The changing health effects of air pollution exposure for respiratory diseases: a multicity study during 2017-2022.

BACKGROUND: Multifaceted SARS-CoV-2 interventions have modified exposure to air pollution and dynamics of respiratory diseases. Identifying the most vulnerable individuals requires effort to build a complete picture of the dynamic health effects of air pollution exposure, accounting for disparities across population subgroups. METHODS: We use generalized additive model to assess the likely changes in the hospitalisation and mortality rate as a result of exposure to PM2.5 and O3 over the course of COVID-19 pandemic. We further disaggregate the population into detailed age categories and illustrate a shifting age profile of high-risk population groups. Additionally, we apply multivariable logistic regression to integrate demographic, socioeconomic and climatic characteristics with the pollution-related excess risk. RESULTS: Overall, a total of 1,051,893 hospital admissions and 34,954 mortality for respiratory disease are recorded. The findings demonstrate a transition in the association between air pollutants and hospitalisation rates over time. For every 10 µg/m3 increase of PM2.5, the rate of hospital admission increased by 0.2% (95% CI: 0.1-0.7%) and 1.4% (1.0-1.7%) in the pre-pandemic and dynamic zero-COVID stage, respectively. Conversely, O3-related hospitalization rate would be increased by 0.7% (0.5-0.9%) in the pre-pandemic stage but lowered to 1.7% (1.5-1.9%) in the dynamic zero-COVID stage. Further assessment indicates a shift of high-risk people from children and young adolescents to the old, primarily the elevated hospitalization rates among the old people in Lianyungang (RR: 1.53, 95%CI: 1.46, 1.60) and Nantong (RR: 1.65, 95%CI: 1.57, 1.72) relative to those for children and young adolescents. Over the course of our study period, people with underlying diseases would have 26.5% (22.8-30.3%) and 12.7% (10.8-14.6%) higher odds of having longer hospitalisation and over 6 times higher odds of deaths after hospitalisation. CONCLUSIONS: Our estimates provide the first comprehensive evidence on the dynamic pollution-health associations throughout the pandemic. The results suggest that age and underlying diseases collectively determines the disparities of pollution-related health effect across population subgroups, underscoring the urgency to identifying the most vulnerable individuals to air pollution.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

Cypermethrin induces Sertoli cell apoptosis through endoplasmic reticulum-mitochondrial coupling involving IP3R1-GRP75-VDAC1.

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1). TM4 were cultured with different concentrations of CYP. Flow cytometry, calcium (Ca2+) fluorescent probe, transmission electron microscopy and confocal microscopy, and western blot were to examine apoptosis of TM4, mitochondrial Ca2+, ER-mitochondria coupling, and expressions of related proteins. CYP was found to increase apoptotic rates of TM4 significantly. CYP was shown to significantly increase expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP). Concentration of mitochondrial Ca2+ was increased by CYP treatment significantly. CYP significantly enhanced ER-mitochondria coupling. CYP was shown to increase expressions of IP3R, Grp75 and VDAC1 significantly. We suggest that CYP induces apoptosis in TM4 cells by facilitating mitochondrial Ca2+ overload regulated by ER-mitochondria coupling involving IP3R1-GRP75-VDAC1. This study identifies a novel mechanism of CYP-induced apoptosis in Sertoli cells.

Renal Clearable Nanodots-Engineered Erythrocytes with Enhanced Circulation and Tumor Accumulation for Photothermal Therapy of Hepatocellular Carcinoma.

Living cell-mediated nanodelivery system is considered a promising candidate for targeted antitumor therapy; however, their use is restricted by the adverse interactions between carrier cells and nanocargos. Herein, a novel erythrocyte-based nanodelivery system is developed by assembling renal-clearable copper sulfide (CuS) nanodots on the outer membranes of erythrocytes via a lipid fusion approach, and demonstrate that it is an efficient photothermal platform against hepatocellular carcinoma. After intravenous injection of the nanodelivery system, CuS nanodots assembled on erythrocytes can be released from the system, accumulate in tumors in response to the high shear stress of bloodstream, and show excellent photothermal antitumor effect under the near infrared laser irradiation. Therefore, the erythrocyte-mediated nanodelivery system holds many advantages including prolonged blood circulation duration and enhanced tumor accumulation. Significantly, the elimination half-life of the nanodelivery system is 74.75 ± 8.77 h, which is much longer than that of nanodots (33.56 ± 2.36 h). Moreover, the other two kinds of nanodots can be well assembled onto erythrocytes to produce other erythrocyte-based hitchhiking platforms. Together, the findings promote not only the development of novel erythrocyte-based nanodelivery systems as potential platforms for tumor treatment but also their further clinical translation toward personalized healthcare.

Exclusive and Switchable Superoxide Radical Generation by O2 -Capture-Based Electron Transfer and Supramolecular Assembly.

Type-I photosensitizers (PSs) can generate free radical anions with a broad diffusion range and powerful damage effect, rendering them highly desirable in various areas. However, it still remains a recognized challenge to develop pure Type-I PSs due to the inefficiency in producing oxygen radical anions through the collision of PSs with nearby substrates. In addition, regulating the generation of oxygen radical anions is also of great importance toward the control of photosensitizer (PS) activities on demand. Herein, a piperazine-based cationic Type-I PS (PPE-DPI) that exhibits efficient intersystem crossing and subsequently captures oxygen molecules through binding O2 to the lone pair of nitrogen in piperazine is reported. The close spatial vicinity between O2 and PPE-DPI strongly promotes the electron transfer reaction, ensuring the exclusive superoxide radical (O2 •- ) generation via Type-I process. Particularly, PPE-DPI with cationic pyridine groups is able to associate with cucurbit[7]uril (CB[7]) through host-guest interactions. Thus, supramolecular assembly and disassembly are easily utilized to realize switchable O2 •- generation. This switchable Type-I PS is successfully employed in photodynamic antibacterial control.

Isolation of a marine-derived yeast with potential applications in industrial nitrite utilizing.

The nitrite efficient utilization microorganism Wickerhamomyces anomalus RZWP01 was identified. Using nitrite and ammonium as the sole nitrogen source, the nitrogen removal rate of W. anomalus RZWP01 was 97.4% and 87.1%, respectively. W. anomalus RZWP01 grew well in the nitrite medium with glucose or xylose as the only carbon source. However, the W. anomalus RZWP01 cannot live on the nitrite medium with lactose, citric acid, and methanol as the only carbon source. The maximal cell concentration occurred in the nitrite medium with glucose as the only carbon source at a C/N ratio of 20 for 48 h, reaching 8.92 × 108 cell mL-1. W. anomalus RZWP01 was the first reported yeast that can efficiently utilize nitrite. The isolation and identification of W. anomalus RZWP01 enriched the microbial resources of nitrite-degrading microorganisms and provided functional microorganisms for the water treatment of sustainable aquaculture.

Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

Serial circulating tumor DNA profiling predicts tumor recurrence after liver transplantation for liver cancer.

BACKGROUND: Minimal residual disease (MRD) is proposed to be responsible for tumor recurrence. The role of circulating tumor DNA (ctDNA) to detect MRD, monitor recurrence, and predict prognosis in liver cancer patients undergoing liver transplantation (LT) remains unrevealed. METHODS: Serial blood samples were collected to profile ctDNA mutational changes. Baseline ctDNA mutational profiles were compared with those of matched tumor tissues. Correlations between ctDNA status and recurrence rate (RR) and recurrence-free survival (RFS) were analyzed, respectively. Dynamic change of ctDNA was monitored to predict tumor recurrence. RESULTS: Baseline mutational profiles of ctDNA were highly concordant with those of tumor tissues (median, 89.85%; range 46.2-100%) in the 74 patients. Before LT, positive ctDNA status was associated with higher RR (31.7% vs 11.5%; p = 0.001) and shorter RFS than negative ctDNA status (17.8 vs 19.4 months; p = 0.019). After LT, the percentage of ctDNA positivity decreased (17.6% vs 47.0%; p < 0.001) and patients with positive ctDNA status had higher RR (46.2% vs 21.3%; p < 0.001) and shorter RFS (17.2 vs 19.2 months; p = 0.010). Serial ctDNA profiling demonstrated patients with decreased or constant negative ctDNA status had lower RR (33.3% vs 50.0%; p = 0.015) and favorable RFS (18.2 vs 15.0 months, p = 0.003) than those with increased or constant positive ctDNA status. Serial ctDNA profiling predicted recurrence months ahead of imaging evidence and serum tumor biomarkers. CONCLUSIONS: ctDNA could effectively detect MRD and predict tumor recurrence in liver cancer patients undergone LT.

Association between gut microbiota and seven gastrointestinal diseases: A Mendelian randomized study.

BACKGROUND: Observational research has shed light on the ability of gut microbes to influence the onset and progression of gastrointestinal diseases. The causal relationships between specific gut microbiomes and various gastrointestinal conditions, however, remain unknown. METHODS: We investigated the relationship between gut microbiota and seven specific gastrointestinal disorders using a robust two-sample Mendelian randomization (MR) approach. The inverse variance-weighted (IVW) method was used as the primary analysis tool in our study. Furthermore, we conducted multiple sensitivity analyses to strengthen the robustness of our findings and ensure the reliability of the IVW method. RESULTS: Our research has discovered significant links between the composition of gut microbiota and a variety of gastrointestinal ailments. We found compelling links between 13 gut microbiota and fatty liver, four gut microbiota and cirrhosis, eight gut microbiota and hepatocellular carcinoma, four gut microbiota and cholelithiasis, 12 gut microbiota and acute pancreatitis, eight gut microbiota and chronic pancreatitis, and 11 gut microbiota and pancreatic cancer. These findings shed light on the intricate relationship between gut microbes and the emergence of these specific gastrointestinal conditions. CONCLUSIONS: The findings of this extensive study not only validate the potential role of specific gut microbiota in gastrointestinal diseases, but also fill a critical gap in previous research. The discovery of these specific gut microbiota is a significant step forward because they may serve as novel and promising biomarkers for both the prevention and treatment of gastrointestinal conditions.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The associations between high-levels of urine benzophenone-type UV filters (BPs) and changes in serum lipid concentrations.

Little is known about the potential health impacts of benzophenone-type UV filters (BPs) exposure among the general population. In our study conducted in Wuxi, China, we investigated the associations between the concentrations of eight BP-derivatives and five target lipid molecules. We collected basic information, serum, and urine samples from 120 residents aged 9 to 80 in Wuxi. We determined BPs in urine samples and lipid levels in serum samples. Generalized linear models were used to evaluate the differences in ln-transformed serum target lipids levels (µg/L) with different urine BPs quartiles compared to the lowest quartile. Benzophenone-4 (BP-4) had the highest detection rate (95.0%) and geometric mean concentration (1.96 µg/L) among all the BP-derivatives in our study population. The exposure levels of BPs were generally higher in females than in males. Participants in the 9-17 and 18-50 age groups exhibited greater levels of exposure to BPs than those in the 51-80 age group. We observed statistically significant changes in LysoPC (18:0), LysoPE (18:0), ΣLPL, and ΣTL concentrations between the highest and lowest quartiles of BP-4. Similar changes were found in LysoPE (18:0) concentration between the highest and lowest quartiles of ΣBP-3 and ΣBPs. High urine BP concentrations were associated with variations in our target serum lipids involved in neurological and metabolic disorders, and posed a potential health risk. Future studies are warranted to further validate and elucidate our findings.

Artificial intelligence-based diagnosis of standard endoscopic ultrasonography scanning sites in the biliopancreatic system: A multicenter retrospective study.

BACKGROUND: There are challenges for beginners to identify standard biliopancreatic system (BPS) anatomical sites on endoscopic ultrasonography (EUS) images. Therefore, we aimed to develop a convolutional neural network (CNN)-based model to identify standard BPS anatomical sites on EUS images. METHODS: The standard anatomical structures of the gastric and duodenal regions observed by EUS was divided into 14 sites. We used 6230 EUS images with standard anatomical sites selected from 1812 patients to train the CNN model, and then tested its diagnostic performance both in internal and external validations. Internal validation set tests were performed on 1569 EUS images of 47 patients from 2 centers. Externally validated datasets were retrospectively collected from 16 centers, and finally 131 patients with 85,322 EUS images were included. In the external validation, all EUS images were read by CNN model, beginners, and experts, respectively. The final decision made by the experts was considered as the gold standard, and the diagnostic performance between CNN model and beginners were compared. RESULTS: In the internal test cohort, the accuracy of CNN model was 92.1%-100.0% for 14 standard anatomical sites. In the external test cohort, the sensitivity and specificity of CNN model were 89.45%-99.92% and 93.35%-99.79%, respectively. Compared with beginners, CNN model had higher sensitivity and specificity for 11 sites, and was in good agreement with the experts (Kappa values 0.84-0.97). CONCLUSIONS: We developed a CNN-based model to automatically identify standard anatomical sites on EUS images with excellent diagnostic performance, which may serve as a potentially powerful auxiliary tool in future clinical practice.

Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARγ/FABP4 signaling in mice.

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

Single-cell and spatial architecture of primary liver cancer.

Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE+ intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies.

Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Acute pancreatitis and metabolic syndrome: genetic correlations and causal associations.

BACKGROUND: Although there is a definite correlation between the Metabolic Syndrome (MetS) and Acute Pancreatitis (AP), cause is yet unknown. The current work combined linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) approaches to fill this important information gap. METHODS: In this study, we harnessed the power of publicly available gene-wide association databases (GWAS) to explore the intricate relationship between MetS and its components with AP. The cornerstone of our analysis was the Inverse-Variance Weighted (IVW) method, serving as our primary analytical tool. In addition to IVW, we complemented our investigation with several other robust MR methods, including MR-Egger, Weighted Median, Maximum Likelihood, and MR-PRESSO. By employing this diverse set of analytical approaches, we sought to ensure the comprehensiveness and robustness of our findings. RESULT: LDSC regression indicated a genetic correlation between MetS and AP. Univariate MR results indicated a genetic association between MetS (OR = 1.084; 95% CI, 1.005-1.170; P = 0.037), BMI (OR = 1.459; 95% CI, 1.325-1.606; P = 1.46E-14), WHR (OR = 1.189; 95% CI, 1.068-1.323; P = 1.56 E-03), TG (OR = 1.110; 95% CI, 1.001-1.231; P = 0.047), and FI (OR = 1.798; 95% CI, 1.245-2.595; P = 1.74E-03) were able to significantly increase the risk of AP. The results of multivariate MR analysis revealed that these causality associations still existed. CONCLUSION: Our investigation has yielded compelling evidence that substantiates the presence of both a genetic correlation and a causal relationship between MetS and AP.

The role of lncRNA in the pathogenesis of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and irreversible airflow obstruction with abnormal lung function. Because its pathogenesis involves multiple aspects of oxidative stress, immunity and inflammation, apoptosis, airway and lung repair and destruction, the clinical approach to COPD treatment is not further updated. Therefore, it is crucial to discover a new means of COPD diagnosis and treatment. COPD etiology is associated with complex interactions between environmental and genetic determinants. Numerous genes are involved in the pathogenic process of this illness in research samples exposed to hazardous environmental conditions. Among them, Long non-coding RNAs (lncRNAs) have been reported to be involved in the molecular mechanisms of COPD development induced by different environmental exposures and genetic susceptibility encounters, and some potential lncRNA biomarkers have been identified as early diagnostic, disease course determination, and therapeutic targets for COPD. In this review, we summarize the expression profiles of the reported lncRNAs that have been reported in COPD studies related to environmental risk factors such as smoking and air pollution exposure and provided an overview of the roles of those lncRNAs in the pathogenesis of the disease.

Comprehensive evaluation of the effectiveness of endemic disease prevention and control in Jiangsu Province, China, 2013-2022.

As a strong economic and populous province in China, Jiangsu is home to four endemic diseases. Despite efforts in the past decade, the prevention and control of these four endemic diseases are not uniform because of the different etiological chains and influencing factors of these diseases. Among the evaluation methodologies for endemic disease control, only one method is currently available for each disease. In this study, we selected 14 indicators to comprehensively evaluate the effectiveness of endemic disease control in Jiangsu between 2013 and 2022. We improved the method for calculating the weights of the indicators and established a fuzzy comprehensive evaluation model based on the weighted Technique for Order Preference by Similarity to an Ideal Solution model and a weighted grey relational analysis model. The results of the comprehensive evaluation showed that the progress of endemic disease control in Jiangsu was not always in line with our expectations of improvement, with the top five years of better control occurring in 2015, 2013, 2021, 2022, and 2014. The results of the sensitivity analysis confirm the reliability and accuracy of these findings. We discovered that measures such as the reform of the salt industry, use of thyroid ultrasound, and new water supply projects for residents in Jiangsu affected the progress of endemic disease prevention and control. The tracking of endemic disease status should consider the potential effects of changes in policies implemented in other industries on endemic disease prevention and control. Additionally, the results of this study provide a theoretical basis for enhancing prevention and control practices in other regions of China.

Oral diet management for carcinoma at the base of tongue with radiotherapy and chemotherapy associated dysphagia: a case report.

Introduction: Tongue cancer is one of the common malignancy of the head and neck, and directly impacts chewing, swallowing, and other eating activities. Based on the evidence-based guidelines and clinical management, this paper presents nutrition management experience of a patient with tongue cancer who had a dysphagia and feeding reflux while undergoing radiotherapy and chemotherapy. Methods: Nutritional risk screening and comprehensive nutritional assessment were performed based on the patient's medical history, and personalized nutritional programs were developed under the guidance of the clinical pharmaceutical consensus of parenteral nutrition and nutritional treatment guidelines for patients with tumors during radiotherapy. For the management of oral feeding, the patient's swallowing function was evaluated to manage oral feeding. Thickening powders were used to improve the consistency of the patient's food, which successfully achieved oral feeding of the patient. Results: The patient finally ate five meals a day by mouth, and energy requirements were met using industrialized nutritional supplements, and homogenized food was added in between the meals. The energy provided by enteral nutrition can reached approximately 60-75%. The patient's weight and albumin levels had increased significantly at the time of discharge. Discussion: The nutritional management of patients with dysphagia should be jointly managed by clinicians, nurses, nutritionists, and family members to effectively improve the quality of life (QOL) and nutritional status of patients. To ensure adequate nutritional supply, appropriate swallowing training may delay the deterioration of the chewing function and improve the eating experience of such patients.

Rotationplasty type BIIIb as an effective alternative to limb salvage procedure in adults: Two case reports.

BACKGROUND: Rotationplasty is often performed for malignant tumors, but type BIIIb rotationplasty is rarely reported, and there needs to be more evidence of the procedure and treatment. The purpose of this case study was to report a new direction in the use of type BIIIb rotationplasty in treating patients with limb salvage and long-term non-healing infections. CASE SUMMARY: Case 1: A 47-year-old man underwent radiotherapy for hemangioendothelioma in his left thigh, resulting in a femoral fracture. Despite the use of plates, intramedullary nailing, and external fixators, the femoral bone failed to unite due to infectious nonunion. Multiple operations were unable to control the infection, leaving the patient immobile. We performed a modified tibia-pelvic-constrained hip rotationplasty, utilizing a constrained prosthetic hip between the tibia and pelvis following a femur resection. Two years post-surgery, the patient was able to walk with the prosthetic device without any signs of recurring infection. The corresponding functional scores were 72 points for the Musculoskeletal Tumor Society (MSTS), 53 for the Functional Mobility Assessment (FMA), 93 for the Toronto Extremity Salvage Score (TESS), and 56 for the MOS 36-item short form health survey (SF-36). Case 2: A 59-year-old woman presented with liposarcoma in her left thigh. Magnetic resonance imaging revealed tumors in the medial, anterior, and posterior femur muscles, encircling the femoral vessels and nerves. Fortunately, there were no symptoms of sciatic dysfunction, and the tumor had not invaded the sciatic nucleus. After one year of follow-up, the patient expressed satisfaction with limb preservation post-type BIIIb rotationplasty. The corresponding functional scores were 63 points for the MSTS, 47 for the FMA, 88 for the TESS, and 52 for the SF-36. CONCLUSION: Our study suggests that type BIIIb rotationplasty may be an alternative to amputation in patients with incurable infections. For malignant tumors of the lower extremities without invasion of the sciatic nerve, type BIIIb rotationplasty remains an excellent alternative to amputation. This surgical method may prevent amputation, improve functional outcomes, and facilitate biological reconstruction.