[2, 6-dimethoxy-1, 4-benzoquinone alleviates septic shock in mice by inhibiting NLRP3 inflammasome activation].

OBJECTIVE: To investigate the mechanism of 2, 6-dimethoxy-1, 4-benzoquinone (DMQ), an active ingredients in fermented wheat germ extract, for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice. METHODS: Cultured murine bone marrow-derived macrophages (BMDM) stimulated with lipopolysaccharide (LPS) were treated with DMQ, followed by treatment with Nigericin, ATP, and MSU for activating the canonical NLRP3 inflammasome; the noncanonical NLRP3 inflammasome was activated by intracellular transfection of LPS, and AIM2 inflammasome was activated using Poly A: T.In human monocytic THP-1 cells, the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ, the levels of IL-1ß and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA, and the survival time of the mice within 36 h was observed. RESULTS: Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM, but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock, DMQ treatment significantly reduced the levels of IL-1ß in the serum and peritoneal fluid and obviously prolonged survival time of the mice. CONCLUSION: DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPSinduced septic shock in mice.

[Effect of zirconia personalized gingival penetration on peri-implant soft and hard tissue of thin gingival biotypes in the anterior region: a retrospective study].

Objective: To investigate the effect of zirconia personalized gingival structure on peri-implant soft and hard tissue stability after single-tooth implant restorations in patients with thin gingival biotypes in the anterior region, with a view to provide a clinical guideline. Methods: This retrospective study included 20 patients with thin gingival biotype and implant restorations in the anterior region. These patients included 9 males and 11 females, and the age was (35.2± 10.3) years. The patients were from the Department of Periodontal Implantology, Stomatology Hospital, Southern Medical University from January 2018 to December 2022. Computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate a titanium base zirconia personalized gingival structure to maintain the soft-tissue perforated gingival contour of the anterior esthetic zone. This structure consists of two modalities: titanium base + zirconia outer crown or titanium base personalized zirconia abutment + zirconia outer crown. Clinical outcomes were recorded immediately and after delivery of the final restorations. Implant retention was recorded, esthetic scoring was performed using the pink esthetic index, the amount of bone resorption at the implant margins was measured based on digitized apical radiographs, and periodontal health was evaluated using the modified plaque index and the modified bleeding index. Results: The survival rate of the 20 implants was 100% after 3 years of wearing the final restorations, with a pink aesthetic score of 9.3±0.9. Bone resorption at the proximal and distal mesial margins of the implants was 0.09 (-0.21, 0.20) mm, 0.17 (-0.12, 0.27) mm after 3 years, respectively, and the difference was not statistically significant when compared to bone resorption immediately after placement of the final restoration [0(0, 0) mm] (Z=-1.03, P=0.394; Z=-2.05, P=0.065). Conclusions: Zirconia personalized gingival structure maintains the stability of peri-implant hard and soft tissues of thin gingival biotypes in the anterior region.

[Genotype-phenotype relationship and genetics study of 115 cases with Wilson's disease].

Objective: To explore the genotype-phenotype relationship of Wilson's disease (WD) and further study the mutation spectrum in the ATP7B gene. Methods: The clinical data and genetic test results of 115 cases with WD diagnosed in the First Affiliated Hospital of Zhengzhou University from 2015 to 2022 were retrospectively analyzed. The rank sum test was used for quantitative data comparison, and χ(2) test was used for count data comparison. Multivariate logistic regression was used to analyze the relationship between patients' genotype and phenotype. Results: The onset of liver manifestations (hepatic type) accounted for 60.9%, neurological symptoms (cerebral type) for 13.0%, and mixed hepato-cerebral symptoms for 26.1%. Presymptomatic individuals (hepatic types) accounted for 62.9%. Next-generation sequencing- diagnosed WD cases accounted for 87.8%. Combined multiplex ligation-dependent probe amplification assay-diagnosed WD cases accounted for 89.6%. A single case with a detected pathogenic locus accounted for 10.4%. The diagnostic rate of WD by genetic testing combined with clinical data was 100%. A total of 76 ATP7B mutations were detected, and the top three mutation frequencies were c.2333G>T (p.Arg778Leu) (30.7%), c.2975C>T (p.Pro992Leu) (7.3%), and c.2621C>T (p.Ala874Val) (6.4%). The mutations were mainly distributed in exons 8, 11-13, and 15-18, accounting for more than 90% of the total mutations. Eight new mutations were found, including c.3724G>A (p.Glu1242Lys), c.3703G>C (p.Gly1235Arg), c.3593T>C (p.Val1198Ala), c.2494A>C (p.Lys832Gln), c.1517T>A (p.Ile506Lys), c.484G>T (p.Glu162Ter), c.1870-49A>G, and the missing of exons 10-21. Liver histopathology showed cellular edema, degeneration, inflammation, and necrosis, as well as a 42.8% copper staining positive rate. Genotype-phenotype analysis showed that the p.Arg778Leu mutation had higher alanine aminotransferase (ALT) levels than those carrying other mutations (P=0.024), while the homozygous mutation of p.Arg778Leu was associated with cerebral-type patients (P=0.027). Conclusion: Genetic testing plays an important role in the diagnosis of WD. p.Arg778Leu is the first high-frequency mutation in the Chinese population, and patients carrying it have higher ALT levels. The p.Arg778Leu homozygous mutation is prone to causing cerebral-type WD. This study expands the ATP7B gene mutation spectrum.

Risk factors for infection in patients undergoing shoulder arthroscopy: a systematic review and meta-analysis.

We conducted a meta-analysis to determine the risk of infection following shoulder arthroscopy and to identify risk factors for infection. We systematically searched the PubMed/Medline, Embase and Cochrane Library databases, as well as the reference lists of previous systematic reviews and meta-analyses; manual searches were also performed. A random-effects model was employed to estimate pooled odds ratios (ORs), based on sample size, the P-value of Egger's test and heterogeneity among studies. Of the 29,342 articles screened, 16 retrospective studies comprising 74,759 patients were included. High-quality evidence showed that patients with diabetes (OR, 1.30; 95% confidence interval (CI), 1.20-1.41) or hypertension (OR, 1.26; 95% CI, 1.10-1.44) had a higher risk of infection, while moderate quality evidence showed that patients with obesity (body mass index ≥30 kg/m2) (OR, 1.42; 95% CI, 1.28-1.57), those who were male (OR, 1.65; 95% CI, 1.12-2.44), those who had an American Society of Anesthesiologists (ASA) class ≥3 (OR, 2.02; 95% CI, 1.02-3.99) and those who had a history of smoking (OR, 2.44; 95% CI, 1.39-4.28) had a higher risk of infection. The meta-analysis revealed that there was no association between age, time of surgery, or alcohol consumption and infection. This meta-analysis identified six significant risk factors for infection following shoulder arthroscopy including diabetes, obesity, hypertension, male sex, ASA class, history of smoking. These patient-related risk factors may help identify postoperative patients at higher risk for infection following shoulder arthroscopy.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

Investigating the Impact of Tea Consumption on Cognitive Function and Exploring Tea-Genetic Interactions in Older Adults Aged 65-105 Years: Findings from the 2002-2018 CLHLS Data.

BACKGROUND: As the global population ages, cognitive impairment (CI) becomes more prevalent. Tea has been one of the most popular drinks in the world. Several studies have demonstrated that tea consumption has an impact on cognitive function. OBJECTIVE: This study aims to examine the association between tea consumption and cognitive function and explore the potential effect of genetics on the relationship between tea consumption and CI risk in older adults. DESIGN: This is a prospective longitudinal study using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). SETTING: Six waves of data from CLHLS containing 76,270 subjects were analyzed. Generalized estimation equations (GEE) with a logit link function were adopted to estimate the effect of tea consumption on CI risk from a cross-sectional and longitudinal perspective. PARTICIPANTS: A population-based cohort of adults aged 65-105 years. MEASUREMENTS: The frequency and type of tea consumption were obtained by questionnaires. CI was measured based on MMSE. Polygenic risk was measured using the polygenic score approach described by the International Schizophrenia. RESULTS: The results showed that drinking green tea had a better protective effect on cognitive function than other types of tea, the incidence of CI gradually decreased with the increase of tea consumption frequency, and men were more likely to benefit from tea consumption. Additionally, we also found a significant interaction between tea consumption and genetic risk, measured by polygenic risk score (PRS). CONCLUSIONS: Based on current research evidence, tea consumption, may be a simple and important measure for CI prevention.

[Estrogen, estrogen receptor and miR-21 in adenomyosis: their pathogenic roles and regulatory interactions].

OBJECTIVE: To explore the pathogenic roles of miR-21, estrogen (E2), and estrogen receptor (ER) in adenomyosis. METHODS: We examined the expression levels of miR-21 in specimens of adenomyotic tissue and benign cervical lesions using qRT-PCR. In primary cultures of cells isolated from the adenomyosis lesions, the effect of ICI82780 (an ER inhibitor) on miR-21 expression levels prior to E2 activation or after E2 deprivation were examined with qRT-PCR. We further assessed the effects of a miR-21 mimic or an inhibitor on proliferation, apoptosis, migration and autophagy of the cells. RESULTS: The expression level of miR-21 was significantly higher in adenomyosis tissues than in normal myometrium (P < 0.05). In the cells isolated from adenomyosis lesions, miR-21 expression level was significantly higher in E2 activation group than in ER inhibition + E2 activation group and the control group (P < 0.05); miR-21 expression level was significantly lower in cells in E2 deprivation+ER inhibition group than in E2 deprivation group and the control group (P < 0.05). The adenomyosis cells transfected with miR-21 inhibitor showed inhibited proliferation and migration, expansion of mitochondrial endoplasmic reticulum, increased lysosomes, presence of autophagosomes, and increased cell apoptosis, while transfection of the cells with the miR-21 mimic produced the opposite effects. CONCLUSION: MiR-21 plays an important role in promoting proliferation, migration, and antiapoptosis in adenomyosis cells by altering the cell ultrastructure, which may contribute to early pathogenesis of the disease. In addition to binding with E2, ER can also regulate miR-21 through other pathways to participate in the pathogenesis of adenomyosis, thus having a stronger regulatory effect on miR-21 than E2.

The influence of respiratory movement on preoperative CT-guided localization of lung nodules.

AIM: To evaluate the motion amplitude of lung nodules in different locations during preoperative computed tomography (CT)-guided localization, and the influence of respiratory movement on CT-guided percutaneous lung puncture. MATERIALS AND METHODS: A consecutive cohort of 398 patients (123 men and 275 women with a mean age of 53.9 ± 10.7 years) who underwent preoperative CT-guided lung nodule localization from May 2021 to Apr 2022 were included in this retrospective study. The respiratory movement-related nodule amplitude in the cranial-caudal direction during the CT scan, characteristics of patients, lesions, and procedures were statistically analyzed. Univariate and multivariate logistic regression analyses were used to evaluate the influence of these factors on CT-guided localization. RESULTS: The nodule motion distribution showed a statistically significant correlation within the upper/middle (lingular) and lower lobes (p<0.001). Motion amplitude was an independent risk factor for CT scan times (p=0.011) and procedure duration (p=0.016), but not for the technical failure rates or the incidence of complications. Puncture depth was an independent risk factor for the CT scan times, procedure duration, technical failure rates, and complications (p<0.01). Female, prone, and supine (as opposed to lateral) positions were significant protective factors for pneumothorax, while the supine position was an independent risk factor for parenchymal hemorrhage (p=0.025). CONCLUSION: Respiratory-induced motion amplitude of nodules was greater in the lower lobes, resulting in more CT scan times/radiation dose and longer localization duration, but showed no statistically significant influence on the technical success rates or the incidence of complications during preoperative CT-guided localization.

[Clinical characteristics and associated factors of mild cognitive impairment in patients with common cardiovascular diseases].

Objective: To analyze the clinical characteristics of patients with common cardiovascular diseases (CVD, including hypertension, coronary heart disease, atrial fibrillation, and heart failure) combined with mild cognitive impairment (MCI) and explore the potential risk factors of MCI in patients with CVD. Methods: A total of 2 294 patients with common cardiovascular diseases who met the criteria at Cardiology Medical Center in Beijing Anzhen Hospital, Capital Medical University, from June 1, 2021, to January 5, 2022, were retrospectively included. The patients were divided into the normal cognitive function group (1 107 cases) and the MCI group (1 187 cases). Demographic information and CVD status were collected. The information of cognitive function were collected using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) scales. The difference between normal cognitive function and MCI were compared and analyzed. The logistic regression analysis was used to explored risk factors of MCI in CVD patients. Results: A total of 2 294 patients aged (60.6±10.4) years were included, among whom there were 29.99% (688 cases) females. Compared with patients in the normal cognitive function group, patients in the MCI group were older [ (57.9±11.4) vs (63.1±8.9) years old, P<0.001], with a higher proportion of women [26.47% (293 cases) vs 33.28% (395 cases), P<0.001]; there was a higher proportion of patients suffering from hypertension in the MCI group [59.62% (660 cases) vs 64.62% (767 cases), P=0.014ï¼½, and more components of CVD [(1.68±0.62) vs (1.74±0.65) components, P=0.017]. The risk factors of MCI in patients with common CVD were increased age, increased depression score, combined with hypertension, and ≥3 common components of CVD, with OR (95%CI) of 1.043 (1.032-1.054), 1.021 (1.004-1.037), 1.151 (1.142-3.439), and 1.137 (1.023-1.797), respectively (all P values <0.05). Increasing education level was observed to be associated with reduced risk of MCI with OR (95%CI) of 0.319 (0.271-0.378) (P<0.05). Conclusions: The incidence of MCI was high in CVD patients. The risk factors of MCI in CVD patients included hypertension and≥3 common components of CVD.

Tislelizumab, a novel PD-1 monoclonal antibody in urothelial cancer: A real-world study.

OBJECTIVE: Tislelizumab, a monoclonal antibody against programed death protein-1 (PD-1), has shown encouraging antitumor activity in urothelial cancer. This study was designed to assess the efficacy and safety of tislelizumab in urotelial cancer in a real-world setting. METHODS: The study was a real-world retrospective study undertaken at Liaoning Cancer Hospital & Institute, China. Eligible patients were ≥18 years. Patients received 200-mg tislelizumab monotherapy intravenously every 3 weeks until the disease progressed to intolerable toxicity. Outcomes included an objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Between March 2020 and December 2022, 33 patients were enrolled. The median follow-up was 10.17 (IQR 5.73-12.47) months. Of all 33 patients, ORR and DCR were 30.30% (95% CI 15.6%-48.7%) and 42.42% (95% CI 25.48%-60.78%), respectively. The median PFS was 5.73 (95% CI 3.27-13.00) months, with a 12-month PFS rate of 31.90% (95% CI 19.20%-53.00%). The median OS was 17.7 (95% CI 12.80-not reach) months, with a 12-month OS rate of 67.50% (95% CI 52.70%-86.40%). Eleven (33.33%) and 8 (24.24%) experienced ≥grade 3 treatment-related adverse events (TRAEs) and immune-related Aes, respectively. No treatment-related deaths occurred. CONCLUSION: The excellent efficacy and controllable safety of tislelizumab in locally advanced or metastatic urothelial cancer suggest that it may be a promising therapeutic option for this population.

[Risk analysis of gastrointestinal bleeding in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention].

Objective: Of all spontaneous bleeding complications in patients with acute ST-elevation myocardial infarction (STEMI), upper gastrointestinal bleeding (UGIB) is the most common and of specific interest, because it can be prevented by several prophylactic measures. The purpose of this study was to investigate the in-hospital incidence, associated outcomes, and predictors of UGIB after STEMI. Methods: In this retrospective study, we analyzed the records of 2 791 patients with acute STEMI admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University between January 2018 and January 2022. The patients were divided into the UGIB group (n=61) and non-UGIB group (n=2 730) according to the presence or absence of upper gastrointestinal hemorrhage, respectively. Baseline clinical conditions, coronary lesions, in-hospital deaths, and in-hospital adverse events were compared between the two groups. Logistic regression analysis was also performed for risk factors that could lead to UGIB. Results: The in-hospital incidence of UGIB after STEMI was 2.2% (61/2 791). Hospital stay was significantly longer in the UGIB group [8(6, 12) days vs. 5 (4, 7) days, Z=3.28, P<0.001] and in-hospital mortality was significantly higher in the UGIB group than in the non-UGIB group (9.8% vs. 0.8%, χ2=0.63, P=0.001). Patients with UGIB were significantly older than those without UGIB (63±11 years vs. 58±11 years, t=-3.75, P<0.001). The serum creatinine level of UGIB patients was significantly higher than that of non-UGIB patients [(80(62, 98) mmol/L vs. 73(64, 84) mmol/L, Z=1.68, P=0.007], the red blood cell count of UGIB patients was significantly lower than that of non-UGIB patients [4.1(3.8, 4.6)×1012/L vs. 4.6(4.2, 4.9)×1012/L, Z=2.61,P<0.001], and the hemoglobin concentration of UGIB patients was significantly lower than that of non-UGIB patients [129(109, 141) g/L vs. 141(130, 152) g/L, Z=2.52,P<0.001]. Brain natriuretic peptide levels were significantly higher in UGIB patients than in non-UGIB patients [331(165, 644) ng/L vs. 181(89, 333) ng/L, Z=2.42,P<0.001]. Logistic regression analysis showed that age (OR=1.045, 95%CI 1.009-1.082, P=0.013); hemoglobin (OR=1.594, 95%CI 1.150-2.210, P=0.005); hematocrit (OR=0.181, 95%CI 0.060-0.546, P=0.002); and mean hemoglobin concentration (OR=0.845, 95%CI 0.752-0.951, P=0.005) were independent risk factors for UGIB in patients with STEMI. Logistic regression analysis of risk factors for in-hospital death revealed that concurrent UGIB was an independent risk factor for in-hospital death in patients with STEMI (OR=2.954, 95%CI 0.635-13.751, P=0.024). Conclusions: The incidence of in-hospital UGIB in STEMI patients was 2.2%, and the in-hospital mortality rate of STEMI complicated with UGIB increased to 9.8%. Concurrent UGIB was an independent risk factor for in-hospital death in patients with STEMI. The most important predictors of in-hospital UGIB in patients with STEMI were age, hemoglobin, hematocrit, and mean hemoglobin concentration.

[The Japanese emperors' view of epidemic and medical relief in the 8th-10th centuries].

At the end of the 7th century, Chinese medicine was widely spread in the upper class of Japanese society, and Japanese emperors developed a medical based view on epidemics. At the beginning of the 8th century, emperors determined to reform by imitated the Tang to build a state ruled by law.They determine the way of TCM to relieve the epidemic in the form of legislation, and used medical measures in outbreaks on many occasions.However, with the spread of smallpox and other epidemics during the Tenpei year, Japan's backward medical level and poor medical resources were unable to cope with the epidemic, and the emperors turned to the epidemic as calamity. From the late 8th century to the end of 10th century, Japanese emperors responded with Buddhist, Shinto, and Confucian measures. Medical relief gradually became obsolete at the national level. But at the individual level of the emperors, they attached great importance to the use of Chinese medicine for epidemic prevention and treatment, in the mid to late 9th century, medical prevention measures were established in the court through legal means.

[Poisonous substances and geographical distribution of poisoning in hospitalized children based on data from 25 hospitals in China from 2016 to 2020].

Objective: To investigate the poisonous substances and geographical distribution of poisoning in children in China. Methods: A cross-sectional study. The clinical data of 8 385 hospitalized children from January 2016 to December 2020 were extracted from the FUTang Updating Medical Records database. These children aged 0 to 18 years and were admitted due to poisoning. They were grouped according to age (newborns and infants, toddlers, preschoolers, school-age children, adolescents), place of residence (Northeast China, North China, Central China, East China, South China, Southwest China, Northwest China), and mode of discharge (discharge under medical advice, transfer to another hospital under medical advice, discharge without medical advice, death, other). The poisonous substance and causes of poisoning in different groups were analyzed. Results: Among these 8 385 children, 4 734 (56.5%) were male and 3 651 (43.5%) female, with a male-to-female ratio of 1.3∶1. The age was 3 (2, 7) years. The prevalence of poisoning was 51.8% (4 343/8 385) in toddlers, 16.5% (1 380/8 385) in adolescents, 14.8% (1 242/8 385) in preschoolers, 14.4% (1 206/8 385) in school-age children, and 2.5% (214/8 385) in newborns and infants. Drug poisoning accounted for 43.5% (3 649/8 385) and pesticide accounted for 26.8% (2 249/8 385). Drug poisoning was more common in adolescents (684/1 380, 49.6%) and toddlers (2 041/4 343, 47.0%); non-drug poisoning was more common in school-age children (891/1 206, 73.9%), of which carbon monoxide was mainly in newborns and infants (41/214, 19.2%) and food poisoning in children of school age (241/1 206, 20.0%). Regarding regional characteristics, drug poisoning was more frequent in South China (188/246, 64.2%) and non-drug poisoning was more frequent in Southwest China (815/1 123, 72.5%). For drugs, anti-epileptic drugs, sedative-hypnotic drugs and anti-Parkinson's disease drugs had a higher proportion of poisoning in North China (138/1 034, 13.0%) than that in other regions. For non-drug poisoning, pesticides (375/1 123, 33.3%), food poisoning (209/1 123, 18.6%) and contact with poisonous animals (86/1 123, 7.7%) were more common in Southwest China than in other regions; carbon monoxide poisoning was more common in North China (81/1 034, 7.6%) and Northwest China (65/1 064, 6.3%). In Central China, poisoning happened more in toddlers (792/1 295, 61.2%) and less in adolescents (115/1 295, 8.8%) than in other regions. Regarding different age groups, poisoning in adolescent happened more in Northeast China (121/457, 26.5%), North China (240/1 034, 23.2%), and Northwest China (245/1 064, 23.0%). The rate of discharge under medical advice, discharge without medical advice, and mortality rate within the 5 years were 77.0% (6 458/8 385), 20.8% (1 743/8 385), 0.5% (40/8 385), respectively. Conclusions: Poisoning is more common in male and toddlers. Poisonous substances show a regional characteristic and vary in different age groups, with drugs and insecticides as the most common substances.

[Exploration and prospect of the whole course management model of osteoporosis].

Osteoporosis is a chronic progressive bone disease whose prevalence has increased significantly in China. Fragility fractures caused by osteoporosis pose a heavy burden on patients and their families. Therefore, early and efficient whole course management of osteoporosis is imperative. However, there are great challenges currently in the whole course management of osteoporosis, including lack of disease awareness, low rates of diagnosis and treatment, as well as poor patient compliance. As there is no consensus on the whole course management path to follow in clinical practice, this review analyzes the key points of whole course management of osteoporosis, such as the risk identification of fragility fracture, diagnosis and differential diagnosis, selection of initial treatment drugs, sequential or combined treatment and evaluation of treatment response etc. Based on the current management modes, including fracture liaison service, this review explores the whole course management path of osteoporosis which is suitable for China, including the whole course management ideas and implementation steps, establishing a platform to connect hospitals, communities, and families by application of information technology, developing an innovative system and mechanism indicates that the general practitioner will be responsible for clinical management and follow-up under instruction of clinical osteoporosis specialists, providing the community liaison service, organizing patient education activities such as bone health clubs, ultimately achieving a closed-loop communication among osteoporosis specialist, general practitioner, and patient, so that patients can benefit from it.

Qiliqiangxin capsule improves cardiac remodeling in rats with DOCA-salt-induced diastolic dysfunction.

OBJECTIVE: The aim of this study was to investigate the protective effect and mechanism of action (MOA) of Qiliqiangxin capsule (QL) in the deoxycorticosterone acetate (DOCA) salt-induced rat heart failure with preserved ejection fraction (HFpEF) model. MATERIALS AND METHODS: Nono-nephrectomy sixty Sprague Dawley (SD) rats received DOCA salt injection and 1% saline in drinking water for 4 weeks and were randomly divided into four groups on average: Model group (n=15), Sac/Val group (Sacubitril Valsartan 0.02 g/kg, n=15), QL-L group (Qiliqiangxin 0.25 g/kg, n=15) and QL-H group (Qiliqiangxin 1 g/kg, n=15). Another Normal group was set (n=15). Blood pressure, N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac index, echocardiography, and hemodynamics were measured to evaluate heart function. Masson and Wheat germ agglutinin (WGA) staining was performed to observe the fibrosis deposition and the cross-sectional area (CSA) of cardiomyocytes. The concentration levels of the serum cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and IL-10 inflammatory factors, were detected by ELISA; matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), transforming growth factor-ß1 (TGF-ß1), nuclear factor-κB (NF-κB), Smad homologue 2 (Smad2) and Smad homologue 3 (Smad3) expression were detected by Western-blot. RESULTS: Compared with the Model group, QL treatment significantly ameliorated the heart function in DOCA salt-induced rat HFpEF model, showing a decrease in cardiac index, an increase of the EF and E/A ratio, a reduction in the left ventricular anterior/posterior wall (LVAW/LVPW), in the time contraction of isovolumic diastolic time (IVRT), -dP/dt Max, and Tau, and the decrease of serum NT-ProBNP. Masson and WGA staining indicated that QL inhibited the fibrosis deposition and the myocardial hypertrophy compared with the Model group, which was consistent in reducing the protein expression levels of cardiac remodeling such as TGF-ß1, MMP2, MMP9, Smad2, and Smad3. Moreover, QL treatment inhibited the expression of NF-κB in the heart tissues and decreased the serum concentration of pro-inflammatory cytokines TNF-α and IL-2, instead, increasing the IL-10 concentration. CONCLUSIONS: QL improved the cardiac function and inhibited the myocardial fibrosis in DOCA salt-induced rat HFpEF by improving diastolic dysfunction, preventing left ventricular hypertrophy, and ameliorating the inflammatory responses model in DOCA salt-induced rat HFpEF model.

[Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research].

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

[Analysis of factors influencing the success rate of organoid culture in 1231 cases of colorectal cancer].

Objective: To investigate the risk factors for organoid culture failure in colorectal cancer. Methods: This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples. Results: The median (range) duration of organoid culture was 7 (3-12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant (P=0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P>0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ2=10.773, P=0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ2=7.134, P=0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335-0.924, P=0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285-0.820, P=0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154-63.131,P=0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112-61.882, P=0.039) were identified as independent protective factors. Conclusions: The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.

The Oral Microbiome and Cross-Kingdom Interactions during Pregnancy.

Pregnancy initiates a temporary transition in the maternal physiological state, with a shift in the oral microbiome and a potential increase in frequency of oral diseases. The risk of oral disease is higher among populations of Hispanic and Black women and those with lower socioeconomic status (low SES), demonstrating a need for intervention within these high-risk populations. To further our understanding of the oral microbiome of high-risk pregnant women, we characterized the oral microbiome in 28 nonpregnant and 179 pregnant low-SES women during their third trimester living in Rochester, New York. Unstimulated saliva and supragingival plaque samples were collected cross-sectionally, followed by assessment of the bacterial (16S ribosomal RNA) and fungal (18S ITS) microbiota communities. Trained and calibrated dentists performed oral examinations to determine the number of decayed teeth and plaque index. Initially, plaque from 28 nonpregnant women and 48 pregnant women were compared; these data showed significant differences in bacterial abundances based on pregnancy status. To further our understanding of the oral microbiome within the pregnant population, we next examined the oral microbiome within this population based on several variables. Streptococcus mutans, Streptococcus oralis, and Lactobacillus were associated with a greater number of decayed teeth. The composition of fungal communities differed between plaque and saliva, demonstrating 2 distinct "mycotypes" that were represented by a greater abundance of Candida in plaque and Malassezia in saliva. Veillonella rogosae, a common oral bacterium, was negatively associated with both plaque index and salivary Candida albicans colonization by culture data. This was further emphasized by in vitro inhibition of C. albicans by V. rogosae. Identification of interactions between the bacterial or fungal oral communities revealed that V. rogosae was positively associated with the oral commensal Streptococcus australis and negatively with the cariogenic Lactobacillus genus, suggesting V. rogosae as a potential biomarker of a noncariogenic oral microbiome.

[Pharmacogenetic testing improves treatment responses in patients with PLA2R-related membranous nephropathy].

OBJECTIVE: To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients. METHODS: A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment. RESULTS: Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05). CONCLUSION: Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.