Vitamin D regulates calcium and phosphorus homeostasis, promotes bone growth, development and mineralization, therefore plays an important role in maintaining bone health. In recent years, the extraskeletal effects of vitamin D have received increasing attention with further research. Studies have shown that vitamin D is involved in the occurrence and development of various diseases, and vitamin D deficiency may lead to increased disease risk. However, there is still controversy over whether supplementing vitamin D brings definitely clinical benefits. This article reviews the extraskeletal effects and related mechanisms of vitamin D in obesity, diabetes, cardiovascular diseases, immunoregulation, oncogenesis and sarcopenia, providing information for further study on its biological activities and clinical applications.

Diabetic foot(DF),a primary chronic complication of diabetes mellitus,contributes to a major disability and mortality in diabetic patients.DF is diagnosed mainly depending not only on clinical manifestations,signs,and related inspection,but also on recently emerging diagnostic means:biological markers.Inflammatory biomarkers are preferably used for its superiority in DF early diagnosis.In recently years,thanks to advancements of biological technologies,biomarkers such as procalcitonin(PCT),C-reactive protein(CRP),interleukins(ILs),and tumor necrosis factor-alpha(TNF-α)have been comprehensively used in DF diagnosis.Moreover,biomarkers of genomics,proteomics,metabolomics,and metagenomics have been employed as well.In this review,we aim to com-prehensively review the role of serum biomarkers in DF diagnosis and risk stratification,elaborating on the current research status in applying serum biomarkers for DF prevention,diagnosis,and prognosis assessment.

Objective:To investigate the epidemic status of drinking-tea type endemic fluorosis (fluorosis for short) in Inner Mongolia Autonomous Region (Inner Mongolia for short), and to provide theoretical basis and basic data for formulation and evaluation of prevention and control measures.Methods:From May to October 2022, a cross-sectional survey was conducted in key areas (168 administrative villages in 6 leagues or cities) identified in the 2019 regional census with tea drinking habits, daily per capita intake of tea fluoride > 3.5 mg, and patients with skeletal fluorosis. The drinking condition of brick tea in 10 households of each administrative village was investigated, and the brick tea samples were collected to detect fluoride level. The prevalence of dental fluorosis in children aged 8 - 12 and skeletal fluorosis in adults aged 16 and older was investigated, and urine samples of patients with skeletal fluorosis were collected to detect urinary fluoride levels.Results:Totally 98.40% (1 657/1 684) of the households in the surveyed areas had a habit of drinking brick tea, with an annual per capita consumption of brick tea and a daily per capita intake of tea fluoride of 5.07 kg and 5.38 mg, respectively. The qualified rate of fluoride level in brick tea samples was 55.64% (922/1 657), the average fluoride level of all other brick tea varieties exceeded the national standard limit (300 mg/kg) except for black brick tea (291.08 mg/kg). Totally 2 747 children aged 8 to 12 were examined, with a detection rate of 13.91% (382/2 747) for dental fluorosis. The disease was mainly mild. There was no statistically significant difference in the detection rate of dental fluorosis among different age groups (χ 2 = 5.53, P = 0.238). Totally 71 708 adults aged 16 and older were examined, and the detection rate of skeletal fluorosis was 1.02% (734/71 708). Patients were mainly aged between 50 and 70 years old, and the condition in each age group was mainly mild. Totally 715 urine samples of skeletal fluorosis patients were collected and tested, and 55.24% (395/715) of the urine samples had fluoride levels higher than 1.6 mg/L. Conclusions:In Inner Mongolia, the proportion of high fluoride brick tea in endemic areas of drinking-tea type fluorosis is high. The detection rates of dental fluorosis in children and skeletal fluorosis in adults are relatively high. The prevention and control situation of drinking-tea type fluorosis is still serious.

Objective:To explore the improvement of image quality of different acceleration factors in breath-hold three-dimensional magnetic resonance cholangiopancreatography (3D MRCP) using deep learning (DL) and compressed sensing (CS) technology.Methods:A total of 68 patients who underwent upper abdominal 3D MRCP examination at West China Hospital of Sichuan University from March to August 2023 were prospectively included. The patients were subdivided into three groups randomly with the following paramters: CS group with an acceleration factor of 24 (CS-24); DL-CS group with acceleration factors 24 (DL-CS-24) and 33 (DL-CS-33) respectively. The signal-to-noise ratio (SNR), contrast ratio (CR) and contrast-to-noise ratio (CNR) of the three sets of images were measured, and the overall image quality, background suppression, artifacts, and visibility of bile ducts and pancreatic ducts at all levels were subjectively evaluated. Chi-square test and Friedman test were used to perform statistical analysis on the number of unsatisfactory diagnostic images and subjective and objective indicators of the three groups of sequences respectively.Results:The scanning time of the DL-CS-33 group (9 s) was 30% shorter than that of the CS-24 group and DL-CS-24 group (13s). The images of DL-CS-33 group from 68 patients all met the clinical diagnostic requirements and statistically differences were found between the images from CS-24 group and DL-CS-24 group (all P<0.05). There were no statistically differences in SNR, CR, CNR, overall image quality, artifacts, and visibility scores of bile ducts and pancreatic ducts at all levels between the DL-CS-33 group and the CS-24 group (all P>0.05). The SNR, CR, CNR, intrahepatic bile duct, main pancreatic duct and overall image quality of the DL-CS -24 group were better than those of the CS-24 group (all P<0.05). Conclusions:DL-CS technology could improves breath-hold 3D MRCP image quality with the 24 acceleration factor with no additioanl scanning time. DL-CS technology combined with a high acceleration factor of 33 further reduces scanning time while ensuring overall image quality, providing a fast breath-hold scanning solution.

Objective:To evaluate the repair protocols for intraoperative cerebrospinal fluid (CSF) leaks after endoscopic endonasal clival malignancy resection (EECR) and to analyze the risk factors of surgical complication.Methods:The clinical data of patients who underwent EECR and had intraoperative CSF leaks in XuanWu Hospital, Capital Medical University between January 2012 and January 2024 were reviewed. The pathological results, imaging data, location of the dural defect, degree of intraoperative CSF leaks, repair materials, complications such as postoperative central nervous system (CNS) infections, types of antibiotics used, bacterial culture and drug sensitivity results, secondary repair, and follow-up results were collected. IBM SPSS 26 software was used to evaluate the effectiveness of the repair. Additionally, statistical analysis was conducted on perioperative complications such as CNS infections.Results:Twenty-eight patients underwent 31 EECR and 36 skull base reconstructions. There were 14 females and 14 males, aged from 4 to 70 years old, with a median of 53 years. For the repair, autologous materials such as free turbinate flap, free nasoseptal flap, pedicled nasoseptal flap, and fascia lata combined with mashed muscle were used. Initial reconstruction was successful in 26 cases, while 5 patients required a second repair, which was also successful. Postoperatively CNS infections occurred in 4 patients, and all of whom were cured. Follow-up ranged from 3 to 146 months, with no delayed CSF leak reported. The infection rate was significantly higher in patients whose first repair failed compared to those whose repair was successful (Fisher exact test, P<0.001). Conclusions:The use of different autologous materials based on the patient′s condition can effectively repair CSF leakage that occurs during EECR. Howerver, the success rate of initial repair requires improvement, as the risk of CNS infection significantly increases after a failed repair..

Radical cystectomy combined with pelvic lymph node dissection is the standard procedure for the treatment of muscle invasive bladder cancer and complex non-muscle invasive bladder cancer.Our department has routinely carried out laparoscopic radical cystectomy(ELRC)through the extraperitoneal approach in 340 cases.This article summarizes the establishment of the peritoneal space,the expansion of the peritoneal space,the operation steps of bladder resection and lymph node dissection through the peritoneal channel,and how to shorten the operation time and reduce the difficulty of the operation.During the surgery,the bladder is removed periperitoneally without destroying the peritoneum to preserve the functions of peritoneum support,secretion,protection and lubrication,which has little impact on the abdominal organs,reduces the incidence of complications,and provides favorable conditions for subsequent treatment.

Objective:To discuss the ameliorative effect of a novel antiepileptic drug Q808 on neuronal injury in temporal lobe epilepsy(TLE)rats,and to clarify its mechanism of action.Methods:TLE rat model was prepared by intraperitoneal injection of the innovative antiepileptic drug candidate 6-(4-chlorophenoxy)-tetrazolo(5,1-a)phthalazine(Q808).Forty-five successfully modeled rats were randomly divided into model group,low dose of Q808 group,and high dose of Q808 group,and there were 15 rats in each group.The rats in low dose of Q808 group and high dose of Q808 group were gavaged with 20 and 80 mg·kg-1 Q808,respectively,and the rats in model group were gavaged with an equal amount of 0.3％sodium carboxymethyl cellulose.Another 15 healthy SD rats were selected as control group.After 4 weeks of continuous gavage treatment,the morphology of the rats in varioius groups was observed;PONEMAH 6.X experimental animal telemetry platform was used to record the electroencephalogram of the rats in various groups;Golgi staining was used to observe the morphology of dendritic and dendritic spine density of hippocampal CA1 neurons of the rats in various groups;Western blotting method was used to detect the expression levels of synaptic plasticity-specific protein calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)in hippocampus tissue of the rats in various groups.Results:The rats in control group showed normal activity without convulsions or other abnormal manifestations.The rats in model group,low dose of Q808 group,and high dose of Q808 group showed varying degrees of reduced activity,trembling and nodding,loss of balance,muscle rigidity and forelimb convulsions,gradually transforming into whole-body muscle rigidity and standing,followed by falling backwards,and there were no convulsions during the interictal period.Compared with control group,the total durations of epileptic seizures of the rats in model group,low dose of Q808 group,and high dose of Q808 group were significantly prolonged(P＜0.01).Compared with model group,the total durations of epileptic seizures in low dose of Q808 group and high dose of Q808 group were significantly shortened(P＜0.01).The hippocampal CA1 neurons of the rats in control group showed regular distribution of dendrites with dense and orderly dendritic networks.The hippocampal CA1 neurons of the rats in model group showed disordered arrangement of dendrites with massive dendritic entanglement,forming thicker nerve fiber bundles.Compared with model group,the dendritic networks of hippocampal CA1 neurons of the rats in low dose of Q808 group and high dose of Q808 group were partially recovered with relatively regular arrangement.Compared with control group,the dendritic spine density of hippocampal CA1 neurons of the rats in model group was significantly decreased(P＜0.01).Compared with model group,the dendritic spine densities of hippocampal CA1 neurons in low dose of Q808 group and high dose of Q808 group significantly increased(P＜0.01).Compared with control group,the expression levels of CaMKⅡ protein in hippocampus tissue of the rats in model group,low dose of Q808 group,and high dose of Q808 group were significantly decreased(P＜0.01).Compared with model group,the expression levels of CaMKⅡ protein in hippocampus tissue of the rats in low dose of Q808 group and high dose of Q808 group were significantly increased(P＜0.01).Conclusion:The novel antiepileptic drug Q808 has an ameliorating effect on the TLE model rats;its mechanism may be related to Q808's ability to reduce the dendritic lesions in hippocampal CA1 neurons and increase the expression level of synaptic plasticity-related protein CaMKⅡ protein.

Objective To investigate the application value of the fluorescence quantitative PCR(qPCR)melting curve method in the detection of clarithromycin(23S rRNA)and quinolone(gyrA)resistant genes of Helicobacter pylori(Hp)in fecal samples.Methods A total of 1 176 untreated patients who underwent gastroscopy and were Hp positive proved by rapid urease test(RUT)were enrolled in the study.Their gastric mucosal and fecal samples were collected.The E-test method was used to analyze the clarithromycin and quinolone resistant phenotypes of Hp in gastric mucosal samples.The qPCR melting curve method was used to detect the clarithromycin and quinolone resistant genotypes of Hp in fecal samples.The consistency of the results obtained by the two methods was evaluated by the Kappa test.In addition,the nucleic acids were extracted from the fecal samples with Hp positive,and the Hp 23S rRNA and gyrA resistance mutation genes were detected by the qPCR melting curve method and Sanger sequencing,respectively.The consistency of the results obtained by the two methods was compared.Results In the study of clarithromycin resistance,a total of 934 valid samples were obtained.Among them,453 samples had positive resistance phenotype and 481 had positive resistance genotype,with a positive consis-tency rate of 93.38%(95%CI:90.70%～95.32%).In the study of quinolone resistance,a total of 909 valid samples were obtained.Among them,426 samples had positive resistance phenotype and 413 had positive resistance genotype,with a positive consistency rate of 86.85%(95%CI:83.31%-89.74%).In the comparative study,986 valid samples were detected for Hp 23S rRNA gene.Among them,514 samples were resistance positive detected by the qPCR melting curve method and 509 by Sanger sequencing,with a positive consistency rate of 96.27%(95%CI:94.24%-97.60%).Similarly,895 valid samples were detected for Hp gyrA gene.Among them,422 samples were resistance positive detected by the qPCR melting curve method and 405 by Sanger sequencing,with a positive consis-tency rate of 95.80%(95%CI:93.38%-97.36%).Conclusion The qPCR melting curve method can detect Hp 23S rRNA and gyrA in fecal samples,which has certain clinical application value for predicting the resistance of Hp.

Objective:To study the prevalence of skeletal fluorosis in drinking-water-borne endemic fluorosis areas in Inner Mongolia Autonomous Region (Inner Mongolia), and to provide reference for further prevention and treatment of skeletal fluorosis at this stage.Methods:From March to October 2019, a survey of skeletal fluorosis was carried out in all diseased villages of the eight diseased leagues (cities) in Inner Mongolia, including Alxa, Bayannur, Baotou, Ordos, Hohhot, Hulunbeier, Ulanqab and Xilingol. Permanent residents aged 18 years and above in the diseased villeges were investigated. Face to face questionnaires were used to collect the basic data of age, sex, epidemiological history, etc. of all subjects, and clinical examination of skeletal fluorosis was carried out. Drinking water samples were collected from residents for fluoride content testing.Results:A total of 123 166 residents aged 18 years and above were investigated, 1 781 cases of skeletal fluorosis were detected, and the detection rate was 1.45%. The degree of skeletal fluorosis was mild, accounting for 72.26% (1 287/1 781); the others were moderate and severe, accounting for 20.38% (363/1 781) and 7.36% (131/1 781), respectively. There were statistically significant differences in the detection rates of skeletal fluorosis among people of different water fluoride content, age, gender and regions (χ 2 = 565.96, 671.32, 4.38, 17 283.80, P < 0.05). Among them, the detection rates of skeletal fluorosis in water fluoride content > 4.0 mg/L, ≥56 years old and female population were relatively high, which were 5.21% (49/941), 2.26% (1 428/63 188) and 1.52% (905/59 555), respectively. The detection rates of skeletal fluorosis in Xilingol League and Baotou City were significantly higher, 25.48% (745/2 924) and 24.32% (225/925), respectively. Conclusion:The situation of skeletal fluorosis in drinking-water-borne endemic fluorosis areas in Inner Mongolia has been effectively controlled, but there are still relatively many patients with skeletal fluorosis in some areas, and further targeted prevention and control work is needed.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.