PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective:To provide a basis for improving the design and implementation of policies for ensuring the supply of pediatric drugs in China.Method:Based on the perspective of pharmaceutical enterprises,reviewed literature and conducts questionnaire surveys to identify the constraints in the development of pediatrict drugs throughout the entire drug lifecycle,and analyzes the constraints'concentration and urgency.Result:The main constraints include:difficulty in conducting clinical trials for children;the current registration and approval rules lack consideration for the specificity of pediatric drugs and specific requirements for application materials;lack of implementation rules and measures in the implementation process of incentive policies for pediatric drug production;The market interest mechanism of pediatric drugs is not yet perfect.Among them,research and development and payment for use are currently relatively concentrated issues.Discussion and suggestions:It is recommended that China fully utilize existing clinical trial data of pediatric and broaden sources,take multiple measures to increase investment in pediatric drug R&D;Develop special guidelines for pediatric drug application and encourage adult drug registration to submit pediatric research plans;Explore the optimization path of pediatrict drug production and supply based on typical cases;Provide more space for pediatric drugs in the rules of drug use and payment.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: To investigate clinical efficacy and safety of single and double segmental percutaneous lumbar discectomy for young and middle-aged patients with double-segment disc herniation. METHODS: Retrospective analysis was undertaken for 32 young and middle-aged patients with percutaneous endoscopic lumbar discectomy (PELD) in the treatment of double-segment lumbar disc herniation from January 2015 to October 2018 in Peking University First Hospital. In the study, 18 cases were treated with single-segment treatment and 14 cases with double-segment treatment. Visual analogue score (VAS) and oswestry disability index (ODI) assessment were used to compare clinical symptom outcomes before surgery, 3 months after surgery and at the last follow-up. Macnab criteria were used to assess the patients' overall satisfaction after surgery. Imaging parameters included lumbar lordosis, intervertebral height at each segment and endplate angle of lesion segment on the X-ray. And Michigan State University(MSU) rating and Pfirrmann scoring system were used to evaluate the grade of disc herniation and disc degeneration respectively on magnetic resonance imaging (MRI). The perioperative parameters included the surgeon, anesthesia method, operation time, postoperative hospital stay, postoperative bracing time and perioperative complications. RESULTS: The mean follow-up time was (26.78±10.64) months. There was no significant difference in the follow-up time and baseline information between the two groups(P > 0.05). ODI scores 3 months post-operatively and at the last follow-up were lower in the double segment (P < 0.05). The ODI improvement was also more significant in the double-segment group at the last follow-up (P < 0.05). There was no significant difference in radiographic parameters at baseline (P>0.05). MSU scale for the primary segment was significantly lowered after both operations (P < 0.05). MSU scale for secondary segment was significantly lowered in double segment group but not in single segment group. Other imaging parameters were similar between the two groups (P > 0.05). The operation time of the single-segment group was significantly shorter than that of the double-segment group(P < 0.001). No perioperative complications were found in either group, but three patients underwent secondary lumbar surgery during the postoperative follow-up period in the single-segment group. CONCLUSION For young and middle-aged patients with double-segment disc herniation, this study suggests double-segment PELD may be more advantageous than single-segment PELD in terms of asuring clinical efficacy without increasing perioperative risks.
Diskectomy ; Diskectomy, Percutaneous ; Endoscopy ; Humans ; Intervertebral Disc Degeneration/surgery* ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Middle Aged ; Retrospective Studies ; Treatment Outcome

Professor
Acupuncture ; Acupuncture Therapy ; Angina, Stable ; Combined Modality Therapy ; Humans ; Moxibustion

Objective: To investigate the impact of iron deficiency (ID) on prognosis in heart failure patients with preserved ejection fraction (HFpEF). Methods: A total of 215 consecutive patients with HFpEF, who visited the cardiovascular outpatient department of Beijing Anzhen Hospital, were enrolled in this prospective study. The plasma ferritin level and transferin saturation were measured. Patients were divided into two groups: ID group and non-ID group. ID patients were further divided into absolute ID subgroup and functional ID subgroup. Patients were followed up to 1 year. The endpoints of the study were all-cause mortality and rehospitalization for heart failure (HF). The independent predictors of outcome were determined by Cox regression model. The quality of life of patients was evaluated at the end of the follow-up. Results: The age of this patient cohort was (67±8) years, 39.1% patients were male. The prevalence of ID was 54.4%. Within one year of follow-up, 37 patients (17.2%) died and 70 patients (32.6%) were rehospitalized for HF. Compared to non-ID group, patients in ID group were older, had higher heart rate, lower plasma hemoglobin level and estimated glomerular filtration rate (eGFR) value, had a higher prevalence of anemia and chronic kidney disease (P all<0.05). Kaplan-Meier curves showed that all-cause mortality and rehospitalization for HF in HFpEF patients with ID were higher than patients without ID, and prognosis was similar between patients with absolute ID and functional ID. Multivariable regression analysis showed that ID was an independent predictor for all-cause mortality and rehospitalization for HF in HFpEF patients. The of 6 minutes walking distance was shorter ((356.0±98.3)m vs. (389.2±94.3)m, P=0.023), and the value in Kansas city cardiomyopathy questionnaire was lower ((58.06±10.43) m vs. (61.51±11.64) m, P = 0.039) in patients with ID than patients without ID. Conclusion: In patients with chronic HFpEF, ID is an independent predictor for all-cause mortality and rehospitalization for HF at one year of follow-up, independent of the types of ID.
Aged ; Anemia, Iron-Deficiency ; Female ; Heart Failure/complications* ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Quality of Life ; Stroke Volume

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

OBJECTIVE: To evaluate the diagnostic value of ¹⁸F-FDG PET/CT and tumor markers (CEA,CA19-9,CA24-2) in detection for recurrence and metastasis of postoperative colorectal moderately differentiated adenocarcinoma. METHODS: Fifty-five patients were enrolled in this study. All of the patients were tested with serum CEA within 2 weeks when they underwent ¹⁸F-FDG PET/CT scan, and some patients were tested with serum CA19-9 and CA24-2 simultaneously. According to the pathology and clinical results of their follow-up, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ¹⁸F-FDG PET/CT and tumor markers were calculated based on different divided groups, respectively. RESULTS: According to the pathology and the results of their clinical follow-up, the sensitivity of ¹⁸F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 95.74%, 68.09%, 28.57%, 40.00% and 74.47%, respectively. The specificity of ¹⁸F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 75.00%, 50.00%, 66.67%, 71.43% and 50.00%, respectively. The positive predictive valueof ¹⁸F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 95.74%, 88.89%, 85.71%, 88.89% and 89.74%, respectively. The negative predictive value of ¹⁸F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 75.00%, 26.67%, 11.42%, 17.24%, 25.00%, respectively. The accuracy of ¹⁸F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 92.73%, 65.47%, 32.65%, 44.68% and 70.91%, respectively. There were 2 cases of false positive and 2 cases of false negative in ¹⁸F-FDG PET/CT. CONCLUSION ¹⁸F-FDG PET/CT has high value in detecting recurrence and metastasis of postoperative colorectal carcinoma. Tumor markers have the positive value to imply the recurrence and metastasis of postoperative colorectal carcinoma and are useful to indicate when to perform the ¹⁸F-FDG PET/CT. The combination of tumor markers could improve the diagnostic efficiency to some extent.
Adenocarcinoma/diagnosis* ; Biomarkers, Tumor ; CA-19-9 Antigen ; Carcinoembryonic Antigen ; Colorectal Neoplasms/diagnosis* ; Fluorodeoxyglucose F18 ; Humans ; Neoplasm Recurrence, Local ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Recurrence