforator arteries' localization; (4) To harvest the flap from the gluteus maximus muscle surface and transfer it to the wound without tension. Several data were documented, including surgical duration, flap length, flap width, drainage tube placement duration, hospital stay, duration from operation to stitch removal, postsurgical complications and recurrence. Results: There were six patients with PSDs whose postoperative wound healing was repaired by PPF, admitted in our department from March 2021 to March 2023. Of them, five were male and one was female. Their median age was 24 (range: 18-33) years old. Their median surgical duration was 165 (range: 134-207) minutes, median length of PPF was 8 (range: 7-11) cm, median width of PPF was 3 (range: 3-4) cm, mean duration of drainage tube placement was 8 (range: 4-17) days, mean hospital stay was 13 (range: 6-23) days, mean duration from operation to stitch removal was 14 (range: 14-17) days, median follow-up time was 6-16 months. Incisions of all six cases achieved first-intention healing without early- or late-stage complications. No recurrence occurred during follow-up. All patients involved were satisfied with their clinical efficacy. Conclusion: The utility of PPF in postoperative wound healing of PPDs was effective, safe and reliable.

[SUV3 knockdown inhibits proliferation, migration, and invasion of hepatocellular carcinoma cells and induces PD-L1 expression].

Objective: To study the SUV3 gene role during the process of occurrence and advancement of hepatocellular carcinom. Methods: The The differences in SUV3 expression between hepatocellular carcinoma tissues and normal liver tissues were compared by analyzing transcriptome sequencing data from TCGA and GTEx databases. SUV3 knockdown in different hepatocellular carcinoma cells was performed using RNA interference technology. Overexpression vectors were constructed to overexpress SUV3 in different hepatocellular carcinoma cells. The SUV3 regulatory effect was studied on proliferation, migration, and invasion of hepatocellular carcinoma cells. A subcellular fraction isolation approach was used to investigate whether SUV3 knockdown resulted in the release of mitochondrial DNA into the cytoplasm. Quantitative reverse transcription PCR was applied to investigate whether SUV3 knockdown affected PD-L1 expression. The two groups were compared using a two-tailed t-test. Results: The TCGA database analysis revealed that SUV3 expression was higher in hepatocellular carcinoma tissues than in normal liver tissues, and the prognosis of patients with high SUV3 expression in hepatocellular carcinoma tissues was poor. The quantitative RT-PCR results showed that SUV3 expression was higher in hepatocellular carcinoma tissues than that in paracancerous liver tissue. The MTS assay showed that with SUV3 knockdown, the proliferation rate was significantly lower in hepatocellular carcinoma cells than that of the control hepatocellular carcinoma cells (P<0.01). The proliferation rate was significantly higher in SUV3-overexpressed hepatocellular carcinoma cells than that of control hepatocellular carcinoma cells (P<0.01). Cell scratch assay and cell migration and invasion assay showed that SUV3 knockdown inhibited the migration and invasion of hepatocellular carcinoma cells (P<0.01), while SUV3 overexpression promoted the migration and invasion of hepatocellular carcinoma cells (P<0.05). SUV3 Knockdown led to a decrease in the overall level of mtDNA (P<0.01) in accompanied by an increase in mtDNA level in the cytoplasm (P<0.01), indicating that SUV3 knockdown led to mitochondrial DNA leakage into the cytoplasm. SUV3 knockdown resulted in elevated PD-L1 expression (P<0.001), and overexpression of TREX1 in SUV3 knockdown cells decreased mtDNA levels in the cytoplasm and inhibited SUV3 knockdown, resulting in elevated PD-L1 expression, indicating that SUV3 knockdown induced PD-L1 expression by increasing cytoplasmic DNA levels. Conclusions: The SUV3 gene may play an oncogenic function in hepatocellular carcinoma cells.

[Current status of interventional bronchoscopy in chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases with the highest disease burden in China. In the past, the treatment of COPD was mainly based on drugs. In recent years, interventional bronchoscopy has been tried for the treatment of COPD and some progress has been made. This paper reviewed the clinical application of interventional bronchoscopy for the treatment of COPD to provide information for clinicians.

[The efficacy and safety of ibrutinib in the treatment of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia].

Objective: To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenström macroglobulinemia (WM) . Methods: Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety. Results: A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion: Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

[Changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis].

Objective: To observe the changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis at different time points. Methods: In June 2021, 96 healthy male SD rats with SPF grade were divided into 1, 3, and 6-month control group and dust staining group (coal dust group, coal silica dust group, quartz group) according to random number table method, with 8 rats in each group. After one week of adaptive feeding, a one-time non-exposed tracheal perfusion method (1 ml/ piece) was used. The dust dyeing group was given 50 g/L coal dust, coal silica mixed dust and quartz dust suspension, respectively, and the control group was given 0.9% normal saline solution. At 1, 3 and 6 months after perfusion, lung function was detected by animal lung function apparatus, then all lung tissues and alveolar lavage fluid were killed, and lung histopathological morphological changes were observed by HE staining, and the contents of interleukin (IL-1ß), IL-18, IL-4 and IL-10 in alveolar lavage fluid were detected by ELISA. One-way analysis of variance was used to compare groups. Two factors (inter-group treatment factor (4 levels) and observation time factor (3 levels) ) were used in the analysis of the effects of inter-group treatment and treatment time on related indicators. Results: HE staining results showed that coal spot appeared in the lung tissue of coal dust group, coal spot and coal silicon nodule appeared in the lung tissue of coal dust group, and silicon nodule appeared in the lung tissue of quartz group. Compared with the control group, the forced vital capacity (FVC) and forced expiratory volume at 0.2 second (FEV(0.2)) of rats in the dust staining group had interaction between the treatment and treatment time (P<0.05). With the increase of dust dyeing time, FVC and FEV(0.2) decreased significantly at 3-6 months of dust dyeing, and the maximum gas volume per minute (MVV) decreased significantly at 1-3 months of dust dyeing (P<0.05). The lowest lung function index was in quartz group, followed by coal-silica group and coal-dust group. There were statistically significant differences in the main effect and interaction effect of the pro-inflammatory factor IL-18 among all groups in treatment and treatment time (IL-18: F=70.79, 45.97, 5.90, P<0.001), and interaction existed. The highest content of inflammatory factors in alveolar lavage fluid of all dust groups was quartz group, followed by coal silica group and coal dust group. There were significant differences in the main effect and interaction effect of anti-inflammatory factors between groups and treatment time (IL-4: F=41.55, 33.01, 5.23, P<0.001, <0.001, <0.001; IL-10: F=7.46, 20.80, 2.91, P=0.002, <0.001, 0.024), and there was interaction. The highest content of anti-inflammatory factor was in quartz group, followed by coal silica group and coal dust group. Conclusion: Lung function decreased and levels of inflammatory fators increased in rat models of coal workers' pneumoconiosis, with the quartz group being the most severely damaged. Lung function is mainly impaired in thrid-six months, and the content of inflammatory factors begins to change in first-thrid months. MVV are the earliest and most obvious in lung function. IL-18 is suitable for monitoring changes in the pro-inflammatory response of coal workers' pneumoconiosis, and IL-10 is suitable for monitoring changes in anti-inflammatory response.

[Learning curve for a five-step procedure, transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction].

Objective: To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction. Methods: In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M(Q1, Q3) and the Mann-Whitney U test was used for inter group comparison. Results: The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x3-4.4757x2+164.97x-264.4 (P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor (P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups (P=0.238). Conclusion: Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

Women's healthcare autonomy and the utilization of maternal healthcare services in Afghanistan.

OBJECTIVES: The objective of this study was to investigate the relationship between women's healthcare autonomy and the utilization of maternal healthcare services (MHS), including antenatal care services, the services of health professionals at the birth of a child, and facility-based delivery. STUDY DESIGN: This was a cross-sectional study. METHODS: This study utilized data from the 2015 Afghanistan Demographic and Health Survey (AFDHS 2015), which included women aged 15-49 years who had given live birth within the five years before the survey. Multilevel logistic regression was used to estimate the adjusted odd ratios (AOR) for each outcome variable. RESULTS: Among respondents, 16.49% made at least four ANC visits, 52.57% of childbirth were assisted by a skilled birth attendant (SBA), and 45.60% of children were born in health facilities. Women with high healthcare autonomy, compared to medium and low, were more likely to use ANC (AOR 1.45; 95% CI = 1.26-1.67), SBA (AOR 1.15; 95% CI 1.02-1.29), and FBD (AOR 1.12; 95% CI 1.04-1.20). The association between women's healthcare autonomy and the use of maternal healthcare services (MHS) was positively and significantly moderated by household wealth and women's access to media. CONCLUSION: Women's higher healthcare autonomy was significantly and positively associated with MHS in Afghanistan. Policy and programs that encourage women's empowerment and awareness of the importance of MHS utilization should be initiated.

[Effect of deletion of protein 4.1R on proliferation, apoptosis and glycolysis of hepatocyte HL-7702 cells].

OBJECTIVE: To explore the effects of deletion of protein 4.1R on hepatocyte proliferation, apoptosis, and glycolysis and the molecular mechanisms. METHODS: A 4.1R-/- HL-7702 cell line was constructed using CRISPR/Cas9 technique, and with 4.1R+/+HL-7702 cells as the control, its proliferative capacity and cell apoptosis were assessed using CCK-8 assay, EdU-488 staining, flow cytometry and Annexin V-FITC/PI staining at 24, 48, 72 h of cell culture. The changes in glucose uptake, lactate secretion, ATP production and pH value of the culture supernatant of 4.1R-/- HL-7702 cells were determined. The mRNA expressions of the key regulatory enzymes HK2, PFKL, PKM2 and LDHA in glycolysis were detected with qRT-PCR, and the protein expressions of AMPK, p-AMPK, Raptor and p-Raptor were determined using Western blotting. RESULTS: Western blotting and sequencing analysis both confirmed the successful construction of 4.1R-/- HL-7702 cell line. Compared with the wild-type cells, 4.1R-/- HL-7702 cells exhibited a lowered proliferative activity with increased cell apoptosis. The deletion of protein 4.1R also resulted in significantly decreased glucose uptake, lactate secretion and ATP production of the cells and increased pH value of the cell culture supernatant. qRT-PCR showed significantly decreased mRNA expressions of the key regulatory enzymes in glycolysis in 4.1R-/- HL-7702 cells. Compared with those in HL-7702 cells, the expression levels of AMPK and Raptor proteins were decreased while the expression levels of p-AMPK and p-Raptor proteins increased significantly in 4.1R-/- HL-7702 cells. CONCLUSION: Deletion of protein 4.1R in HL-7702 cells results in reduced proliferative capacity, increased apoptosis and suppression of glycolysis, and this regulatory mechanism is closely related with the activation of the downstream AMPK-mTORC1 signaling pathway.

[Prevalence and epidemiological characteristics of major chronic diseases in people living with HIV in Taizhou, Zhejiang Province, 1998-2022].

Objective: To understand the prevalence of major chronic diseases of diabetes, cardiovascular disease and malignant tumor in people living with HIV in Taizhou. Methods: The data were collected from China Information System for Disease Control and Prevention and Taizhou Chronic Disease Information Management System. A total of 5 126 people living HIV under follow-up in Taizhou from 1998 to 2022 were included in the analysis. Software SAS 9.4 was used for χ2 test, trend analysis and logistic regression analysis. Results: In the 5 126 people living with HIV, the reported prevalence rates of diabetes,cardiovascular disease and malignant tumor were 10.28% (527/5 126),3.98% (204/5 126) and 6.01% (308/5 126), respectively. 37.00% (195/527) and 48.58% (256/527), 40.20% (82/204) and 48.53% (99/204), 37.66% (116/308) and 48.38% (149/308) were diagnosed as diabetes, cardiovascular disease and malignant tumor before and after confirmation of HIV infection. From 2013 to 2022, the proportion of HIV infected people diagnosed with diabetes, cardiovascular disease and malignant tumor after confirmation increased (trend χ2=79.98,P<0.001; trend χ2=17.44,P<0.001; trend χ2=32.06,P<0.001). Based on the analysis on the factors for complicated chronic diseases in people living with HIV, it was found that women under 60 years old (aOR=0.66, 95%CI: 0.50-0.86) and those with access to antiviral treatment for >5 years before 2016 (aOR=0.54,95%CI:0.37-0.78) were less likely to develop complicated chronic diseases, and those under 60 years old with initial CD4+T lymphocytes counts <200 cells/µl (aOR=1.32, 95%CI: 1.02-1.70), those aged 40-49 and 50-59 years (aOR=2.88, 95%CI:2.20-3.79; aOR=5.43, 95%CI: 4.10-7.21) as well as those without a record of treatment medication use after 2016 (aOR=1.95,95%CI:1.20-3.16) were more likely to develop complicated chronic diseases. The probability of developing complicated chronic diseases might increase with age in people living with HIV. Conclusions: From 1998 to 2022, there was a certain proportion of complicated chronic diseases among HIV infected individuals in Taizhou, and the proportion of diagnosed cases increased after HIV infection was confirmed. It is necessary to conduct early chronic disease screening, behavior intervention and standardized management in people living with HIV.

[Genotype and phenotype of WWOX gene related developmental and epileptic encephalopathy].

Objective: To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE). Methods: Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children's Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children's characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed. Results: Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.