Objective To investigate the correlation of hs-CRP and systemic immunoinflammatory index(SII)with the severity of coronary artery stenosis in elderly T2DM patients.Methods A retrospective trial was conducted on 158 elderly T2DM patients admitted to the Affiliated Hospi-tal of Xuzhou Medical University from August 2021 to August 2023.According to the results of coronary angiography,they were divided into mild(Gensini score≤60,79 cases)and severe steno-sis groups(＞60,79 cases).Spearman correlation analysis and logistic regression analysis were ap-plied to analyze the correlation and the risk factors for severe stenosis.Results Significantly high-er hs-CRP and SII were observed in the severe stenosis group than the mild stenosis group(P＜0.01).Hs-CRP,SII,glycosylated hemoglobin,neutrophils,hsTNT,NLR,and PLR were positively correlated with Gensini score(r=0.424,P＜0.01;r=0.367,P＜0.01;r=0.207,P＜0.01;r=0.259,P＜0.01;r=0.187,P＜0.05;r=0.317,P＜0.01;r=0.256,P＜0.01),and the course of T2DM was negatively correlated with Gensini score(r=-0.224,P＜0.01).Multivariate logistic regression showed that hs-CRP and SII were independent risk factors for severity coronary artery stenosis in elderly T2DM patients(OR=3.191,95％CI:1.847-5.513,P=0.000;OR=1.006,95％CI:1.004-1.009,P=0.000).Conclusion Elderly T2DM patients have higher levels of hs-CRP and SII,which may be independent risk factors for the pathogenesis of coronary stenosis.

Abstract: Objective　To analyze the distribution characteristics of the main pathogens of HIV/AIDS patients with wound infections and provide basis for clinical diagnosis and treatment. Methods　The clinical data of 294 patients with positive secretions or pus specimens from 2016 to 2020 were analyzed retrospectively. Results　A total of 357 strains of pathogenic bacteria were isolated from 294 cases, of which 123 strains of Gram-negative bacilli (G-b), accounting for 34.5%, were mainly Escherichia coli (15.4%), Klebsiella pneumoniae (3.9%), and Pseudomonas aeruginosa (3.6%); Gram-positive bacilli (G+b) 14 strains, accounting for 3.9%; 108 Gram-positive cocci (G+c), accounting for 30.3%, of which 44 strains were coagulase-positive Staphylococcus aureus (12.3%), Coagulase-negative staphylococci were mainly Staphylococcus epidermidis (4.2%) and Staphylococcus hemolyticus (2.8%); 37 strains of fungi, accounting for 10.4%, were mainly Candida albicans (5.9%); 75 strains of Mycobacterium, accounting for 21.0%, including 41 strains of Mycobacterium tuberculosis (11.5%) and 34 strains of non-tuberculosis mycobacteria (9.5%). 52 of the 294 HIV/AIDS patients had mixed infections, accounting for 17.7%. There was significant difference in the distribution of G+c, G-b, mycobacteria and mixed infection among different specimen sources (P<0.05), and there was significant difference in the distribution of mycobacteria among different CD4+T lymphocyte counts (P<0.05). There was significant difference in the level of CD4+T lymphocytes between patients of different ages (P<0.05), and there was significant difference in the level of CD4+T lymphocytes from postoperative incision and other parts (P<0.05). Conclusions　Patients with HIV/AIDS are prone to combined wound infections with various pathogenic bacteria. We should strengthen the research on wound infection in HIV/AIDS patients, and timely send patients with a low number of CD4+T lymphocytes for secretion or pus culture, so as to carry out targeted treatment and improve the prognosis of patients.

OBJECTIVE: To explore the genetic basis for a rare case with Disorder of sex development. METHODS: Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out. RESULTS: The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46,XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47,XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient's karyotype was ultimately determined as 46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223). CONCLUSION The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.
Female ; Humans ; Adolescent ; DNA Copy Number Variations ; In Situ Hybridization, Fluorescence ; Y Chromosome ; Sexual Development ; Mosaicism

As the National Health Commission changes the management of novel corona virus infection, the situation and preventive policies for controlling the epidemic have also entered a new stage in China. Perioperative care strategies for orthopedic trauma such as designated isolation and nucleic acid test screening have also been adjusted in the new stage. Based on the perioperative work experiences in the new stage of epidemic from the frontline anti-epidemic staff of orthopedics in domestic hospitals and combined with the literature and relevant evidence-based medical data in perioperative care of orthopedic trauma patients under the current anti-epidemic policies at home and abroad, Chinese Orthopedic Association and Chinese Society of Traumatology organized relevant experts to formulate the Guideline for clinical perioperative care of orthopedic trauma patients in the new stage of novel corona virus infection ( version 2023). The guideline summarized 16 recommendations from the aspects of preoperative diagnosis and treatment, infection prevention, emergency operation and postoperative management to systematically standardize the perioperative clinical pathways, diagnosis and treatment processes of orthopedic trauma in the new stage of novel corona virus infection, so as to provide a guidance and reference for hospitals at all levels to carry out relevant work in current epidemic control policies.

Purpose: To report a case of orbital infarction syndrome in a patient with hemophagocytic lymphohistiocytosis (HLH).Case summary: A 70-year-old woman with diabetes mellitus and hypertension was referred to the Department of Ophthalmology for sudden-onset left upper eyelid ptosis after being diagnosed with HLH. After 3 days, the best corrected visual acuity in the right eye was 0.8, while there was no light perception in the left eye. In the left eye, the ocular motility examination showed limitations in all fields of gaze. On fundus examination, optic disc pallor, retinal hemorrhage, and narrowed retinal arteries were observed in the left eye. Fluorescein angiography showed no blood flow in the retinal arteries and veins in the left eye. On neck computed tomography angiography, the left distal internal carotid artery was narrowed. Orbit computed tomography showed exophthalmos and extraocular muscle hypertrophy in the left eye. Orbit magnetic resonance imaging confirmed optic nerve edema, enhancement of the optic nerve sheath, and high signal intensity of the intraocular fat in the left eye. Slit-lamp examination revealed ischemia of the anterior segment and ischemic necrosis of the eyelid in the left eye. The patient was diagnosed with orbital infarction syndrome. Conclusions Several factors may lead to ischemia of the orbital tissues in patients with HLH, including coagulopathy, an increased incidence of blood clots, and inflammation in the orbit. It is necessary to consider the possibility of orbital infarction syndrome when HLH patients present with visual loss, ocular movement limitations, and anterior segment ischemia.

Objective:To investigate the role of hydrogen-rich salt water in improving depression-like symptoms and its possible molecular mechanism in rats.Methods:The experiment was divided into two stages. In the first stage, 35 healthy male SD rats were randomly divided into control group, model group, high-dose group, medium-dose group, and low-dose group ( n=7); rats in the control group and model group were gavaged with 8 mL/kg normal saline per d, and rats in the high-dose group, medium-dose group, and low-dose group were fed with 8 mL/kg hydrogen-rich saline water (containing 2, 1, and 0.5 ppm hydrogen) per d; except for the control group, the other groups were depressed with chronic unpredictable mild stimulation (CUMS) for 4 weeks. In the second stage, 30 healthy male SD rats were randomly divided into hydrogen water group, hydrogen water+fluoxetine group, and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition group ( n=10); optimal hydrogen concentration (0.8 ppm) hydrogen-rich saline water (8 mL/kg) per d was given to rats of these 3 groups by gavage; fluoxetine (5 mg/kg) by gavage was given to the hydrogen-water+fluoxetine group, and all-transretinoic acid (10 mg/kg) by gavage was given to the Nrf2 inhibition group; CUMS was given for 4 weeks in these 3 groups. Rats were weighed at fixed times at each weekend. Four weeks after intervention, the total distance and average speed of rats in each group were determined by open field test. After open field test, blood was collected from the orbital veins from all rats; serum superoxidase dismutase (SOD) and malondialdehyde (MDA) contents were determined by ELISA. The expressions of brain-derived neurotrophic factor (BDNF), heme oxygenase-1 (HO-1), Nrf2, and phosphorylated Nrf2 (p-Nrf2) in the hippocampal CA3 region were detected by Western blotting. Results:(1) In the first stage, after 3 and 4 weeks of intervention, as compared with the model group, the body weight of the rats in the high-dose group, medium-dose group, and low-dose group increased significantly ( P<0.05). As compared with the model group, the medium-dose group, and low-dose group had significantly increased total distance and average speed, significantly increased serum SOD content, significantly decreased serum MDA content, significantly increased BDNF and HO-1 expressions and decreased p-Nrf2 expression in the CA3 region of the hippocampus ( P<0.05). (2) In the second stage, after 3 and 4 weeks of intervention, as compared with the Nrf2 inhibition group, the body weight of the hydrogen water group and hydrogen water+fluoxetine group increased significantly ( P<0.05). As compared with the Nrf2 inhibition group, the hydrogen water group and hydrogen water+fluoxetine group had significantly increased total distance and average speed, significantly increased serum SOD content, significantly decreased serum MDA content, statistically increased BNDF and HO-1 expressions in the CA3 region of the hippocampus, and the hydrogen water+fluoxetine group had significantly increased Nrf2 and p-Nrf2 expressions in the CA3 region of the hippocampus ( P<0.05). As compared with the hydrogen water group, the hydrogen water+fluoxetine group had significantly increased BNDF and HO-1 expressions and increased p-Nrf2 expression in the CA3 region of the hippocampus ( P<0.05). Conclusion:Hydrogen-rich salt water can increase the serum SOD and reduce the serum MDA, increase the BDNF and HO-1 protein expressions in the hippocampal areas of depressed rats, thereby improving the depression-like symptoms; the synergistic effect of hydrogen-rich saline water and fluoxetine on anti-depression may be related to antioxidant effect of Nrf2 signaling.

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.

Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C18 col-umn(4.6 mm×50 mm,5 μm)under gradient conditions with eluents of methanol:acetonitrile(1∶1,V/V)and 5mM ammonium formate:methanol(9∶1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30 → 437.30 for RA and m/z 256.10 → 227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40 mg/kg)and intravenous(10 mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20 mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1％to 19.4％.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*