Objective To mine adverse drug event(ADE)signals of doxycycline using the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide scientific evidence for clinical medication safety.Methods The data from the FAERS database between the first quarter of 2004 and the first quarter of 2024 were extracted.After data cleaning and standardization,ADE reports with doxycycline as the main suspected drug were screened.The system organ class(SOC)of ADE was performed using MedDRA,and the reporting odds ratio method and Medicines and Healthcare products Regulatory Agency method were used to mine ADE signals.The information component method was also used to evaluate signal strength.Results A total of 43 126 ADE reports with doxycycline as the primary suspected drug were collected,involving 14 642 patients,with a higher proportion of female patients(57.32％).There were 555 related ADE signals involving 26 SOC,with the top 5 SOC being gastrointestinal disorders,skin and subcutaneous tissue disorders,injuries,poisonings,and procedural complications,psychiatric disorders,and infections and infestations.The top 5 ADE signals with the highest signal intensity were Hatch reaction,sclerosing cholangitis,esophageal ulcer,gastrointestinal mucosal necrosis,and gastrointestinal injury.Among the ADE signals with the strongest signal strength not listed in the package insert,the top five were sclerosing cholangitis,nephrogenic diabetes insipidus,minimal change glomerular nephritis,diabetes insipidus and Sixth cranial nerve paralysis.Conclusion In clinical practice,particular attention should be paid to the frequent ADEs caused by doxycycline,as well as those not yet documented in the package insert,which involve multiple SOC such as renal and urinary disorders,hepatobiliary diseases,blood and lymphatic system disorders,and endocrine disorders.Therefore,clinical pharmacists should play a key role in assisting clinicians to develop and implement prevention plans for ADEs,thereby improving the safety of doxycycline in clinical use.

Objective:To evaluate the characteristics, clinical management and clinical outcomes of type 2 intestinal failure (IF).Methods:A descriptive case-control study was carried out. The inclusion criteria were as follows: (1) the diagnosis of IF was performed according to the European Society for Parenteral and Enteral Nutrition (ESPEN) consensus statement. (2) using a requirement for parenteral nutrition (PN) of 28 days or more as surrogate marker. (3) a multidisciplinary team (MDT) included surgeons, nutritionist, pharmacist, stoma therapists, and critical care physicians. (4) complete laboratory data. Patients with type 1 and type 3 IF and those who do not cooperate with follow-up. All the data of 67 type II IF were collected from the database in Sir Run Run Shaw Hospital from Jan 2016 to Dec 2023. The pathophysiology, clinical management, and outcomes of type II IF were analyzed.Results:A total of 67 type II IF were included. The median age was 54 (15-83) with 43 males and 24 females. The body mass index was (17.5±3.8) kg/m 2, the incidence of malnutrition was 67.2% (45/67), the incidence of sarcopenia was 74.6% (50/67), the median number of previous surgeries was 2.0 (1-13), and the median duration time of PN was 2.1 (1-12) months. The underlying disease of type 2 IF included 36 Crohn`s disease, 2 ulcerative colitis, 3 radiation enteritis, 2 intestinal Behcet's disease, 4 mesenteric infarction, 1 aggressive fibromatosis, 5 abdominal cocoon syndrome, 5 gastrointestinal perforation, 1 hernia, 4 intestinal dysmotility, and 4 other reasons (gastrointestinal tumor, trauma, and non-Hodgkin's lymphoma). According to the pathophysiology of IF, there were 33 intestinal fistula, 12 intestinal dysmotility, 6 mechanical obstruction, 13 short bowel syndrome, and 3 extensive small bowel mucosal disease. After treatment with MDT, 67 patients with type 2 IF received nutritional support therapy for intestinal rehabilitation treatment, of which 36 patients recovered with oral diet or enteral nutrition, 31 patients underwent reconstructive surgery after intestinal rehabilitation treatment failure. The median duration time of reconstructive surgery was 2.7 (1-9) months. 24 patients recovered intestinal autonomy after surgery, with 7 deaths, including 6 deaths due to abdominal infections and 1 case of intestinal dysmotility with abiotrophy and liver failure. Conclusion:Standardized multidisciplinary treatment plays an important role in type II intestinal failure, and it promotes patients with intestinal failure regain enteral autonomy.

Objective:To evaluate the characteristics, clinical management and clinical outcomes of type 2 intestinal failure (IF).Methods:A descriptive case-control study was carried out. The inclusion criteria were as follows: (1) the diagnosis of IF was performed according to the European Society for Parenteral and Enteral Nutrition (ESPEN) consensus statement. (2) using a requirement for parenteral nutrition (PN) of 28 days or more as surrogate marker. (3) a multidisciplinary team (MDT) included surgeons, nutritionist, pharmacist, stoma therapists, and critical care physicians. (4) complete laboratory data. Patients with type 1 and type 3 IF and those who do not cooperate with follow-up. All the data of 67 type II IF were collected from the database in Sir Run Run Shaw Hospital from Jan 2016 to Dec 2023. The pathophysiology, clinical management, and outcomes of type II IF were analyzed.Results:A total of 67 type II IF were included. The median age was 54 (15-83) with 43 males and 24 females. The body mass index was (17.5±3.8) kg/m 2, the incidence of malnutrition was 67.2% (45/67), the incidence of sarcopenia was 74.6% (50/67), the median number of previous surgeries was 2.0 (1-13), and the median duration time of PN was 2.1 (1-12) months. The underlying disease of type 2 IF included 36 Crohn`s disease, 2 ulcerative colitis, 3 radiation enteritis, 2 intestinal Behcet's disease, 4 mesenteric infarction, 1 aggressive fibromatosis, 5 abdominal cocoon syndrome, 5 gastrointestinal perforation, 1 hernia, 4 intestinal dysmotility, and 4 other reasons (gastrointestinal tumor, trauma, and non-Hodgkin's lymphoma). According to the pathophysiology of IF, there were 33 intestinal fistula, 12 intestinal dysmotility, 6 mechanical obstruction, 13 short bowel syndrome, and 3 extensive small bowel mucosal disease. After treatment with MDT, 67 patients with type 2 IF received nutritional support therapy for intestinal rehabilitation treatment, of which 36 patients recovered with oral diet or enteral nutrition, 31 patients underwent reconstructive surgery after intestinal rehabilitation treatment failure. The median duration time of reconstructive surgery was 2.7 (1-9) months. 24 patients recovered intestinal autonomy after surgery, with 7 deaths, including 6 deaths due to abdominal infections and 1 case of intestinal dysmotility with abiotrophy and liver failure. Conclusion:Standardized multidisciplinary treatment plays an important role in type II intestinal failure, and it promotes patients with intestinal failure regain enteral autonomy.

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO₂, NO₂, CO, PM_2.5, PM₁₀, and maximum 8 h O₃ concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM_2.5, NO₂, SO₂, and O₃ were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM_2.5, NO₂, SO₂ and O₃ were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Liver fibrosis is a pathological process of fibrous scar formation caused by excessive accumulation of extracellular matrix due to various etiologies. At present, etiological treatment, such as effective antiviral therapy, is still the main treatment strategy for liver fibrosis. As the core participant of liver fibrosis, liver macrophages affect the progression and regression of liver fibrosis and are thus considered an important target for the treatment of liver fibrosis. With the recent advances in the field of immune metabolism, metabolic reprogramming has become a key factor for determining the outcome of macrophages and promoting the development of diseases. This article reviews the role and metabolic changes of macrophages during liver fibrosis and discusses the anti-fibrotic potential of targeting macrophage metabolism, so as to provide new ideas for the development, progression, and treatment of liver fibrosis.

Objective:To analyze the relationship between mesenteric fat or creeping fat and bowel stricture or penetrating disease of Crohn's disease (CD).Methods:Clinical data of 101 CD patients undergoing bowel surgery at Department of General Surgery in our hospital between Mar 2021 and Dec 2021 were retrospectively analyzed. The characteristics of mesenteric fat, creeping fat, luminal cross-section diameter, and the intestinal stricture index were analyzed. The Spearman correlation analysis was used to evaluate the correlation between disease behavior and mesenteric fat score or creeping fat score.Results:Totally 101 CD patients were enrolled, with 68 stricturing diseases and 33 penetrating diseases. CD patients with stricturing diseases had higher score of mesenteric disease activity index (4.6±1.9 vs. 3.7±2.0, t=2.212, P=0.029) and creeping fat index (4.2±2.0 vs. 2.9±1.6, t=3.154, P=0.002) than those in patients with penetrating diseases. The mesenteric fat and creeping fat score positively correlated with the intestinal stricture index, C-reactive protein, and fecal calprotectin, and negatively correlated with minimum luminal cross-section diameter. Conclusion:The higher score of mesenteric fat and creeping fat were observed in CD patients with stricturing disease, which were associated with intestinal stricture index and inflammation status.

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

Background It is projected that the frequency, density, and duration of compound hot extreme may increase in the 21st century in the context of global warming. Objective To explore the association between compound hot extreme and blood pressure, and identify sensitive populations. Methods This was a cross-sectional study. The study subjects were from six Guangdong Province Chronic Disease and Nutrition Surveys during 2002 through 2015. A questionnaire was administered to the participants with questions about demographic information, drinking and smoking status, and measurements on their height, weight, and blood pressure were also collected. We chose the data of May, September, and October to explore the association between compound hot extreme and blood pressure. Compound hot extreme means a hot day with a proceeding hot night. Daily meteorological data were obtained from China Meteorological Data Service Centre. We employed inverse distance weighting to interpolate the temperature and relative humidity values for each participant. A distributed lag non-linear model was used to estimate the association between compound hot extreme and blood pressure. Stratified analyses by sex, age, area, body mass index (BMI), smoking status, and drinking status were also performed to identify sensitive populations. A sensitivity analysis was conducted by adjusting the degrees of freedom for lag spline and removing relative humidity. Result A total of 10967 participants without history of hypertension were included in this study. The average systolic blood pressure (SBP) was 120.8 mmHg and the average diastolic blood pressure (DBP) was 74.5 mmHg. The proportion of participants who experienced hot day, hot night, or compound hot extreme were 9.34%, 17.95% and 2.90%, respectively. Compared to hot day, hot night and compound hot extreme were related with decreased blood pressure, and the effect of compound hot extreme was stronger: the changes and 95%CI for SBP was −6.2 (−10.3-−2.1) mmHg, and for DBP was −2.7 (−5.2-−0.2) mmHg. Compound hot extreme induced decreased SBP among male, population ≥ 65 years, and those whose BMI < 24 kg·m^-2, and their ORs (95%CIs) were −6.2 (−10.7-−1.6). −19.1 (−33.0-−5.1), and −6.7 (−11.8~−1.6) mmHg, respectively, and also decreased DBP among population ≥ 65 years, and its OR (95%CI) was −8.4 (−15.6-−1.1) mmHg. During compound hot extremes, participants living in rural areas showed decreased SBP and DBP, and the ORs (95%CIs) were −10.5 (−16.6-−4.5) and −4.4 (−7.7-−1.1) mmHg respectively, while those living in urban areas showed increased SBP, and the OR (95%CI) was 9.7 (2.9-16.5) mmHg. A significant decrease in blood pressure [OR (95%CI)] was also found in non-smokers [DBP, −3.7 (−6.6-−0.8) mmHg] and non-drinkers [SBP, −4.8 (−9.4-−0.2) mmHg; DBP, −3.4 (−6.0-−0.9) mmHg]. Conclusion Compound hot extreme is negatively associated with SBP, and being male, aged 65 years and over, and having BMI < 24 kg·m⁻² may be more sensitive to compound hot extreme.

Background In recent years, the incidence of metabolic syndrome (MS) is increasing significantly in China. Some studies have found that temperature is related to single metabolic index, but there is a lack of research on associated mechanism and identifying path of the influence of temperature on MS. Objective Based on the data of Guangdong Province, to investigate the effect of temperature on MS and its pathway. Methods A total of 8524 residents were enrolled by multi-stage random sampling from October 2015 to January 2016 in Guangdong. Basic characteristics, behavioral characteristics, health status, and physical activity level were obtained through questionnaires and physical examinations, and meteorological data were obtained from meteorological monitoring sites. We matched individual data both with the temperature data of the physical examination day and of a lag of 14 d. A generalized additive model was used to explore the exposure-effect relationship between temperature and MS and its indexes, calculate effect values, and explore the effects of single-day lag temperature. Based on the literature and the results of generalized additive model analysis, a path analysis was conducted to explore the pathways of temperature influencing MS. Results The association between daily average temperature on the current day or lag 14 day and MS risk was not statistically significant. When daily average temperature increased by 1 ℃, the change values of fasting blood-glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and high density lipoprotein cholesterol (HDL-C) were −0.033 (95%CI: −0.040-−0.026) mmol·L⁻¹, −0.662 (95%CI: −0.741-−0.583) mmHg, −0.277 (95%CI: −0.323-−0.230) mmHg, and −0.005 (95%CI: −0.007-−0.004) mmol·L⁻¹ respectively. The effects of average daily temperature on FBG, blood pressure, HDL-C, and waist circumference lasted until lag 14 day. The effects of daily average temperature on SBP and DBP were the largest on the current day. Daily average temperature of current day had direct and indirect effects on FBG and SBP. Temperature had an indirect effect on TG, and the intermediate variables were waist circumference and FBG, with an indirect effect value of −0.011 (95%CI: −0.020-−0.002). The indirect effects of daily average temperature on SBP, FBG, and TG were weak. Conclusion There is no significant correlation between temperature and risk of MS, and daily average temperature of current day could significantly affected blood pressure and FBG with a lag effect. Daily average temperature of current day has indirect effects on FBG and TG.

Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.