Han Chinese Patients Research Articles

Identification of Two Novel Missense Variants in BNC1 in Han Chinese Patients With Non-syndromic Premature Ovarian Insufficiency.

Two novel heterozygous missense mutations in BNC1 (NM_001717): c.1000A>G (p.Arg334Gly) and c.1535C>T (p.Pro512Leu) were identified through whole-exome sequencing in two Han Chinese POI patients, expanding the spectrum of BNC1 variants in non-syndromic POI diseases.

EDNRA affects susceptibility to large artery atherosclerosis stroke through potential inflammatory pathway

This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p < 0.001) and IL-18 concentrations (r = 0.212, p < 0.001). EDNRA is linked to susceptibility of LAA. This association may be attributed to the NLRP3-mediated inflammatory pathway.

Comparative analysis of myoelectric activity and mandibular movement in healthy and nonpainful articular temporomandibular disorder subjects.

Temporomandibular disorders (TMDs) are one of the leading causes of craniofacial pain, and a high incidence of TMDs in young adults has been reported. Previous studies have used surface electromyography (sEMG) and mandibular kinematic analysis for TMDs diagnosis. This study aimed to provide normal reference values of sEMG and mandibular kinematics in Han Chinese adults, compare the sex differences and assess their diagnosis value on pain-free articular TMDs. This observational study recruited healthy young adults with individual normal occlusion and nonpainful articular TMDs patients with disc displacement. The sEMG signals of the anterior temporalis (TA), masseter (MM), and sternocleidomastoid and digastric were recorded in the mandibular postural positions (MPP) and during maximal voluntary clenching (MVC) with K7 electromyograph. Mandibular kinematics, including maximum opening and opening/closing velocities, were assessed by K7 kinesiograph. The sEMG reference values ranged from 3.0 to 4.3 µV in the MPP (n = 90) in healthy subjects. The sEMG values during MVC, maximum opening, and opening velocity were significantly higher in males than in females. Also, these indices showed good diagnostic efficiency for pain-free articular TMDs (n = 26). Reference values and sex differences in sEMG and mandibular kinematics in healthy subjects were determined. Compared with them, articular TMDs patients showed significantly lower myoelectric activity during maximal biting and restricted mouth opening range and velocity, which may assist in TMDs diagnosis. By analyzing sEMG of masticatory muscle and mandibular kinematics data from healthy Han Chinese young adults and TMDs patients with disc displacement, this study evaluated the sex difference and their diagnosis value on nonpainful TMDs with disc displacement. NCT06372769.

Transcriptomic analysis of keratoconus in Han Chinese patients: Insights into differential gene expression and ethnic-specific patterns

Keratoconus (KC) is a progressive corneal ectatic disorder with a high prevalence among Asians. This study aimed to explore the differential gene expression patterns in Han Chinese patients with KC, focusing on mRNAs and long noncoding RNAs (lncRNAs), to provide insights into the pathogenesis of the disease.Corneal tissues from KC patients and healthy controls were collected, and RNA sequencing was performed to profile mRNA and lncRNA expression. A total of 1973 differentially expressed mRNAs (DEGs) and 386 differentially expressed lncRNAs (DELs) were identified in KC-affected corneas. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant enrichment in pathways related to ECM modulation, PI3K-Akt pathway and calcium signaling pathway. Furthermore, protein-protein interaction (PPI) network highlighted hub genes involved in ECM remodeling and inflammatory responses. Co-expression analysis of lncRNAs and mRNAs further prioritized 13 DELs linked to these hub genes. RT-qPCR validation confirmed the differential expression of select candidates. A meta-analysis integrating seven datasets from diverse ethnic backgrounds was performed and it suggested ethnic-specific differences in gene expression patterns.This study sheds new light on the molecular mechanisms underlying KC in the Han Chinese population, pinpointing potential therapeutic targets. It also emphasizes the critical role of ethnic-specific gene expression patterns in KC research, highlighting a need for tailored approaches in disease management and treatment.

Prevalence and risk factors of low bone mineral density in Chinese Han male patients with alcohol dependence.

To investigate the prevalence of low bone mineral density (BMD) along with its possible risk factors in male Han Chinese patients with alcohol dependence (AD). This retrospective, cross-sectional study included male patients with AD, classified into normal and low BMD groups according to bone densitometry T scores. Demographic and alcohol-related data, and routine laboratory parameters were compared between the two groups. Binary logistic regression analysis was employed to evaluate risk factors associated with low BMD, and correlations between the T-score and demographic, alcohol-related, and routine laboratory data were evaluated. Among a total of 107 patients with AD included in the study, the prevalence of low BMD was 70.09% (75/107). Patients with low BMD were older, consumed more alcohol daily, and had higher lactate dehydrogenase (LDH) and lower Ca2+ levels than patients with normal BMD. Regression analysis revealed that increased daily alcohol intake, low serum Ca2+ levels, high serum LDH levels, and comorbid hypertension was related to low BMD in patients with AD. Further correlation analysis revealed a positive association between T-score and serum Ca2+ levels. Increased daily alcohol intake, low serum Ca2+ levels, high serum LDH levels, and comorbid hypertension may be risk factors for low BMD.

The Association of HIF-1α/rs2057482 Polymorphism with Idiopathic Scleritis in a Chinese Han Population

ABSTRACT Background To investigate the association of hypoxia-inducible factor-1α (HIF-1α), Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) gene polymorphisms with idiopathic scleritis in a Chinese Han population. Methods Ten single nucleotide polymorphisms (SNP) of HIF-1α, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 3 (STAT3), signal transducer and activator of transcription 4 (STAT4), and retinoid-related orphan nuclear receptors-γ (ROR-γ) were selected for this study. A total of 496 idiopathic scleritis patients and 1009 controls were genotyped by the MassARRAY platform and iPLEX Gold Genotyping Assay. The allele and genotype frequencies were analyzed by Chi-square test and Fisher's exact test. Stratified analyses were performed based on gender and anatomic locations of idiopathic scleritis. Results The frequencies of CC genotype (p = 6.18 × 10−4, Pc = 0.04, OR = 0.67,95%CI = 0.53–0.84) and C allele (p = 7.08 × 10−4, Pc = 0.04, OR = 0.71,95%CI = 0.58–0.87) for HIF-1α/rs2057482 were found significantly lower in idiopathic scleritis patients when compared to healthy controls. Stratified analysis depending on gender showed significant decreased frequencies of CC genotype (CC: p = 4.04 × 10−4, Pc = 0.02, OR = 0.54, 95%CI = 0.39–0.76) and C allele (C: p = 1.62 × 10−4, Pc = 0.01, OR = 0.58, 95%CI = 0.44–0.77) in male patients. Stratification analysis of rs2057482 according to location of scleritis did not show any significant difference between three subgroups and healthy controls. Conclusion This study showed association between polymorphism of HIF-1α/rs2057482 and susceptibility to idiopathic scleritis in Han Chinese male patients.

The potential predictive value and relationship of blood-based inflammatory markers with the clinical symptoms of Han Chinese patients with first-episode adolescent-onset schizophrenia.

Inflammation is associated with the pathophysiology of schizophrenia. The blood markers for systemic inflammation include neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), lymphocyte-monocyte ratio (LMR), system inflammation response index (SIRI), and platelet-lymphocyte ratio (PLR). However, these inflammation markers and their relationships with clinical phenotypes among Han Chinese patients with first-episode adolescent-onset schizophrenia (AOS) is unclear. This investigation aimed to elucidate the impact of inflammation on Han Chinese AOS patients as well as the association of blood-based inflammation markers with clinical symptoms. Altogether, 203 Han Chinese individuals participated in this study, 102 first-episode AOS patients and 101 healthy controls. The assessment of inflammatory indices was based on complete blood cell count. Furthermore, schizophrenia-related clinical symptoms were evaluated using the five-factor model of the Positive and Negative Syndrome Scale (PANSS). In Han Chinese first-episode AOS patients, levels of SIRI, PLR, SII, and NLR were significantly increased (p < 0.001), while LMR decreased (p < 0.001) compared to healthy controls. Furthermore, multivariate logistic regression showed that LMR, NLR, SII, and SIRI (all p < 0.05) were independently associated with AOS. Moreover, Receiver operating characteristics assessment indicated that NLR, SIRI, LMR, and SII could effectively distinguish AOS patients from healthy controls. Their areas under the curves were 0.734, 0.701, 0.715, and 0.730 (all p < 0.001). In addition, Correlation analysis revealed that LMR was negatively correlated with the PANSS total, negative, and cognitive factor scores (all p < 0.05); NLR was positively correlated with the cognitive factor score (p < 0.01); SII was negatively correlated with the positive factor score and positively with the negative and cognitive factor scores (all p < 0.05); SIRI was positively correlated with the PANSS total and cognitive factor scores (all p < 0.01). This research established the involvement of peripheral blood inflammatory markers (LMR, NLR, SII, and SIRI) with the clinical manifestations and pathophysiology of schizophrenia, and these can serve as screening tools or potential indices of the inflammatory state and AOS symptoms severity.

A genome-wide methylation analysis of Chinese Han patients with chronic insomnia disorder.

As the most common sleep disorder, chronic insomnia disorder (CID) has become a global health burden to the public. However, it remains unclear about the pathogenesis of this disease. Epigenetic changes may provide important insights into the gene-environment interaction in CID. Therefore, this study was conducted to investigate the DNA methylation pattern in CID and reveal the epigenetic mechanism of this disease. In this study, whole blood DNA was extracted from 8 CID patients (the CID group) and 8 healthy controls (the control group), respectively. Besides, genome-wide DNA methylation was detected by Illumina Human Methylation 850K Beadchip. Moreover, the sleep quality and insomnia severity were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI), respectively. A total of 369 differentially methylated positions (DMPs) and 23 differentially methylated regions (DMRs) were identified between the CID and control groups. LHX6 was identified as the most important differentially methylated gene (DMG). The Gene Ontology (GO) analysis results corroborated that DMPs were significantly enriched in 105 GO terms, including cell signaling, homogenous cell adhesion of plasma membrane adhesion molecules, nervous system development, cell adhesion, and calcium ion binding. In addition, it was demonstrated that DMPs were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the hippo signaling pathway, Ras signaling pathway, and vitamin B6 metabolism. The DMR-related GO analysis results revealed the positive regulation of protein kinase activities. DNA methylation plays a critical role in the development of CID, and LHX6 is validated to be an important DMG.

Sex differences and risk factors of self-reported suicide attempts in middle-aged Chinese Han patients with first-episode drug-naïve anxious depression: a large-scale cross-sectional study.

This study aims to investigate sex differences and risk factors for self-reported suicide attempts among Chinese Han middle-aged patients with first-episode drug-naïve (FEDN) anxious depression (AD). A total of 1796 patients with FEDN major depressive disorder were enrolled in this study, including 341 middle-aged patients with AD. We compared the prevalence, demographics, and clinical characteristics of suicide attempts between male and female patients with FEDN middle-aged AD. We also explored the risk factors for self-reported suicide attempts in this population using binary logistic regression analysis. The male/female ratio was 91/250 and the age of onset was 51.50 ± 4.13. Our results showed that there were no significant sex differences in the prevalence of self-reported suicide attempts in middle-aged patients with FEDN AD. However, we did find significant differences in several demographic and clinical characteristics between self-reported suicide attempters and non-suicide attempters. Moreover, severe anxiety, measured by the Hamilton Anxiety Rating Scale score, was identified as a risk factor for self-reported suicide attempts in female middle-aged AD patients. Additionally, elevated thyroid peroxidase antibody (TPOAb) levels were linked to self-reported suicide attempts in male AD patients. Our findings suggest that there are no significant sex differences in the prevalence of self-reported suicide attempts in this population, but there may be sex-specific risk factors for self-reported suicide attempts in middle-aged AD. Clinical psychiatrists need to pay attention to thyroid hormone levels in middle-aged anxious depression.

Assessing the relationship of agger nasi pneumatization to the lacrimal sac: a dynamic computed tomography-dacryocystography analysis.

An understanding of the anatomical structure is crucial for completing successful endoscopic dacryocystorhinostomy (DCR) surgery. This study aimed to precisely delineate the spatial relationship between the lacrimal sac and the agger nasi cell (ANC) and evaluate the impact of ANC on surgical strategies in endoscopic DCR. This retrospective cross-sectional study included 110 Han Chinese patients diagnosed with unilateral primary acquired nasolacrimal duct obstruction (PANDO) from January 2021 to June 2023. This study was conducted in Eye, Ear, Nose, and Throat Hospital of Fudan University and involved inpatient participants who were scheduled for DCR surgery under general anesthesia. Patients were consecutively enrolled. The patients underwent preoperative computed tomography-dacryocystography (CT-DCG), and contrast-enhanced images were used to locate the positions of the lacrimal sac and the common canaliculus. A dynamic approach was adopted to analyze the multiplanar CT imaging, facilitating a detailed assessment of the morphology of the lacrimal drainage system and potential overlap of the lacrimal sac. Patient ages and measured values are presented as the mean ± standard deviation, which were measured three times by the same observer and averaged for statistical analysis. The prevalence of ANC in this study was 90.9% (100/110). Dynamic examination revealed that only 42.7% (47/110) of ANCs appeared as discrete cells, while the majority were connected to nearby sinus openings. Spatial analysis showed that in 57 out of 110 cases, ANCs were situated below the common canaliculus and not posterior to the lacrimal sac, indicating an overlap rate of 51.8%. Notably, our dynamic approach identified five critical cases of overlap below the level of the common canaliculus, which might have been missed by prior studies that used different methodologies. More than half of the ANCs exhibited overlap with the lacrimal sac, suggesting a significant proportion may necessitate opening during endoscopic DCR procedures. ANCs are often interconnected with adjacent nasal sinuses, necessitating careful consideration in the decision to open the ANCs during surgery. The dynamic evaluation employed in CT-DCG effectively assessed the extent of ANC coverage over the lacrimal sac.

Variants in PPARD-GLP1R are related to diabetic kidney disease in Chinese Han patients with type 2 diabetes mellitus

Genetic susceptibility is an important pathogenic mechanism in diabetic kidney disease (DKD). Our previous studies have identified that PPARδ and GLP-1R are located in a pathway that is closely related to DKD. We aimed to explore the impacts of variants in PPARD-GLP1R on the susceptibility to DKD in Chinese Han patients with type 2 diabetes mellitus (T2DM). A total of 600 T2DM patients (300 with DKD and 300 without DKD) and 200 healthy control subjects were enrolled to identify PPARD (rs2016520, rs2267668 and rs3777744) and GLP1R (rs3765467, rs1042044 and rs9296291) genotype. The SNaPshot method was used to identify variants in PPARD-GLP1R. We performed correlation analysis between variants in PPARD-GLP1R and the susceptibility to DKD. We observed that GLP1R rs3765467 (G > A) was associated with DKD (OR = 3.145, 95 % CI = 2.128–6.021, P = 0.035). None of the other SNPs were associated with DKD. Regarding DKD related traits, rs3765467 was associated with UACR levels and TC, significant differences were observed among patients with different genotypes of rs2016520 in terms of BMI and TG, and patients with the rs3777744 risk G allele had noticeably higher PPG and HbA1c levels (P < 0.05). Moreover, the results showed the interactions between PPARD rs3777744 and GLP1R rs3765467 in the occurrence of DKD (OR = 4.572, P = 0.029). The results of this study indicate the potential relationship between variants in PPARD-GLP1R and the susceptibility to DKD in Chinese Han patients with T2DM.

Generalized Joint Hypermobility Is Associated with Type-A Hip Dysplasia in Patients Undergoing Periacetabular Osteotomy.

Joint hypermobility may be associated with developmental dysplasia of the hip (DDH), but no definite conclusion has been reached. On the basis of long-term clinical observations, we hypothesized that joint hypermobility was associated with the occurrence, imaging findings, and clinical symptoms of DDH. We conducted a case-control study that included 175 Chinese Han patients between 13 and 45 years of age with Hartofilakidis type-A hip dysplasia. All of these patients underwent periacetabular osteotomy (PAO) between November 2021 and February 2023. An additional 76 individuals of comparable age and sex but without hip dysplasia were selected from the general population to serve as healthy controls. The Beighton 9-point scoring system was used to evaluate joint hypermobility, and a score of ≥4 was defined as generalized joint hypermobility. Standing anteroposterior pelvic radiographs were reviewed. For patients with DDH, the lateral center-edge angle, Tönnis angle, Sharp angle, lateralization of the femoral head, and patient-reported outcomes (iHOT-12, HHS, and WOMAC) were also collected to determine the radiographic severity or clinical symptoms of DDH. Patients with DDH had an elevated prevalence of generalized joint hypermobility compared with that in the healthy population (27% versus 12%; p = 0.009). Among patients with DDH, those with concomitant generalized joint hypermobility had lower lateral center-edge angles (3.55° versus 9.36°; p = 0.012), greater lateralization of the femoral head (13.78 versus 12.17 mm; p = 0.020), greater standardized lateralization of the femoral head (0.64 versus 0.54; p = 0.009), and lower iHOT-12 scores (35.22 versus 40.96; p = 0.009) than did those without concomitant generalized joint hypermobility. Further multivariable linear regression analysis revealed that higher Beighton scores and younger age were predictive of more severe hip dysplasia. However, the Beighton score was not found to be independently associated with patient-reported outcomes according to multivariable linear regression analysis. The prevalence of generalized joint hypermobility was greater in patients with DDH than in healthy controls. A higher degree of joint hypermobility was also correlated with more severe hip dysplasia. These results suggest that joint laxity, in addition to bone or cartilage factors, is an important factor related to DDH. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Primary leiomyosarcoma of epididymis: a case report

BackgroundLeiomyosarcoma is a tumor that can develop in any organ that contains smooth muscles. Although leiomyosarcoma is common, its epididymal localization is quite rare.Case presentationA 79-year-old male Chinese Han patient presented with mild pain in the right groin and scrotum for 3 years concomitant with right scrotal swelling. Ultrasonography and magnetic resonance imaging of the scrotum showed a irregular and heterogeneous mass that was extratesticular. Right high orchiectomy was performed, and pathological examination of the resected specimen confirmed the diagnosis of leiomyosarcoma of the epididymis with surgical margins clear of tumor.ConclusionEpididymal leiomyosarcoma is rare and difficult to diagnose preoperatively. The final diagnosis of epididymal leiomyosarcoma requires histologic examination. Resection must be extensive and complete. The effect of chemotherapy and radiation on the epididymal leiomyosarcoma remains unclear. Recurrence is common, so follow-up is necessary.

Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia

Response to antipsychotic drugs (APD) varies greatly among individuals and is affected by genetic factors. This study aims to demonstrate genome-wide associations between copy number variants (CNVs) and response to APD in patients with schizophrenia. A total of 3030 patients of Han Chinese ethnicity randomly received APD (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, haloperidol and perphenazine) treatment for six weeks. This study is a secondary data analysis. Percentage change on the Positive and Negative Syndrome Scale (PANSS) reduction was used to assess APD efficacy, and more than 50% change was considered as APD response. Associations between CNV burden, gene set, CNV loci and CNV break-point and APD efficacy were analysed. Higher CNV losses burden decreased the odds of 6-week APD response (OR=0.66 [0.44, 0.98]). CNV losses in synaptic pathway involved in neurotransmitters were associated with 2-week PANSS reduction rate. CNV involved in sialylation (1p31.1 losses) and cellular metabolism (19q13.32 gains) associated with 6-week PANSS reduction rate at genome-wide significant level. Additional 36 CNVs associated with PANSS factors improvement. The OR of protective CNVs for 6-week APD response was 3.10 (95% CI: 1.33-7.19) and risk CNVs was 8.47 (95% CI: 1.92-37.43). CNV interacted with genetic risk score on APD efficacy (Beta=-1.53, SE=0.66, P=0.021). The area under curve to differ 6-week APD response attained 80.45% (95% CI: 78.07%-82.82%). Copy number variants contributed to poor APD efficacy and synaptic pathway involved in neurotransmitter was highlighted. National Natural Science Foundation of China, National Key R&D Program of China, China Postdoctoral Science Foundation.

Association of genetic variations of 3′-UTR in clopidogrel pharmacokinetic-relevant genes with clopidogrel response in Han Chinese patients with coronary artery disease

Dual antiplatelet therapy with aspirin and clopidogrel has reduced ischemic vascular events significantly. Genetic influence, especially those in clopidogrel pharmacokinetic-relevant genes partially accounts for interindividual pharmacodynamic variability of clopidogrel. However, most studies have concentrated on the genetic variations in introns, exons, or promoters of the candidate genes, and the association between genetic variations in 3′-UTR in clopidogrel pharmacokinetic-relevant genes and clopidogrel response is unknown. In our study, ten different algorithms were applied to pick potential miRNAs targeting the clopidogrel pharmacokinetic-relevant genes. Furthermore, the correlation between miRNA expression profiles and mRNA expression of corresponding clopidogrel pharmacokinetic-relevant genes was analyzed. Through comprehensive analysis, including bioinformatics prediction and correlation analysis of miRNA and mRNA expression profiles, miR-218–5p and miR-506–5p were supposed to regulate the expression of PON1 via binding with its 3′-UTR. Moreover, PON1 rs854551 and rs854552 were located in miRNA recognizing sequences and may serve as potential miRSNPs possibly affecting PON1 expression. The rs854552 polymorphism was genotyped and platelet reactivity index (PRI) indicative of clopidogrel response was measured in 341 Chinese coronary artery disease (CAD) patients 24 h after administration of 300 mg clopidogrel. Our results showed that PON1 rs854552 had a significant influence on PRI in CAD patients, especially in patients with CYP2C19 extensive metabolic phenotype. In conclusion, PON1 rs854552 polymorphisms may affect clopidogrel response. Bioinformatics prediction followed by functional validation could aid in decoding the contribution of unexplained variations in the 3′-UTR in drug-metabolizing enzymes on clopidogrel response.

Dose adjustment of paroxetine based on CYP2D6 activity score inferred metabolizer status in Chinese Han patients with depressive or anxiety disorders: a prospective study and cross-ethnic meta-analysis

Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype onparoxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses. After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P=0.03 and P=0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population. Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach. National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.

Presence of Epstein-Barr virus in cerebrospinal fluid is associated with increased mortality in HIV-negative cryptococcal meningitis.

Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P=0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P=0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.

Population pharmacokinetics of intravenous daptomycin in critically ill patients: implications for selection of dosage regimens.

Daptomycin is gaining prominence for the treatment of methicillin-resistant Staphylococcus aureus infections. However, the dosage selection for daptomycin in critically ill patients remains uncertain, especially in Chinese patients. This study aimed to establish the population pharmacokinetics of daptomycin in critically ill patients, optimize clinical administration plans, and recommend appropriate dosage for critically ill patients in China. The study included 64 critically ill patients. Blood samples were collected at the designated times. The blood daptomycin concentration was determined using validated liquid chromatography-tandem mass spectrometry. A nonlinear mixed-effects model was applied for the population pharmacokinetic analysis and Monte Carlo simulations of daptomycin. The results showed a two-compartment population pharmacokinetic model of daptomycin in critically ill adult Han Chinese patients. Monte Carlo simulations revealed that a daily dose of 400mg of daptomycin was insufficient for the majority of critically ill adult patients to achieve the anti-infective target. For critically ill adult patients with normal renal function (creatinine clearance rate >90mL/min), the probability of achieving the target only reached 90% when the daily dose was increased to 700mg. For patients undergoing continuous renal replacement therapy (CRRT), 24h administration of 500mg met the pharmacodynamic goals and did not exceed the safety threshold in most patients. Therefore, considering its efficacy and safety, intravenous daptomycin doses are best scaled according to creatinine clearance, and an increased dose is recommended for critically ill patients with hyperrenalism. For patients receiving CRRT, medication is recommended at 24h intervals.

Can neurocognition, brain neurotrophic factor, triglyceride, and total cholesterol predict suicidal ideation in first-episode Han Chinese patients with schizophrenia?

Previous studies have suggested that the suicide rate of patients with schizophrenia is high. This study investigates factors influencing suicidal ideation in first-episode schizophrenia patients, focusing on cognitive function, brain-derived neurotrophic factor (BDNF), triglyceride (TG), and total cholesterol (TC) in patients with first-episode schizophrenia. A total of 123 patients with first-episode schizophrenia and 38 healthy controls were included in the study. The patients were divided into suicidal and nonsuicidal ideation groups based on the Beck Scale for Suicidal Ideation, and they were assessed with Positive and Negative Syndrome Scale(PANSS). Cognitive function was assessed using the Chinese version of the MATRICS consensus cognitive battery (MCCB) and the serum BDNF, TG, and TC were detected. The main statistical methods include t-test, χ2 test, multivariate logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and the DeLong test. 26.02% of patients exhibited suicidal ideation. Higher PANSS and TC levels were risk factors, while higher MCCB scores and BDNF levels were protective factors. ROC analysis indicated AUCs of 0.630, 0.724, and 0.762 for serum BDNF, PANSS, and MCCB, respectively, with a combined AUC of 0.870. Serum BDNF level, PANSS score, and MCCB score can be used as auxiliary predictors of suicidal ideation in schizophrenic patients. Combining these three indicators can effectively predict suicidal ideation in schizophrenic patients.

Genetic variability in stroke patients: CYP2C19 polymorphisms unraveled

ObjectiveTo study the distribution characteristics of CYP2C19 polymorphisms in patients suffering from stroke in Han Chinese patients.MethodPCR and DNA microarray chip technology were used to detect the CYP2C19 genotype of 549 patients with stroke, and the genotype, allele frequency and metabolic type of patients with different sexes, ages and types of infarctions and the independent risk factors for clopidogrel resistance were analyzed.ResultsSix genotypes were detected in these 549 patients. A total of 233 (42.44%) patients had the heterozygous allele *1/*2, which was the most prevalent, followed by the homozygous wild-type allele *1/*1 (191, 34.79%). A total of 30 (5.46%) patients possessed the heterozygous allele *1/*3, and 65 (11.84%) patients had the homozygous mutant allele *2/*2. Twenty-nine (5.28%) patients had the compound heterozygous mutant allele *2/*3, and only 1 patient had the homozygous mutant allele *3/*3. The distribution of genotypes, alleles, and metabolic types did not change significantly (P > 0.05) by sex, age, or type of stroke. In addition, no independent risk factors for clopidogrel resistance were found in this analysis.ConclusionThe distribution of CYP2C19 genotypes, allele frequencies, and metabolic types in patients with stroke in Han Chinese patients were not correlated with sex, age, or infarction type. The possibilities of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hyper-LDL-cholesterolemia and high blood pressure were not statistically associated with CYP2C19 genotypes. CYP2C19 gene polymorphism detection is recommended for patients who are available, and during treatment, the CYP2C19 genotype can be used to guide personalized precise medication use in patients with stroke.