Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population. Methods A prospective cohort study was conducted, enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007. The follow-up period was (8.6±4.0) years. Participants were categorized into four groups based on their baseline blood pressure levels: normal blood pressure (systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg), elevated blood pressure (systolic blood pressure 120-130 mmHg and diastolic blood pressure <80 mmHg), stage 1 hypertension (systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg), and stage 2 hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg). The incidence density of chronic kidney disease (CKD) was compared among these groups. A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients, with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model. Sensitivity analysis was conducted after excluding cases of cardiovascular disease (CVD) during follow-up, and cases using antihypertensive and antidiabetic medications at baseline. Results (1) At baseline, stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index (BMI) compared to normal blood pressure group (P<0.05). (2) By the end of the follow-up, 2 294 cases of CKD were identified, including 1 117 cases of estimated glomerular filtration rate (eGFR) decline and 1 575 cases of urinary protein. The incidences density of CKD, eGFR decline and urinary protein for stage 1 hypertension group were 39.4, 16.3 and 25.5 per thousand person-years, respectively, all of which were statistically significant different from normal blood pressure group (log-rank test, P<0.01). (3) Multivariate Cox regression analysis revealed that, compared to the normal blood pressure group, stage 1 hypertension was associated with a 29% increased risk of CKD (HR=1.29, 95%CI 1.09-1.52) and a 40% increased risk of eGFR decline (HR=1.40, 95%CI 1.08-1.80) in diabetic individuals. Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals, with a particularly notable effect on the risk of eGFR decline.

Objective To investigate the causal relationship between obstructive sleep apnea (OSA) and hypertension using bidirectional Mendelian randomization (MR). Methods Genetic data for OSA were obtained from the Genome-wide association study (GWAS) of FinnGen Biobank, including 16 761 cases and 201 194 controls, from which 5 single-nucleotide polymorphisms (SNPs) were screened as instrumental variables (IVs) for OSA. Genetic data for hypertension were obtained from GWAS of UK Biobank, including 124 227 cases and 337 653 controls from which 214 SNPs were selected as IVs for hypertension. Multiple MR methods, mainly Inverse variance weighted (IVW), were used for analysis. Sensitivity analysis of MR results was performed using MR-Egger regression et al, and IVs were evaluated using F values. Results OSA was associated with an increased risk of hypertension (OR=1.053, 95%CI 1.019-1.089, P<0.01), and hypertension was significantly associated with the risk of developing OSA (OR=1.812, 95%CI 1.354-2.425, P<0.001). Heterogeneity was observed in both two-way outcomes (OSA→ hypertension, P<0.001; hypertension→ OSA, P<0.001), but no evidence of horizontal pleiotropy was detected (OSA→ hypertension, P=0.666; hypertension→ OSA, P=0.556). The IVs selected in this study were strong instrumental variables for both OSA and hypertension (OSA-IVs F=14.695; hypertension-IVs F=39.624). Conclusions Our findings indicate a bidirectional causal relationship between OSA and hypertension, with a particularly significant effect of hypertension on the development of OSA.

Objective To explore the application effect of opioid-free postoperative patient-controlled analgesia strategy in thoracic endoscopic resection of lung lesions. Methods This study is a single center, double-blind, prospective, open label, randomized controlled trial. Ninety patients with lung surgery under thoracic endoscope in the Second Affiliated Hospital of Chongqing Medical University were selected from November 2021 to April 2023, and divided into three groups, according to the random number table method including esketamine and dexmedetomidine (esKDex group, n=30), sufentanil and dexmedetomidine (sFDex group, n=30) and tramadol and dexmedetomidine (TraDex group, n=30). The incidence of postoperative nausea and vomiting (PONV), vital signs related indicators, visual analogue scale (VAS) score, Ramsay sedation (RSS) score, Bruggrmann comfort scale (BCS) score and mini-mental state examination (MMSE) score were compared among the 3 groups within 48 hours after surgery. Results Within 48 h after surgery, the incidence of PONV in esKDex group was lower than that in sFDex group and TraDex group [10.0%(3/30) vs. 20.0%(6/30) vs. 20.0%(6/30), P<0.001]. The VAS scores in esKDex group and sFDex group at 2 h and 4 h after surgery were lower than those in TraDex group (2 h after surgery: P=0.001, 0.001; 4 h after surgery: P=0.027, 0.024). The VAS scores at 24 h and 48 h after surgery were higher than those in TraDex group (24 h after surgery: P=0.008, 0.029; 48 h after surgery: P=0.005, 0.005). The BCS scores of esKDex group and sFDex group at 24 h and 48 h after surgery were lower than those in TraDex group (24 h after surgery: P=0.017, 0.007; 48 h after surgery: P=0.005, 0.007). There was no significant difference between Ramsay scores and MMSE scores among the three groups within 48 h after surgery (P>0.05). Conclusion The strategy of opioid-free postoperative patient-controlled analgesia (esketamine and dexmedetomidine) can reduce the incidence of PONV under the premise of satisfying the sedation and analgesia of patients after thoracic endoscopic surgery.

Objective To report the clinicopathological features, gene mutation sites, diagnosis and treatment of a case of hereditary myopathy with early respiratory failure (HMERF), and review the literature to enhance the understanding of the disease. Methods A retrospective analysis was conducted on the clinical data, imaging examinations, histopathological and genetic sequencing results, as well as the diagnosis and treatment of a case of HMERF as the initial presenting symptom, admitted to Sichuan Provincial People's Hospital in April 2021. The clinical characteristics of Chinese patients with HMERF were summarized in conjunction with literature reports. Results This patient presented with limb weakness and progressive dyspnea. Magnetic resonance imaging (MRI) showed selective fat infiltration of the medial head of calf gastrocnemius muscle. Two mutation sites in titin (TTN) gene inherited from both parents were identified, exon 341 c.94828G>A (P.a31610t) and exon 50 c.14915C>T (P.S.4972L), leading to the diagnosis of HMERF. The patient received supportive therapy. The PubMed database was searched and 15 cases of HMERF were diagnosed in Chinese patients over the past decade. The onset age of these patients was (26.1±17.0) years, predominantly affecting males. All patients exhibited mutations in TTN gene. The most prevalent mutation was identified as c.95195C>T (p.P31732L), followed by c.95134T>C (p.C31712R). Conclusions HMERF is a rare genetic disease caused by genetic mutation, with skeletal muscle weakness and respiratory muscle weakness as the main clinical manifestations. Clinical symptoms can be atypical, and exon 344 of TTN gene is a common mutation site. The mutation sites in this case, located at exon 341 c.94828G>A (P.a31610t) and exon 50 c.14915C>T (P.S4972L) of the TTN gene, may represent novel genetic markers for HMERF.

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms. Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) database from 2008 to 2019. According to the occurrence of posttraumatic fatal massive hemorrhage, the patients were divided into two groups: fatal massive hemorrhage group (n=283) and non-fatal massive hemorrhage group (n=7239). Six machine learning algorithms, including logistic regression (LR), support vector machine (SVM), random forests (RF), adaptive boosting (AdaBoost), gated recurrent unit (GRU), and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma. The probability of fatal massive hemorrhage in the following 1, 2, and 3 h was dynamically predicted. The performance of the models was evaluated by accuracy, sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under receiver operating characteristic curve (AUC). The models were externally validated based on the trauma database of the Chinese PLA General Hospital. Results In the MIMIC-Ⅳ database, the set of dynamic prediction models based on the GRU-D algorithm was the best. The AUC for predicting fatal major bleeding in the next 1, 2, and 3 h were 0.946±0.029, 0.940±0.032, and 0.943±0.034, respectively, and there was no significant difference (P=0.905). In the trauma dataset, GRU-D model achieved the best external validation effect. The AUC for predicting fatal major bleeding in the next 1, 2, and 3 h were 0.779±0.013, 0.780±0.008, and 0.778±0.009, respectively, and there was no significant difference (P=0.181). This set of models was deployed in a public web calculator and hospital emergency department information system, which is convenient for the public and medical staff to use and validate the model. Conclusion A set of dynamic prediction models has been successfully developed and validated, which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

Objective To explore the effects of 1α,25-dihydroxyvitamin D₃ on airway inflammation in asthmatic mice and the potential mechanisms. Methods Twenty-four female BALB/c mice in SPF grade were randomly divided into three groups (n=8): control group, asthma group, and asthma+VD₃ group. On the 1st, 8th, and 15th day, asthma group and asthma+VD₃ group were given 0.2 ml ovalbumin (OVA) suspension for sensitization, while control group received 0.2 ml normal saline. On the 22-28th day, asthma group and asthma+VD₃ group were challenged with 1% OVA atomization inhalation, while control group received an equal amount of normal saline atomization, for 30 minutes each time, once a day, for a continuous 7 days. Asthma+VD₃ group was given intraperitoneal injection of 1α,25-dihydroxyvitamin D₃ injection (4 μg/kg) 30 minutes before each atomization, while control group and asthma group were given an equal dose of normal saline. After the last challenge, all mice were anesthetized, and serum, bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. HE staining and Periodic Acid Schiff (PAS) staining were used to observe the pathological changes in lung tissue and changes in airway mucus levels. ELISA was employed to detect serum IgE and inflammatory cytokines IL-4, IL-5 and IL-13 in BALF. Immunohistochemical technique and Western blotting were used to detect the expressions of SIRT1 and GATA-3 in mouse lung tissue. Results Compared with control group, asthma group had a significant increase in inflammatory cell infiltration around lung tissue, bronchia and accompanying perivascular, mainly characterized by eosinophils. Bronchial lumen stenosis, airway mucosal epithelial hyperplasia, and increased tracheal mucus secretion were also observed. The above changes in asthma+VD₃ group were reduced compared with asthma group. Compared with control group, serum levels of IgE, and IL-4, IL-5, IL-13 inflammatory factors in BALF and GATA-3 in lung tissue were increased in asthma group (P<0.05), and SIRT1 level in lung tissue was significant decreased (P<0.05). Compared with asthma group, IgE level in serum, inflammatory factors of IL-4, IL-5 and IL-13 in BALF, and GATA-3 in lung tissue in asthma+VD₃ group were decreased (P<0.05), and SIRT1 level in lung tissue was increased (P<0.05). Correlation analysis showed that the expression level of lung tissue SIRT1 was negatively correlated with the expression of GATA-3, serum IgG, and the levels of IL-4, IL-5, and IL-13 in BALF (P<0.05); the expression level of lung tissue GATA-3 was positively correlated with serum IgG and the levels of IL-4, IL-5, and IL-13 in BALF (P<0.05). Conclusion 1α,25-dihydroxyvitamin D₃ can alleviate airway inflammation in asthmatic mice, possibly by upregulating the expression of SIRT1 in lung tissue and inhibiting the expression of GATA-3, thereby inhibiting inflammatory factors (IL-4, IL-5, IL-13).

Objective To investigate the effect of vascular endothelial growth factor (VEGF) on the expression of genes related to ovarian steroid synthesis in mice and its underlying mechanism. Methods A transgenic mouse model with tetracycline -reversible regulation of VEGF expression was used, and the genotype of mice was identified by polymerase chain reaction (PCR). Twenty mice were divided into normal VEGF expression group (Dox⁺, n=10) and VEGF expression inhibition group (Dox^-, n=10) by feeding them doxycycline. Western blotting was used to detect the expression of VEGF protein in ovarian tissues. Fluorescence quantitative PCR was used to detect the mRNA expression of VEGF, KDR and genes known to play roles in follicle development, such as follicle-stimulating hormone (FSH) and inhibin B (INHBB). HE staining was used to observe changes in ovarian tissue. Total RNA was extracted from mouse ovarian tissues for transcriptome sequencing, and the relevant differential genes were analyzed by FPKM and log₂FC values. Results Compared with the Dox⁺ group, the mRNA and protein levels of VEGF in the Dox^- group significantly reduced, and the mRNA levels of KDR also significantly decreased (P<0.05). HE staining results showed that compared with the Dox⁺ group, follicular development was impaired and atresia follicles appeared in the Dox^- group. Sequencing analysis identified that significant differences in follicular development-related genes and steroid synthesis-related genes between the two groups (P<0.05). Enrichment analysis showed that VEGF in mouse ovaries mainly regulates ovarian steroidogenesis and other pathways. Fluorescence quantitative PCR results demonstrated that compared with the Dox⁺ group, the follicular development-related genes (INHBB and FSHR) in the ovarian tissues of the Dox^- group were significantly up-regulated (P<0.05), whereas the key genes of steroid synthesis (StAR, CYP11A1, 3β-HSD) were significantly down-regulated (P<0.05).The quantitative results were basically consistent with the sequencing results. Conclusion Mice with inhibited VEGF exhibited ovarian follicular dysplasia, potentially due to the mechanism whereby VEGF inhibition downregulated the expression of genes associated with steroid synthesis, such as FSH and INHBB, thereby obstructing cholesterol metabolism.

Takeda G protein-coupled receptor 5 (TGR5) is a bile acid receptor located on the surface of cell membrane, widely distributed in many tissues and cells in the body, and can be directly activated by most bile acids in vivo. TGR5 plays an important role in various physiological and pathophysiological processes, including cellular Ca²⁺ transport, oxidative stress, cell proliferation, inflammatory responses, and mitochondrial metabolism, thereby maintaining mitochondrial homeostasis and vascular endothelial function, and inhibiting the progression of cardiovascular diseases such as atherosclerosis, myocardial hypertrophy, and cardiac remodeling after myocardial infarction. Currently, with the gradual clinical application of numerous bile acid and bile acid derivatives drugs, it is necessary to further investigate the role of TGR5 in the cardiovascular system, which is an important basis for clinical application of these new drugs. This review discusses the relationship between TGR5 and cardiovascular system from five perspectives: TGR5's involvement in regulating macrophages, endothelial function, vascular smooth muscle cells, cardiomyocytes, and mitochondrial metabolism. It summarizes the recent research progress, aiming to provide the theoretical basis for TGR5 as a novel therapeutic target for cardiovascular diseases.

Exertional heat stroke (EHS) is the most serious and life-threatening acute heat-related illness. It can develop from heat-related illnesses, and the prehospital management is a crucial in the diagnosis and treatment of EHS. The prognosis of EHS patients is largely determined by the rapid recognition, effective cooling, and standardized transportation during the prehospital period. Extensive research has demonstrated that medical security personnel still have fatal misconceptions in the prehospital recognition and management of EHS, mainly due to the lack of recognition and inappropriate treatment. This review summarizes the top 10 misconceptions in prehospital recognition and management of EHS, based on domestic and international research findings and combined with practical scenarios. It also provides an accurate prehospital management plan according to the China Expert Consensus on Diagnosis and Treatment of Heatstroke, aiming to reduce or avoid irreversible damage to EHS patients caused by these misunderstandings and to decrease the incidence, disability rate, and mortality rate of EHS.

Objective To investigate the short-term efficacy and safety of chemotherapy induced by nimotuzumab (NTZ) combined with TP regimen and sequential concurrent chemoradiotherapy in patients with epidermal growth factor receptor positive(EGFR-positive) locally advanced nasopharyngeal carcinoma. Methods A total of 48 patients with stage Ⅲ to IV A nasopharyngeal carcinoma in Guizhou Provincial People's Hospital from January 2020 to December 2022 were prospectively enrolled, and were randomized into two groups: NTP (NTZ+docetaxel/albumin-paclitaxel+cisplatin) group and TP (Docetaxel/albumin-paclitaxel+cisplatin) group(24 cases per group) by random number table method. After 2 or 3 cycles of induction chemotherapy in NTP group, NTZ was sequentially used in combination with cisplatin for concurrent chemoradiotherapy. Immunohistochemistry was used to detect the EGFR expression level, exploring EGFR expression intensity and the therapeutic effect of NTZ in NTP group patients. Meanwhile, short-term efficacy, withdrawal rate and toxic side effects were compared between the two groups after induction chemotherapy. Results In NTP group, the positive expression rate of EGFR was 100%, and EGFR expression intensity significantly correlated with the efficacy of NTZ-combined induction therapy (P<0.05). After induction chemotherapy, the objective response rate (ORR) of cervical lymph nodes in NTP group was significantly higher than that in TP group (75% vs. 45.8%, P=0.039). The primary lesion ORR and overall (primary lesion and cervical lymph node) ORR showed no significant difference between the two groups (P>0.05). Comparison of adverse reactions between the two groups during induction therapy: leukopenia and gastrointestinal reaction in NTP group were lower than those in TP group (P<0.05), but rash was higher than those in TP group (P<0.05). There was no significant difference in liver function, hemoglobin and thrombocytopenia between two groups (P>0.05). Conclusions EGFR expression intensity varies in nasopharyngeal carcinoma tissues, with higher levels indicating greater clinical benefit of combined induction therapy with NTZ. NTZ combined with TP induction regimen demonstrates good short-term efficacy and safety for cervical lymph nodes in patients with locally advanced nasopharyngeal carcinoma.