BACKGROUND:Currently,there is a lack of large sample studies to analyze the bone metabolism level of patients with femoral head necrosis of different etiologies and stages,which is not conducive to the development of better necrosis-promoting repair strategies. OBJECTIVE:To study the bone metabolism of patients with osteonecrosis of the femoral head with different etiologies and Association Research Circulation Osseous(ARCO)stages. METHODS:A retrospective study was performed on 401 patients diagnosed with osteonecrosis of the femoral head as the trial group,and 81 healthy subjects as the control group.The trial group could be divided into three groups according to different etiologies:steroid-induced osteonecrosis of the femoral head,alcoholic osteonecrosis of the femoral head and traumatic osteonecrosis of the femoral head,and were divided into stages Ⅱ/Ⅲ/Ⅳ according to different ARCO stages.Seven bone metabolism-related indicators of all subjects were collected,including bone metabolism-regulating hormone 25-hydroxyvitamin D and bone conversion markers:N-terminal propeptide of type Ⅰ procollagen,degradation product of type Ⅰ collagen,n-terminal middle molecular fragment of osteocalcin,general biochemical markers of bone metabolism:serum calcium,serum phosphorus,serum alkaline phosphatase.The bone metabolism levels of each group were compared and the independent factors associated with osteonecrosis of the femoral head were determined by binary Logistic regression analysis. RESULTS AND CONCLUSION:Compared with the control group,levels of degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,n-terminal middle molecular fragment of osteocalcin,serum phosphorus and alkaline phosphatase in the trial group were significantly increased(all P＜0.05).Based on the presence or absence of the disease,according to binary Logistic regression analysis,degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,and n-terminal middle molecular fragment of osteocalcin were independent factors associated with osteonecrosis of the femoral head.The levels of degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in three groups of patients with different etiologies were higher than normal reference values.The bone metabolism-regulating hormone 25-hydroxyvitamin D and serum calcium in the alcoholic osteonecrosis of the femoral head group were higher than those in the other two groups(P＜0.05).The level of bone metabolism-regulating hormone 25-hydroxyvitamin D in steroid-induced and traumatic osteonecrosis of the femoral head groups was lower than the normal value.There were no significant differences in seven bone metabolism-related indicators in patients with ARCO stages Ⅱ,Ⅲ and Ⅳ osteonecrosis of the femoral head(all P＞0.05),but degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in these three groups were higher than normal reference values.Bone metabolism-regulating hormone 25-hydroxyvitamin D in patients with ARCO stage Ⅱ and ARCO stage Ⅳ was lower than the normal reference value.It is concluded that the bone metabolism level of osteonecrosis of the femoral head patients was abnormal.The degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen of osteonecrosis of the femoral head patients with different etiologies and ARCO stages were all higher than the normal reference value,and they were in a state of high bone turnover.Degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen and n-terminal middle molecular fragment of osteocalcin may be risk factors for the pathogenesis of osteonecrosis of the femoral head.

Objective To analyze the correlation between the comorbidity of chronic diseases and concurrent traditional Chinese medicine(TCM)constitutions in the elderly in Guangzhou.Methods From the physical examination data of 3 communities in Guangzhou,3 078 elderly people were selected as the survey objects,and association analysis was performed for mining the association rules between the chronic disease comorbidity and concurrent TCM constitution types of the elderly with different demographic characteristics.Results The comorbidity rate of chronic diseases in the elderly of Guangzhou area was 76.54％(2 356/3 078).In the elderly population of Guangzhou area,the correlation of chronic disease comorbidity with the concurrent constitution of tendentious blood stasis constitution and phlegm-damp constitution had the highest confidence,which was 95.87％.The correlation of chronic disease comorbidity with the gender showed that the concurrent constitution was similar in the elderly with different genders.The correlation of chronic disease comorbidity with the concurrent constitution of phlegm-damp constitution and tendentious yin deficiency constitution in the male elderly had the confidence of 94.38％,and the correlation of chronic disease comorbidity with the concurrent constitution of phlegm-damp constitution and tendentious blood stasis constitution in the female elderly had the confidence of 97.46％.With the increase of the age,the biased constitution of the elderly with chronic diseases gradually developed into the concurrent constitution of phlegm blended with blood stasis,and the concurrent constitution of qi deficiency constitution and yang deficiency constitution became the predominated.Conclusion The comorbidity rate of chronic diseases in the elderly is high.The association patterns of the comorbidity of chronic diseases with concurrent constitution types vary in different age groups.Medical institutions can condition the concurrent constitution with Chinese medicine therapy according to the characteristics of the concurrent constitutions of the elderly,and then can improve the comorbidity of chronic diseases in the elderly.

An increasing number of studies have been focused on the field of immune system in the central nervous system(CNS),as the viewpoint of CNS immune privilege being challenged.Among them,CNS boarder-associated macrophages(BAMs)play a prominent role in the regulation of brain homeostasis and related diseases.Unlike microglia located in the brain parenchyma,BAMs are a type of specialized macrophages located in the meninges(including dura,arachnoid,and leptomeninges),perivascular spaces,and choroid plexus.They are crucial for immune surveillance,cerebrospinal fluid drainage,antigen clearance,material exchange,and etc.Here,we reviewed a series of relevant studies on the origin and roles of BAMs in CNS,so as to broaden the understanding of the mechanisms of by which BAMs maintain the brain homeostasis,as well as provide novel insights into the treatment of CNS diseases including Alzheimer's disease.

Objective:This study aims to evaluate the performance of digital PCR (dPCR) detecting multiple and single copies genes of the Epstein-Barr virus (EBV) for nucleic acid quantification and explore their applicability in clinical settings.Methods:Compared the sensitivity, specificity, precision, lower limit of detection (LoD), and linearity for multicopy BamHI-W dPCR and single-copy EBNA1 dPCR systems. Linear regression analysis using the least squares method was employed to evaluate the linearity. Additionally, we analyzed plasma samples from 182 patients with suspected EBV-related diseases between January and July 2022 at the Southern Medical University Southern Hospital, using both dPCR and quantitative PCR (qPCR) for EBV DNA quantification. Linear regression analysis using the least squares method was conducted to assess their quantitative correlation.Results:The dPCR systems for both multicopy and single-copy genes showed excellent linearity ( R 2 values of 0.992 and 0.997, respectively, both P<0.001). The LoD were 188 IU/ml for BamHI-W gene and 358 IU/ml for EBNA1 gene dPCR systems. The logarithmic coefficient of variation ( CV) values for high-concentration samples (1 000 000 IU/ml) were 0.34% and 0.21% for the BamHI-W gene and EBNA1 gene dPCR assays, respectively, while for low-concentration samples (5 000 IU/ml) were 0.98% and 0.64%, respectively. In the detection of seven common clinical infectious pathogens and EBV positive samples, only EBV-positive samples yielded positive signals in the dPCR detection system, with no cross-reaction with other pathogens. In 182 samples, the positive detection rates were 47.80% (87/182) for BamHI-W gene and 35.16% (64/182) for EBNA1 gene dPCR, compared to 43.41% (79/182) for qPCR. Linear correlation analysis with qPCR showed R2 values of 0.837 for BamHI-W gene and 0.763 for EBNA1 gene dPCR (both P<0.001). The BamHI-W gene copy number ranged from 3 to 18 copies per clinical sample, with patient-specific variations. There was a high consistency in viral load trends between the multicopy BamHI-W gene and single-copy EBNA1 gene dPCR systems within individual patients. Conclusions:The dPCR methods detecting EBV multiple and single copies genes showed high sensitivity, specificity, precision, and quantitative accuracy, suitable for clinical sample analysis. The multicopy BamHI-W gene dPCR method notably enhances detection sensitivity and can be used as a supplement to current EBV DNA load detection methods, especially in low-concentration samples. For within-patient EBV DNA monitoring, the multicopy gene method proves more effective, while inter-patient comparisons might necessitate single-copy gene methods or normalize them using the same standard.

Background/Aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China. Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected. Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap. Conclusions FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
Adult ; Humans ; Immunity, Humoral ; Coinfection ; Interleukin-4 ; Interleukin-5 ; Immunoglobulin G ; Interferon-gamma

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
Adult ; Humans ; Immunity, Humoral ; Coinfection ; Interleukin-4 ; Interleukin-5 ; Immunoglobulin G ; Interferon-gamma

Objective To evaluate the value of chromosomal microarray analysis (CMA) for genetic evaluation of fetal ultrasound abnormality. Methods A total of 180 pregnant women with fetal abnormality detected by prenatal ultrasound diagnosis in the first trimester during the period from January 2020 through May 2022 were enrolled as the study subjects. All prenatal fetal screening samples were subjected to G-band karyotyping and CMA. Results G-band karyotyping detected normal karyotypes in 168 samples (93.85%) and abnormal karyotypes in 11 samples (6.15%), and CMA detected 17 positive samples (9.44%) and 163 negative samples (90.56%). The seventeen positive samples included 11 pathogenic copy number variations (CNVs) and 6 variants of unknown significance (VOUS), and there were 11 CMA-positive results consistent with G-band karyotyping, and 6 additional pathogenic CNVs mainly included microdeletion and microduplication syndromes. The detection rates of pathogenic CNVs were 11.11%, 2.63%, 2.78%, 4.00%, 0, 0, 11.11% and 0 among the fetuses with abnormal structure of the cardiovascular system, the lymphatic system, the nervous system, the digestive system, the cranial and face system, the skeletal system, the urinary system, and other system (χ² =8.188, P = 0.316). All eleven fetuses with pathogenic CNVs detected by CMA were all induced for abortion. Conclusion CMA improves the detection of genetic abnormality among fetuses with ultrasound abnormality in relative to G-band karyotyping, which is feasible for prenatal cytogenetic diagnosis among fetuses with ultrasound abnormality

OBJECTIVE: To investigate the effect of a noval radio-frequency atmospheric-pressure glow discharge (RF-APGD) plasma jet on crosslinking of dentin collagen. METHODS: (1) Twenty intact third molars were collected. The middle dentin discs were prepared for each tooth by low-speed water-cooled Isomet saw, and then immersed in 10% (mass fraction) H₃PO₄ solution for 16 h to obtain fully demine-ralized dentin collagen. The twenty dentin discs were then randomly divided into five groups. The control group was untreated while the four experimental groups were treated by plasma jet with gas temperature of 4 ℃ for different times (20 s, 30 s, 40 s, and 50 s). The structure and crosslinking degree of dentin collagen were characterized by attenuated total reflection-Fourier transform infrared spectroscopy. The surface morphology of demineralized dentin was observed by scanning electron microscope, and the microstructure was observed by transmission electron microscope. (2) Fourty non-caries third molars were collected to prepare 5 g fine dentin powder, then completely demineralized with 10% H₃PO₄ solution. The control group was untreated, while the four experimental groups were treated by plasma jet for 20 s, 30 s, 40 s and 50 s. The crosslinking degree of each group was determined by ninhydrin colorimetric method. (3) Forty intact third molars were collected to obtain dentin strips. Only two central symmetrical dentin strips (nasty 80) were taken from each tooth and immersed in 10% H₃PO₄ solution for 16 h to obtain fully demineralized dentin collagen. Eighty dentine collagen fiber strips were randomly divided into five groups. The control group was untreated and the axial surfaces of dentin collagen fiber strips in the expe-rimental groups were treated with the plasma jet for 20 s, 30 s, 40 s and 50 s. The ultimate tensile strength of dentin was measured by universal mechanical machine. RESULTS: (1) The surface morphology of demineralized dentin observed by scanning electron microscope showed that the network structure of collagen fibers on the surface of demineralized dentin treated with the plasma jet for 20 s, 30 s and 40 s could maintain the uncollapsed three-dimensional structure, and part of the microstructure was destroyed after plasma jet treated for 50 s. After being treated by plasma jet for 20 s, 30 s and 40 s, the three-dimensional structure was uncollapsed, and the typical periodic transverse pattern of natural type Ⅰ collagen fiber could be seen. The results of infrared spectra showed that the secondary conformation of dentin collagen fibers was the same as that of the control group after being treated with the plasma jet, and the intensity of amide band was significantly increased after being treated for 30 s and 40 s. (2) The results of ninhydrin crosslinking test showed that the crosslinking ratio of dentin collagen treated by plasma jet for 30 s and 40 s was the highest, and the difference was statistically significant (P < 0.05). (3) The results of dentin ultimate tensile strength showed that the control group was (1.67±0.24) MPa, and the plasma jet treated 20 s, 30 s, 40 s and 50 s groups were (4.21±0.15) MPa, (7.06±0.30) MPa, (7.32±0.27) MPa, and (6.87±0.17) MPa, which were significantly different from that of the control group (P < 0.05). CONCLUSION The novel RF-APGD plasma jet treatment can promote the crosslinking degree of demineralized dentin collagen and improve their ultimate tensile strength.
Collagen ; Dental Bonding ; Dentin ; Dentin-Bonding Agents ; Microscopy, Electron, Scanning ; Tensile Strength