Analysisof neurological disease spectrum among hospitalized patients in a tertiary hospital from 2018 to 2022 / 现代医院

Objective To analyze the changes in the disease spectrum of hospitalized patients with neurological diseases in a tertiary hospital in the past 5 years,in order to effectively develop targeted disease prevention and treatment strategies.Methods Collect case data of neurological diseases in a tertiary hospital from January 1,2018 to December 31,2022,and use ICD-10 coding for disease classification,and analyze the disease type,gender,age groups,and other factors.Results A total of 9060 patients with neurological diseases were admitted in the past five years.In 2020,the number of discharged patients affected by the COVID-19 was the smallest,accounting for 15.96% ,and in 2022,the number was the largest,accounting for 24.05% .The number of cases showed an increasing trend.There was no statistically significant difference in the composition of male and female patients;There is a statistically significant difference in the number of cases among patients of different age groups,and the incidence categories are different;The top 10 diseases in the ranking of neurological diseases are:transient ischemic attack,headache,spinal nerve disease,neurological disorders,epilepsy,Parkinson's disease,sleep disorders,paralysis,other brain diseases,hydrocephalus.The distribution of the top 10 diseases by gender has statistical significance.Conclusion The hospital can formulate the diagnosis and treatment technology for different age groups according to the distribution characteristics of disease spectrum,carry out comprehensive prevention and treatment measures for key groups,strengthen the construction of key special-ties and allocate health resources properly.

Clinical diagnosis, treatment, and genetic analysis in 4 cases of congenital hyperinsulinemia / 中国新生儿科杂志

Objective:To investigate the clinical diagnosis, treatment, and genetic variations of neonates with congenital hyperinsulinism (CHI).Methods:The clinical data of CHI newborns admitted to the Provincial Hospital Affiliated to Shandong First Medical University from September 2018 to April 2022 were retrospectively analyzed.Results:Four cases of CHI were included, three of whom were full-term infants and all were macrosomic, while one was a premature infant. One infant was born to a mother with gestational diabetes mellitus, and 1 had a family history of hypoglycemia. All the 4 patients presented with weak response, 3 with drowsiness, 1 with hypotonia and 1 with convulsions. Cranial MRI indicated abnormal signals in the occipital lobe cortex in 1 case. Gene sequencing revealed homozygous variation c.799C>G in KCNJ11 gene for 1 case, and heterozygous variations c.4477C>T, c.3540C>G, c.683G>A and c.4536C>A in ABCC8 gene for 3 cases respectively and all these variations were identified as pathogenic mutations. Notably, the c.799C>G variant in KCNJ11 gene as well as the c.3540C>G and c.4536C>A variants in ABCC8 gene were reported for the first time. Among infants with ABCC8 gene variations, two showed no response to diazoxide treatment while one patient with KCNJ11 gene variation responded effectively. The parents of the patient with hypoglycemic brain injury gave up treatment. Three other cases were discharged from hospital after improvement and followed up to 1 year old. 2 patients had stable blood glucose after ceasing medication, and 1 patient still required intermittent oral glucose to maintain normal blood glucose level.Conclusions:CHI can lead to hypoglycemic brain injury. Clinically, infants large for gestational age or with a family history of diabetes and hypoglycemia should be monitored for blood glucose early after birth, to identify CHI as early as possible and actively treat it. Different gene variants have different therapeutic responses.

Serum TSH levels in women aged 40 and above : association with lifespan and 10-year mortality / 中华内分泌代谢杂志

Objective:To investigate the relationship between thyroid-stimulating hormone(TSH) levels and 10-year mortality in women aged 40 years and older.Methods:Residents aged 40 and over in urban areas of Guiyang City who participated in the " Epidemiological Study of Cancer Risk in Patients with Type 2 Diabetes in China(REACTION)" were followed up in 2011. Finally, 5 614 people were enrolled, and the baseline general information, physical examination and TSH detection were carried out. The average follow-up was(9.77±1.55) years, and the treatment and death of thyroid-related diseases were recorded. The Cox proportional hazards model was used to analyze the relationship between TSH level and 10-year mortality in middle-aged and elderly women, and plotting survival time curves(Kaplan-Meier curves) to study the association between elevated TSH levels and lifespan in subjects under 65 years old. Results:The multivariate Cox proportional hazards model showed that compared with the normal group, after multivariate adjustment, the risk of death in the TSH increased group was decreased( HR=0.644, 95% CI 0.478-0.868, P<0.05); after stratifying the elevated TSH group, the risk of death was decreased in the slightly elevated TSH group( HR=0.566, 95% CI 0.405-0.791, P<0.001); the elevated TSH group was further stratified by age. In the group under 65 years old, compared to the normal group, the mildly elevated group showed a reduced risk of mortality( HR=0.429, 95% CI 0.245-0.751, P=0.003). In the group aged 65 and above, there were no statistically significant differences in mortality risk between the mildly elevated group, severely elevated group, and the normal group( P>0.05). In the group under 65 years old, the K-M curve indicated that the survival rate of the mildly elevated TSH group was significantly higher than that of the normal group( χ2=11.931, P=0.003), the difference was statistically significant. Conclusion:Mildly elevated TSH levels in women aged 40-65 years are associated with a reduced risk of all-cause death and longer lifespan.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Research Progress on Mechanisms of Triggeringreceptor Expressed on Myeloid Cells-2 in Cognitive Dysfunction / 中山大学学报(医学科学版)

The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.

Relationship Between Mindfulness and Affiliate Stigma in Parents of Children with Autism Spectrum Disorder in China: The Mediating Role of Coping Styles

Purpose@#This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China.MethodBetween February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. @*Results@#(1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = −0.38, −0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = −0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. @*Conclusions@#Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

Transcutaneous Electrical Acupoint Stimulation Promotes PGC-1α Mediated Mitochondrial Biogenesis and Antioxidant Stress to Protect Cognitive Function in Vascular Dementia Rats / 生物化学与生物物理进展

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

A Methodological Investigation of Hair Proteomics-based Differentiation of Individual Traits / 生物化学与生物物理进展

ObjectiveHair is an essential skin appendage, primarily composed of keratins and keratin-associated proteins. The protein composition and proportion of hair samples vary among different races and sexes. Currently, there is a lack of efficient methods to extract hair proteins. This study aims to explore the application of quantitative hair proteomics in distinguishing individual hair characteristics. MethodsBased on the exploration of sample processing and lysis buffer using three hair samples, we developed a stable and efficient hair protein extraction method, named PLEE (PTM lab for protein extraction from hair with high efficiency). We used the PLEE method to extract seven human hair samples and performed proteomic experiments on them using in-gel digestion method to produce data for analyzing hair protein composition and proportion among individuals. ResultsA total of 274 proteins were identified, among which 107 proteins were commonly present, and the number of non-common proteins ranged from 57-119, with some samples having unique identification proteins. Using the 107 commonly identified proteins for quantitative protein fractionation analysis, various samples were distinguished by clustering and principal component analysis, and technical repeated samples were merged, indicating the stability of the process. In addition, 10 key proteins (KRT33A, KRTAP9-6, KRT83, KRTAP7-1, KRT32, BLMH, KRT38, KRTAP11-1, NPAS1, KRTAP4-3) with large differences between individuals and stable protein identification within the same individual were screened. ConclusionThe protein composition of hair varies among different individuals, and the 10 selected proteins are expected to be key proteins for distinguishing individual hair characteristics and have significant potential applications in individual identification and criminal investigation.

Acupuncture for chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the short-term efficacy, long-term efficacy and safety of acupuncture for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).@*METHODS@#Forty-two patients with CP/CPPS were randomly divided into an acupuncture group (21 cases, 1 case dropped off) and a sham acupuncture group (21 cases). The patients in the acupuncture group were treated with acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6); the needling depth of Zhongliao (BL 33) and Huiyang (BL 35) was 60 to 80 mm, while Shenshu (BL 23) and Sanyinjiao (SP 6) was directly punctured of 30 mm. The patients in the sham acupuncture group were treated with acupuncture at non-acupoints, including points 2 cm next to Shenshu (BL 23), Zhongliao (BL 33) and Huiyang (BL 35), and the midpoint of the connecting line between the spleen meridian and the kidney meridian. All the non-acupoints were treated with directly puncture of 2 to 3 mm. The needles were left for 30 min in both groups, once every other day in the first four weeks, three times a week, and twice a week in the next four weeks, totally 20 treatments. Before treatment, after treatment and in follow-up of 24 weeks after treatment completion, the National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) score and urinary flow rate were observed in both groups; the clinical efficacy and safety were evaluated.@*RESULTS@#Compared with those before treatment, the pain and discomfort scores, urination symptoms scores, quality of life scores and total scores of NIH-CPSI in both groups were reduced after treatment in the two groups (P<0.01), while each item score and total score of NIH-CPSI in the acupuncture group were reduced in follow-up (P<0.01, P<0.05). After treatment and in follow-up, each item score and total score of NIH-CPSI in the acupuncture group were lower than those in the sham acupuncture group (P<0.05, P<0.01). After treatment, the maximum and average urinary flow rates in the acupuncture group were higher than those before treatment (P<0.05), and the average urinary flow rate in the acupuncture group was higher than that in the sham acupuncture group (P<0.05). The total effective rate was 75.0% (15/20) in the acupuncture group, which was higher than 42.9% (9/21) in the sham acupuncture group (P<0.05). No significant adverse reactions were observed in the two groups, and there was no significant difference in the incidence of adverse reactions between the two groups (P>0.05).@*CONCLUSION@#Acupuncture could effectively alleviate the clinical symptoms, improve quality of life, and has a sustained, safe and reliable therapeutic effect in patients with CP/CPPS.

Advances in molecular function of p62 protein and its role in diseases / 生物工程学报

Sequestosome 1 (SQSTM1/p62) is a selective autophagy adaptor protein that plays an important role in the clearance of proteins to be degraded as well as in the maintenance of cellular proteostasis. p62 protein has multiple functional domains, which interact with several downstream proteins to precisely regulate multiple signaling pathways, thereby linking p62 to oxidative defense systems, inflammatory responses and nutrient sensing. Studies have shown that mutation or abnormal expression of p62 is closely related to the occurrence and development of various diseases, including neurodegenerative diseases, tumors, infectious diseases, genetic diseases and chronic diseases. This review summarizes the structural features and molecular functions of p62. Moreover, we systematically introduce its multiple functions in protein homeostasis and regulation of signaling pathways. Furthermore, the complexity and versatility of p62 in the occurrence and development of diseases are summarized, with the aim to provide a reference for understanding the function of p62 protein and facilitating related disease research.

Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD / 生理学报

The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1β (IL-1β), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1β, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

Incidence and clinical characteristics of engraftment syndrome after syngeneic hematopoietic stem cell transplantation in patients with hematological diseases / 中华血液学杂志

Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses / 中华儿科杂志

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Voltage Dependent Anion Channel 1 Mediated Inflammation and Obstructive Sleep Apnea Syndrome / 中山大学学报(医学科学版)

VDAC1（voltage dependent anion channel 1）is an important channel protein on the outer mitochondrial outer membrane， which regulates mitophagy， participates in the regulation of inflammatory cytokines and the activation of the inflammasome， hence being crucial to the inflammatory response. Patients with obstructive sleep apnea syndrome （OSAS） suffer neuroinflammation due to intermittent hypoxia and increased oxidative stress， leading to chronic damage and neuronal cell apoptosis， and eventually develop cognitive impairment. Since OSAS patients' cognitive impairment is significantly influenced by inflammation， and VDAC1 regulates the activation of the inflammasome， the relationship between OSAS and VDAC1， mitophagy， as well as inflammation are reviewed here. We hope that this study can provide a new breakthrough in mitophagy and inflammation in patients with cognitive dysfunction caused by OSAS.

Risk factors and complication of hemodynamically significant patent ductus arteriosus in preterm infants with gestational age <32 weeks / 国际儿科学杂志

Objective:To study the risk factors and complications of hemodynamically significant patent ductus arteriosus(hsPDA)in preterm infants <32 weeks.Methods:From January 2021 to March 2022, a total of 150 premature infants with gestational age <32 weeks admitted to the Neonatal Intensive Care Unit of Liaocheng People′s Hospital were enrolled.Nine patients who did not meet the requirements were excluded and a total of 141 infants were finally analyzed retrospectively, including PDA group with 95 cases and non-PDA group with 46 cases.According to whether hsPDA existed or not, PDA group were dirided into hsPDA group with 42 cases and non-hsPDA group with 53 cases.Univariate and regression analyses were used to determine the risk factors and complication of hsPDA.Results:Univariate analysis showed that gestational age( t=-6.861, P<0.01), birth weight( t=-4.392, P<0.01), mode of delivery( χ2=9.018, P<0.01), caffeine( χ2=4.337, P<0.05) and suffocation( χ2=7.918, P<0.01)were associated with hsPDA.Logistic regression analysis showed that gestational age( OR=2.435, P<0.01, 95% CI: 1.669~3.552)was an independent risk factor for hsPDA in gestational age <32 weeks preterm infants.The incidences of necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity in the hsPDA group were higher than those in the non-hsPDA group( P<0.05). Conclusion:Gestational age is an independent risk factor for hsPDA with gestational age <32 weeks.Necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity are related complications of hsPDA.

Status quo and influencing factors of grief in maternal spouses after perinatal loss / 中国实用护理杂志

Objective:To investigate the status of grief among maternal spouse after perinatal loss, and analyze its influencing factors, so as to provide some reference for male grief supporting strategic.Methods:Using the convenient sampling method, 180 male spouses of hospitalized women in the Department of Obstetrics from Nanjing Maternity and Child Health Care Hospital from March to October 2022 were recruited. A cross-sectional survey was conducted by the general questionnaire, the Perinatal Grief Scale, the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version, the Social Support Rating Scale, and the Simplified Coping Style Questionnaire.Results:The overall score of the Perinatal Grief Scale in male spouses of women who experienced a perinatal loss was (61.57 ± 14.14) points. The score of the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version was (121 ± 14.42) points, the score of the Social Support Rating Scale was (34.23 ± 7.21) points, and the score of the Simplified Coping Style Questionnaire was (36.08 ± 7.64) points. Multiple linear regression analysis showed that participation in fetal interaction, loss of fetal age, social support and family adaptability were the main factors affecting male grief ( P<0.05). Conclusions:The grief among male spouses of women who experienced a perinatal loss is at a low level. The clinical medical staff can refer to the influencing factors and implement effective support, such as respecting the male's father status, coordinating social support resources, and improving the family's coping ability, in order to alleviate men's grief and help them return to normal life.