Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective:To determine the risk factors for permanent nerve damage (PND) after aortic arch surgery in patients with acute type A aortic dissection (AAAD).Methods:This was a retrospective case-control study. The medical records from patients of both sexes with AAAD, aged > 18 yr, of American Society of Anesthesiologists Physical Status classification IV, who underwent aortic arch surgery in the Second Hospital of Hebei Medical University from December 2018 to December 2023, were collected. The patients were divided into non-PND group and PND group according to whether PND occurred after operation. The preoperative data of patients were collected, including age, gender, body mass index; comorbidities (hypertension, coronary heart disease, diabetes mellitus), history of smoking, history of stroke, and history of cardiovascular surgeries; syncope at onset, preoperative low SpO 2, preoperative low systolic blood pressure, and preoperative low diastolic blood pressure. The intraoperative data included surgical procedure (total aortic arch replacement or half aortic arch replacement), selective antegrade cerebral perfusion during operation, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, post-parallel time, moderate hypothermia circulatory arrest time, nasopharyngeal temperature and rectal temperature during circulatory arrest, and BIS value during circulatory arrest; blood pressure during cardiopulmonary bypass and after restoration of heart beat; the incidence of dysfunction after recovery of heart beat and difficulty in hemostasis after termination of CPB. The aforementioned indicators were analyzed for difference, and the indicators with P<0.05 were included in the multivariate logistic regression analysis. Results:A total of 292 patients were ultimately included, among which 73 developed postoperative PND, resulting in an incidence of 25.0%. The results of multivariate logistic regression analysis showed that age ≥62 yr ( OR=3.783, 95% confidence interval [ CI] 1.513-10.346, P=0.006), preoperative hypertension ( OR=2.230, 95% CI 1.118-4.715, P=0.028), syncope at onset ( OR=3.001, 95% CI 1.343-6.710, P=0.007), BIS value > 14 during circulatory arrest ( OR=2.439, 95% CI 1.249-4.755, P=0.009) and difficult hemostasis after termination of CPB ( OR=3.465, 95% CI 1.758-6.882, P<0.001) were risk factors for PND after surgery. Conclusions:Age ≥ 62 yr, history of hypertension, syncope at onset, BIS value greater than 14 during circulatory arrest and difficulty in hemostasis after termination of CPB are risk factors for PND after aortic arch surgery in patients with AAAD.

Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.

OBJECTIVE To construct a comprehensive evaluation index system for anti-lung cancer drugs， and to provide a basis for drug selection and rational clinical use. METHODS Based on the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs （2021 edition for trial use）， a preliminary evaluation index system framework and an index preselection pool were initially formulated through literature analysis. The evaluation indices were then selected and modified by using the Delphi method. The weights of each index were determined through expert scoring and relevant calculations， thereby establishing a comprehensive evaluation index system for anti-lung cancer drugs. Referred to Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions， scoring detailed rules for clinical comprehensive evaluation indexes of anti-lung cancer drugs were formulated. The constructed comprehensive evaluation index system and scoring detailed rules were applied to conduct empirical evaluation of the anti-lung cancer drug pembrolizumab. RESULTS The constructed comprehensive evaluation index system for anti-lung cancer drugs included 6 primary indicators and 15 secondary indicators. The weights of the primary indicators were as follows： safety （18）， efficacy （38）， economy （15）， innovation （9）， suitability （10）， and accessibility （10）. The scoring detailed rules for the comprehensive evaluation index system for anti-lung cancer drugs had been preliminarily established. The results of empirical evaluation showed that the comprehensive evaluation score （61 points） of pembrolizumab combined with chemotherapy regimen was higher than that of the monotherapy chemotherapy regimen （56 points）. The former demonstrated superior efficacy， innovation and suitability compared to the latter， while the latter exhibited better safety and economy. CONCLUSIONS The constructed comprehensive evaluation index system for anti-lung cancer drugs has the potential for generalizability and practical application， providing a reference basis for rational clinical drug use.

Objective:To develop a constant temperature disinfection device and evaluate its clinical effect in perineal disinfection after delivery.Methods:A total of 300 cases of puerpera who met the inclusion and exclusion criteria were selected from Heping Hospital Affiliated to Changzhi Medical College from November to December 2020. The study was designed as a randomized control study. Subjects were randomly divided by random digit table into the control group and the experimental group of 150 cases respectively. The former used conventional methods for perineal disinfection after delivery. The latter performed perineal disinfection assisted by a thermostatic disinfection device. The temperature comfort of perineal disinfection and the perineal wound healing of perineal tear or lateral incision were compared between two groups.Results:The score of temperature comfort feeling of puerpera in the control group and the experimental group was 3 (1.5) and 5 (0), respectively. The maternal temperature comfort feeling score in the experimental group was higher, and the difference between the two groups was statistically significant ( Z=-13.78, P<0.05). There was no grade C healing of perineal wounds in the two groups. The composition ratios of grade A and grade B healing of perineal wounds in the control group were 89.61% (69/77) and 10.39% (8/77), and those in the experimental group were 93.75% (90/96) and 6.25% (6/96). The healing of perineal wound in the latter group was better, but the difference between the two groups was not statistically significant ( Z=0.99, P>0.05). Conclusions:The constant temperature disinfection device meets the clinical nursing needs, enhances the comfort experience of puerpera, and has certain effect on promoting the healing of perineal wound after delivery.

The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

Objective:To investigate the prevalence and genotype distribution of high-risk human papillomavirus (HR-HPV) and the correlation between cervical lesions and analyze the risk factors for HR-HPV infection.Methods:In June 2018, a population-based study for cervical cancer screening in Tuoli county of Xinjiang Uygur Autonomous Region was conducted. A total of 2 000 Kazak women aged 25-64 years were included in the study. Three cervical exfoliated cells samples were collected from them for careHPV, PCR HPV, p16 INK4a, and liquid-based cytology (LBC) tests. Women with any positive test were referred for colposcopy with biopsies taken at abnormal sites. Histo-pathological diagnoses were used as the gold standard. Results:The overall prevalence of HPV was 14.55%, among which the infection rate of HR-HPV was 12.90%, which was even higher in the 50-54 years age group. The most prevalent genotypes of HR-HPV were HPV16 (2.80%), HPV51(2.35%), HPV52 (1.70%), HPV56 (1.50%), and HPV39 (1.20%). The most common HPV infection was a single infection (71.48%). In the age group of 50-54 years, the multiple infection rates were higher, with the majority of double infection (69.88%), and HPV42 and 56 were the most common co-infection types. HPV16 (31.82%), HPV51 (27.27%) and HPV18 (13.64%) were higher in cervical intraepithelial neplasia grade 1, HPV16 (57.14%) was higher in cervical intraepithelial neplasia grade 2, and HPV16 (55.56%) and HPV18 (33.33%) were higher in cervical intraepithelial neplasia grade 3 or worse. Results from the multivariate logistic regression analysis showed that higher education, menopause, and syphilis infection increased the HPV infection.Conclusions:The most common prevalence genotypes of HR-HPV among Kazak women were HPV16, HPV51, and HPV52. The infection rate of HR-HPV among Kazak women was correlated with education level, menopausal status, and syphilis infection. Measures should be taken targeting high-risk factors. This result suggests that STD patients and women aged 50 and above should be encouraged for screening.

Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d)as initial or salvage treatment for invasive pulmonary aspergillosis.Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital,Fudan University were retrospectively reviewed.According to the anti-fungal treatment before high-dose caspofungin application,patients were divided into initial treatment group and salvage treatment group.Patients' clinical data and laboratory data were collected.The characteristics,clinical efficacy,adverse reactions,one-year survival rate and the overall effective rate were evaluated.The prognosis of the two groups was compared by Kaplan-Meier analysis.Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases.Five patients were initially treated with high-dose caspofungin for 68 (62) days.At week 12,one patient achieved complete response,3 patients achieved partial response,and the overall effective rate was 80％ (4/5).Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days,of which one patient got complete response at week 12,10 had partial response,and the overall effective rate was 68.75％ (11/16).One-year follow-up showed that no patient died in the initial treatment group,and the one-year survival rate was 100％ (5/5).In salvage treatment group,3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25％ (13/16).During treatment,one patient had elevated total bilirubin,which was possibly associated with high-dose caspofungin.Conclusions High-dose caspofungin regimen has good efficacy and safety,both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis.

Type 2 diabetes (T2D) has been associated with a high prevalence of depression.We aimed to determine the causal relation by performing a Mendelian randomization (MR) study using 34 T2D risk genetic variants validated in East Asians as the instrumental variable (IV). An MR analysis was performed involving 11 506 participants from a large longitudinal study. The T2D genetic risk score (GRS) was built using the 34 typical T2D common variants. We used T2D_GRS as the IV estimator and performed inverse-variance weighted (IVW) and Egger MR analysis. The T2D_GRS was found to be associated with depression with an OR of 1.21 (95% CI: 1.07-1.37) after adjustments for age, sex, body mass index, current smoking and drinking, physical activity, education, and marital status. Using T2D_GRS as the IV, we similarly found a causal relationship between genetically determined T2D and depression (OR: 1.84, 95% CI: 1.25-2.70). Though we found no association between the combined effect of the genetic IVs for T2D and depression with EggerMR(OR: 0.95, 95%CI: 0.42-2.14), we found an association for T2D and depression with IVW (OR: 1.75, 95% CI: 1.31-2.46) after excluding pleiotropic SNPs. Overall, the MR analyses provide evidence inferring a potential causal relationship between T2D and depression.
Aged ; Causality ; China ; epidemiology ; Depression ; epidemiology ; etiology ; Diabetes Mellitus, Type 2 ; complications ; genetics ; psychology ; Female ; Genetic Variation ; Genotype ; Humans ; Linear Models ; Longitudinal Studies ; Male ; Mendelian Randomization Analysis ; Middle Aged ; Polymorphism, Single Nucleotide ; Psychiatric Status Rating Scales ; Risk Factors ; Sensitivity and Specificity

Objective To examine the heritability of neurocognitive functions in bipolar I disorder(BD-I)families and BD-associated cognitive endophenotypes. Methods Seventy-nine nuclear families consisting of euthymic BD-I probands and their healthy parents were recruited. Cognitive functions including attention, working memory, processing speed and executive function were evaluated by 7 classic neurocognitive tests, and the heritability of neuroconitive functions in these families was estimated using parent-offspring regression indexes of quantitative traits.Furthermore,the heritable cognitions were compared between 79 BD probands and 140 normal controls. Results After adjusted by age and education,mistake numbers of Trail Making Test A(TMT-A),total score and completed mission numbers of Tower of Hanoi (TOH) were significantly heritable (P<0.05). The comparison of these heritable cognitions between patients and normal controls showed that TOH total score and TOH completed mission numbers were significantly impaired in the patient group (P<0.05). Conclusion Processing speed and executive function are probably heritable in BD nuclear families. Executive function impairments may be disease-related which could be candidate endophenotypes for bipolar disorder.