Effects of osthole on renal oxidative stress injury in aged spontaneously hypertensive rats by regulating PI3K/Akt/mTOR signaling pathway / 中国临床药理学与治疗学

AIM: To explore the mechanism of osthole on elderly spontaneously hypertensive rats. METHODS: 20-month-old spontaneously hypertensive rats (SHRs) and healthy Wistar-Kyoto (WKY) rats were purchased. SHRs were treated with osthole (i.g.) for 8 weeks. The systolic blood pressure and diastolic blood pressure of rats were monitored. Hematoxylin-eosin staining (H&E), periodic acid-schiff staining (PAS) and Masson staining were used to observe the pathological changes of rat kidney tissues. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in rat kidney was detected by ELISA kit. PI3K/Akt/mTOR signaling pathway related proteins were detected by western blot. RESULTS: Osthole reduced the systolic and diastolic blood pressure of SHRs, improved the histopathological changes of SHRs kidney, reduced the activity of MDA in SHRs kidney, and increased the activity of SOD and GSH. Osthole reduced the levels of p-PI3K, p-Akt and p-mTOR. CONCLUSION: Osthole reduces the activity of PI3K/Akt/mTOR signaling pathway and exerts a protective effect on renal oxidative stress injury in aged spontaneously hypertensive rats.

Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children / 中华儿科杂志

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Clinical study of retrograde intrarenal surgery and miniaturized percutaneous nephrolithotomy in the treatment of lower pole kidney stones with a diameter <1.5 cm / 中华泌尿外科杂志

Objective:To evaluate the clinical efficacy and safety of retrograde intrarenal surgery(RIRS) and miniaturized percutaneous nephrolithotomy(mini-PCNL) in the treatment of lower pole kidney stones with a diameter <1.5 cm.Methods:The data of 95 patients with lower pole kidney stones with a diameter <1.5 cm treated in Renmin Hospital of Wuhan University from June 2017 to October 2020 were retrospectively analyzed. According to different surgical methods, the patients were divided into RIRS group and mini-PCNL group. There were 51 cases in RIRS group and 44 cases in mini-PCNL group. There was no significant difference in age [(48.2±11.4) years vs. (46.4±14.1) years], body mass index [(21.9±2.4) kg/m 2 vs. (20.7±3.2) kg/m 2], gender [male/female: 37/14 vs. 24/20], stone CT [(746.42±164.24)HU vs. (858.62±148.72)HU], creatinine [(71.3±21.6)μmol/L vs. (63.5±20.3)μmol/L], stone location (left/right: 26/25 vs. 23/21), stone diameter [(10.5±2.1) mm vs. (12.5±2.4) mm], infundibulopelvic angle [(43.32±9.42) degrees vs. (43.82±10.34) degrees], infundibular length [(24.92±4.85)mm vs. (24.37±5.26)mm] and infundibular [(9.26±3.04)mm vs.(9.46±2.94)mm] between the two groups ( P>0.05). The operation time, stone-free rate, hospital stay and postoperative complications between the two groups were compared. Results:Compared with the mini-PCNL group, the RIRS group had significantly smaller decrease in postoperative hemoglobin [(1.53±0.92) g/L vs. (4.54±2.46) g/L, P<0.05], the postoperative hospital stay was shorter [(2.52±0.94) d vs. (4.51±1.25)d, P<0.05], and postoperative visual analogue score was lower [(2.43±0.92) vs. (3.24±0.76), P<0.05]. The operation time of the mini-PCNL group was shorter than that of the RIRS group [(42.32±13.28) min vs. (54.24±14.43)min, P<0.05]. There was no significant difference in postoperative complications [5.9% (3/51) vs. 11.4% (5/44), P>0.05], postoperative cveatinine [(71.3±21.6) μmol/L vs. (63.5±20.3) μmol/L, P>0.05], postoperative intestinal function recovery time [(25.46±10.28)h vs. (32.43±9.25)h, P>0.05] and stone-free rate [92.2% (47/51) vs. 97.7% (43/ 44), P>0.05] between the two groups. Conclusions:Both RIRS and mini-PCNL are effective and safe minimally invasive treatments for lower pole kidney stones with a diameter < 1.5 cm. RIRS has shorter operation time, less blood loss, lower pain score and faster postoperative recovery.

Analysis of lysosomal enzyme activity and genetic variants in a child with late-onset Pompe disease / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features, lysosomal enzymatic [acid α-glucosidase (GAA)] activities and genetic variants in a child with late-onset Pompe disease (LOPD).@*METHODS@#Clinical data of a child who had presented at the Genetic Counseling Clinic of West China Second University Hospital in August 2020 was retrospectively analyzed. Blood samples were collected from the patient and her parents for the isolation of leukocytes and lymphocytes as well as DNA extraction. The activity of lysosomal enzyme GAA in leukocytes and lymphocytes was analyzed with or without addition of inhibitor of GAA isozyme. Potential variants in genes associated with neuromuscular disorders were analyzed, in addition with conservation of the variant sites and protein structure. The remaining samples from 20 individuals undergoing peripheral blood lymphocyte chromosomal karyotyping were mixed and used as the normal reference for the enzymatic activities.@*RESULTS@#The child, a 9-year-old female, had featured delayed language and motor development from 2 years and 11 months. Physical examination revealed unstable walking, difficulty in going upstairs and obvious scoliosis. Her serum creatine kinase was significantly increased, along with abnormal electromyography, whilst no abnormality was found by cardiac ultrasound. Genetic testing revealed that she has harbored compound heterozygous variants of the GAA gene, namely c.1996dupG (p.A666Gfs*71) (maternal) and c.701C>T (p.T234M) (paternal). Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1996dupG (p.A666Gfs*71) was rated as pathogenic (PVS1+PM2_Supporting+PM3), whilst the c.701C>T (p.T234M) was rated as likely pathogenic (PM1+PM2_Supporting+PM3+PM5+PP3). The GAA in the leukocytes from the patient, her father and mother were respectively 76.1%, 91.3% and 95.6% of the normal value without the inhibitor, and 70.8%, 112.9% and 128.2% of the normal value with the inhibitor, whilst the activity of GAA in their leukocytes had decreased by 6 ~ 9 times after adding the inhibitor. GAA in lymphocytes of the patient, her father and mother were 68.3%, 59.0% and 59.5% of the normal value without the inhibitor, and 41.0%, 89.5% and 57.7% of the normal value with the inhibitor, the activity of GAA in lymphocytes has decreased by 2 ~ 5 times after adding the inhibitor.@*CONCLUSION@#The child was diagnosed with LOPD due to the c.1996dupG and c.701C>T compound heterozygous variants of the GAA gene. The residual activity of GAA among LOPD patients can range widely and the changes may be atypical. The diagnosis of LOPD should not be based solely on the results of enzymatic activity but combined clinical manifestation, genetic testing and measurement of enzymatic activity.

Analysis on health-related quality of life of migrant workers with pneumoconiosis in Hunan Province / 中国职业医学

Objective To understand the health-related quality of life (HRQOL) of migrant workers with pneumoconiosis who received basic medical treatment in Hunan Province. Methods A total of 613 migrant workers with pneumoconiosis who received basic medical treatment and assistance in Hunan Province was selected as the study subjects using stratified random sampling method. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to assess their HRQOL. Results The abnormality of the five dimensions of the EQ-5D health description system, from high to low, were as follows： daily activities, mobility, pain/discomfort, anxiety/depression, and self-care, with the abnormal rates of 50.9%, 46.8%, 41.1%, 21.0%, and 14.5%, respectively. The visual analogue scale (VAS) score of EQ-5D was (63.5±18.6) points. Patients with stage Ⅲ pneumoconiosis had high abnormality in mobility, daily activities, and pain/discomfort compared with those with stage Ⅰ and Ⅱ disease (all P<0.02). Patients in stage Ⅱ and Ⅲ of pneumoconiosis had higher incidence of anxiety/depression compared with those with stage I disease (all P<0.02). Patients with complications in addition to pneumoconiosis had higher abnormality in mobility, self-care, and pain/discomfort compared to those with simple pneumoconiosis or those eligible for lung lavage treatment (all P<0.02). Patients with simple pneumoconiosis had a higher incidence of anxiety/depression compared with those eligible for lung lavage treatment (P<0.02). Patients with stage Ⅲ pneumoconiosis had lower average VAS scores compared with stage Ⅰ and Ⅱ patients (all P<0.02). Patients with simple pneumoconiosis or those with complications had lower average VAS scores compared with those eligible for lung lavage treatment (all P<0.05). Conclusion The HRQOL of pneumoconiosis patients among migrant workers needs improvement, especially for patients with stage Ⅲ disease and those with complications. This study indicates the need of optimizing policies, raising the hospitalization expense limit for critically ill patients with stage Ⅲ pneumoconiosis or with complications, and improving their HRQOL.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Correlations between appearance traits and internal quality of Bupleurum scorzonerifolium roots based on theory of "quality evaluation through morphological identification" / 中国中药杂志

It is generally believed that high-quality Bupleurum scorzonerifolium roots possess specific morphological characteristics, being red, robust, and long with strong odor. However, the scientific connotation of these characteristics has not been elucidated. According to the theory of "quality evaluation through morphological identification", we studied the correlations between appearance traits(the RGB value of root surface, root length, root diameter, dry weight, and ratio of phloem to xylem) and content of main chemical components(volatile oils, total saponins, total flavonoids, total polysaccharides, and seven saikosaponins) of B. scorzonerifolium roots. Epson Scanner and ImageJ were used to scan the root samples and measure the appearance traits. Ultraviolet spectrophotometry and HPLC were employed to determine the content of chemical components. The correlation, regression, and cluster analyses were performed to study the correlations between the appearance traits and the content of chemical components. The results showed that the content of volatile oils and saikosaponins were significantly correlated with RGB value, root length, and root diameter, indicating that within a certain range, the roots being redder, longer, and thicker had higher content of volatile oils and saikosaponins. According to the appearance traits and chemical component content, the 14 samples from different producing areas were classified into four grades, and the differences in morphological traits and chemical component content were consistent among different grades. The findings in this study demonstrate that appearance traits(RGB value, root length, and root diameter) can be used to evaluate the quality of B. scorzonerifolium roots. Meanwhile, this study lays a foundation for establishing an objective quality evaluation method for B. scorzonerifolium roots.

Screening and influencing factors of spine problems of children and adolescents aged 6-18 years / 公共卫生与预防医学

Objective To analyze the screening results of spinal problems in children and adolescents aged 6-18 years and the influencing factors of scoliosis to provide reference for the prevention of spinal problems in children and adolescents. Methods Stratified cluster random sampling was used to screen the prevalence of scoliosis among kindergarten to senior high school students in Shiyan city, and a questionnaire survey was conducted among subjects or parents. Multivariate logistic regression was used to analyze the risk factors affecting the occurrence of scoliosis. Results A total of 1 674 children and adolescents were investigated, and 113 cases of scoliosis were detected, with a detection rate of 6.75%. The probability of scoliosis was 1.92% (13/678), 5.35% (28/523) and 17.76% (72/473) in elementary school, junior high school and senior high school students, respectively. The detection rate of scoliosis gradually increased with the increase of education level (χ2 for trend = 5.272, P 12 h (63.72%), daily electronic product use time > 2 h (67.26%), high physical activity > 1 time/d (42.48%) in the past 7 d, and daily outdoor activity time ≤ 2 h (62.83%) were higher than those in the group without scoliosis (P 12 hours (OR=3.258 , 95% CI: 2.562-11.247), daily electronic product use time>2 hours (OR=2.619, 95% CI: 1.935-5.508) , Heavy physical activity in the past 7 days (OR=1.724, 95% CI: 1.347-2.966) , Daily outdoor activity ≤2 h（OR=1.830，95% CI: 1.463-3.103）is a risk factor for scoliosis in children and adolescents (P<0.05). Conclusions The occurrence of scoliosis in children and adolescents is related to gender, nutritional status, and learning habits, and it is necessary to strengthen the screening of high-risk groups in order to reduce the occurrence of scoliosis.

Clinical observation of Ruyi jinhuang powder combined with ICIs in the treatment of advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder / 中国药房

OBJECTIVE To explore the clinical efficacy and safety of Ruyi jinhuang powder for external application combined with immune checkpoint inhibitors （ICIs） in the treatment of patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder. METHODS All patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder were admitted to our hospital from January 2018 to June 2022 and assigned into observation group and control group according to random number table method. Patients in the control group （n＝56） were treated with ICIs （Navulizumab injection/Sintilimab injection/Camrelizumab for injection） 200 mg， ivgtt， 21 days as a treatment cycle. Patients in the observation group （n＝56） were additionally treated with Ruyi jinhuang powder for external application， once a day， on the basis of control group. The therapeutic effects of 2 groups were compared after a treatment cycle. The levels of interleukin-6 （IL- 6）， matrix metalloproteinase-9 （MMP-9）， cyclooxygenase-2 （COX-2）， prostaglandin E2 （PGE2）， carbohydrate antigen 199 （CA199）， alpha-fetoprotein （AFP） and vascular endothelial growth factor （VEGF） in serum were compared between 2 groups before and after treatment. Karnofsky functional status （KPS） score， digital rating scale （NRS） score， total symptom score of traditional Chinese medicine， and the occurrence of adverse reactions were recorded for both groups of patients. RESULTS After treatment， the levels of IL-6， MMP-9， COX-2， PGE2， CA199， AFP， VEGF， NRS score and total symptom score of traditional Chinese medicine in observation group were significantly lower than control group （P＜0.05）， KPS score was significantly higher than the control group （P＜0.05）. The zypp-04） total effective rate and remission rate of the observation group were 64.29% and 80.36%， those of control group were 60.71% and 73.21%. There was no statistical significance between two groups （P＞0.05）. The adverse drug reactions of both groups were mainly nausea and vomiting， liver function injury， fever hlshli@yeah.net and so on； the incidence of adverse reaction in observation group was significantly lower than that of control group （P＜0.05）. CONCLUSIONS In patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder， the combination of Ruyi jinhuang powder for external application and ICIs can help inhibit the secretion of pain mediators， regulate vascular endothelial function， reduce the inflammatory response， promote the recovery of cardiopulmonary function， improve clinical efficacy and has good safety.

Prevalence of job burnout and associated influencing factors among healthcare workers in China / 环境与职业医学

Background Healthcare workers suffer from great internal and external pressure and are prone to burnout. Existing studies have shown that depressive symptoms are important influencing factors of burnout, both of which are closely related to job stress. Objective To analyze overall prevalence of burnout among healthcare workers using a new survey tool developed by our team, and to reveal potential influencing factors related to burnout. Methods A cross-sectional multi-center study was conducted in August–October 2019 and June–September 2020, using multi-stage stratified cluster sampling. A total of 8738 healthcare workers from 22 hospitals in 5 provinces (Shandong, Hubei, Hunan, Guangdong, and Chongqing) of China were selected in this study. A set of survey questionnaires, including the general information questionnaire and the Chinese versions of General Burnout Scale, Core Occupational Stress Scale, Patient Health Questionnaire-9, and Self-administered Sleep Questionnaire were distributed. Independent samples t-test or one-way ANOVA were employed for inter-group comparison of burnout. Spearman correlation was used to evaluate correlations among burnout, depressive symptoms, and occupational stress. Stepwise linear regression was conducted to identify factors independently associated with burnout. Process plug-in was used to test potential mediating effect of depressive symptoms on occupational stress and burnout. Results Of the 8738 questionnaires distributed, 8456 valid questionnaires were collected, and the recovery rate was 96.77%. Among the 8456 healthcare workers, the prevalence of burnout was 58.0%, that of occupational stress was 31.8%, and that of depressive symptoms was 31.0%. Among those with depressive symptoms and occupational stress, the proportions of burnout were 86.7% and 83.7%, respectively. According to the stepwise linear regression analysis, depressive symptoms, occupational stress, work experience, drinking, and marital status were all independent influencing factors of burnout. Especially, depressive symptoms, social support, and organization and reward had significant influences on burnout (b'=0.455, −0.183, 0.220, P<0.001). Depressive symptoms showed mediating effects on occupational stress (and its subscales) and burnout, and the contribution rates of the mediating effects were 41.00%, 47.02%, 43.44%, 56.62%, and 59.45%, respectively. Conclusion Burnout is a prominent problem among healthcare workers in the 5 provinces, with the prevalence of 58.0%. And nearly 1/3 suffering from depressive symptoms and occupational stress, which has a great impact on burnout.

Reliability and validity of General Burnout Scale in multiple populations / 环境与职业医学

Background As one of the common tools for job burnout assessment, Maslach Burnout Inventory-General Survey (MBI-GS), its reliability and validity across different populations in China have not been examined yet. Objective To evaluate the reliability and validity of General Burnout Scale (GBS) by multiple occupational groups through the translation and preliminary test of MBI-GS. Methods Based on the Special Project of Occupational Hazards in Key Populations led by the Institute of Occupational Health and Poison Control, China CDC, key occupational groups in five typical industries were selected by multi-stage stratified cluster sampling, including teachers, firefighters, manufacturing workers, medical staff, and traffic police. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of GBS by single-factor, two-factor, and three-factor structure models. The model fitness was assessed by ratio of the chi-square statistic to the respective degrees of freedom (χ2/ν), root mean square error of approximation (RMSEA), goodness-of-fit index (GFI), comparative fit index (CFI), and parsimony-adjusted non-normed fit index (PNFI). Spearman correlation analysis was used to calculate the criterion validity of GBS with occupational stress, depressive symptoms, and sleep disorders. Cronbach's α coefficient and composite reliability (CR) coefficient were used to evaluate the internal consistency reliability of GBS. Results A total of 3485 subjects were surveyed in this study, 3375 valid questionnaires were recovered with a valid response rate of 96.84%. The results of CFA showed that in the adjusted three-factor structure model of GBS (exhaustion, cynicism, and professional efficacy), the χ2/ν < 4, the RMSEA ranged from 0.032 to 0.069, the GFI > 0.90, the CFI > 0.90, and the PNFI > 0.70, which illustrated a good fitness than that of the single- or the two-factor structure models in different occupational groups. The Spearman correlation analysis results showed that occupational stress, depressive symptoms, and sleep disorders were positively correlated with exhaustion and cynicism dimensions, and negatively correlated with professional efficacy dimension of the GBS, with the \begin{document}$ \left| r \right| $\end{document} ranging from 0.139 to 0.662 (P<0.05) in overall subjects. For traffic police and firefighters, professional efficacy was not correlated with depressive symptoms or sleep disorders (P>0.05). The Cronbach's α coefficients ranged from 0.819 to 0.899, and the CR values ranged from 0.941 to 0.978 in different occupational groups. Conclusion The GBS shows high reliability and validity, as well as good application effects in different occupational groups.

Exploration of pharmaceutical service model in multidisciplinary diagnosis and treatment of rare diseases in children / 中国药房

OBJECTIVE To explore the pharmaceutical service model in multidisciplinary diagnosis and treatment （MDT） of rare diseases in children. METHODS Clinical pharmacists of West China Second University Hospital （hereinafter referred to as “our hospital”） participated in the process of MDT of children’s rare diseases. Clinical pharmacists took part in the entire diagnosis and treatment process of children and established the MDT pharmaceutical service model of children’s rare diseases by formulating drug treatment plans based on evidence-based practice， improving the accessibility of drugs， pharmaceutical monitoring and drug treatment management. RESULTS From January 2021 to April 2022， clinical pharmacists of our hospital had participated in a total of 39 cases of rare diseases MDT in children， including 21 hospitalized children with rare diseases and 18 outpatient com children with rare diseases， involving a total of 23 rare diseases. Clinical pharmacists completed 45 pharmaceutical zhanglingli@scu.edu.cn rounds and 26 pharmaceutical consultations for rare diseases inpatients， 25 outpatients’ MDT and 5 pharmaceutical outpatient service for outpatients with rare diseases， 38 medication educations for inpatients and outpatients with rare diseases and 25 follow-up services for out-of-hospital patients. There were 24 cases （61.54%） of off-label drug use， involving 13 rare diseases and 16 therapeutic drugs， among which off-label drug use registration of 11 drugs had been completed or was in progress. The temporary purchase evaluations of 3 drugs had been completed； 268 cases of medical insurance drug and high-value drug prescription had been reviewed. CONCLUSIONS Our hospital have primarily established a loop pharmaceutical service model of MDT for children with rare diseases， which covers inpatients and outpatients. The model improves the availability and standardization of clinical application of therapeutic drugs， and diagnosis and treatment level for children with rare diseases in our hospital.

Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice / 神经科学通报·英文版

Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.

Analysis of 4 children with DYNC1H1 gene related spinal muscular atrophy with lower extremity predominant 1 / 中华儿科杂志

Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.

A Real-world Study of Anti-PD-1 Antibody Combination Therapy in Advanced Hepatocellular Carcinoma / 肿瘤防治研究

Objective To explore the efficacy, safety, and factors that might influence the efficacy of antiPD-1 antibody-based therapy in advanced hepatocellular carcinoma in the real world. Methods The clinical features, efficacy, and safety in patients with advanced hepatocellular carcinoma who received anti-PD-1 antibody-based therapy were retrospectively analyzed. The survival status was followed-up. Results The objective response and the disease control rate were 21.8% and 76.4%, respectively. The overall incidence of adverse events during treatment was 81.8%, of which the incidence of grade 3/4 adverse events was 14.5%. The incidence of immune-related adverse events was 58.2% and the incidence of grade 3/4 immune-related adverse events was 3.6%, and no treatment-related death was observed. The median PFS of the 55 patients was 5.0 (95%CI: 3.9-6.1) months, and the median OS was 11.4 (95%CI: 6.5-16.3) months. Univariate and multivariate analyses showed that liver function Child-Pugh scores and performance status ECOG score were the influencing factors of the objective response rate and survival. Conclusion In the real world anti-PD-1 antibody-based therapy is safe and effective in patients with advanced hepatocellular carcinoma, in which the performance status ECOG score and liver function Child-Pugh score before treatment are independent prognostic factors influencing survival.

A new form of familial platelet disorder caused by germline mutations in RUNX1 in a pedigree / 中华内科杂志

Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Clinical analysis of endoscopic esophageal dilation for the treatment of corrosive esophageal strictures in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical application of endoscopic esophageal dilation in the treatment of corrosive esophageal strictures in children.@*METHODS@#A retrospective analysis was performed on the clinical data of 15 children with corrosive esophageal strictures who underwent endoscopic esophageal dilation in Children's Hospital, Zhejiang University School of Medicine. The clinical features, treatment modality of endoscopic esophageal dilation, number of dilations, complications, and prognosis were reviewed.@*RESULTS@#A total of 96 esophageal dilations were performed in the 15 children with corrosive esophageal strictures, with a median of 6 dilations per child. Among them, 9 children (60%) underwent 6 or more dilations. The children with a stricture length of >3 cm had a significantly higher number of dilations than those with a stricture length of ≤3 cm (P<0.05). The children with strictures in a single segment had a significantly better treatment outcome than those with strictures in multiple segments (P=0.005). No complication was observed during all sessions of dilation. The overall effective rate (including significant improvement and improvement) of endoscopic esophageal dilation treatment was 87%, with 2 cases of failure.@*CONCLUSIONS@#Endoscopic esophageal dilation is an effective and relatively safe treatment method for corrosive esophageal strictures in children, and children with strictures in a single segment tend to have a better treatment outcome than those with strictures in multiple segments.

Exploration of discipline construction at university-affiliated hospitals in building " first-class universities and disciplines" / 中华医院管理杂志

Discipline construction is the core of hospital development. Under the initiative to build " first-class universities and disciplines" , in order to speed up the construction of first-class hospitals, a university-affiliated hospital carried out discipline construction management by optimizing top-level design, discipline differentiation development, evaluation index system construction and strengthening its application, and carrying out process management in the form of project system.In 2018, the hospital levelled its individual disciplines as leading ones, advantageous ones, backbone ones, backbone promising ones and potential ones, each granted with corresponding funding support. Medians of the disciplinary construction scoring of disciplines at various levels from 2015 to 2018 were used as the standard scoring in examinations in the next two years(2019 and 2020), guiding the disciplines to upgrade their design for discipline construction index system. The appraisal of discipline construction in 2019 and 2020 found 38 disciplines up to the standard scoring, including 16 twice higher than the scoring, while only 7 scored lower than the standard one. The hospital has made stage-based progress in discipline reputation, faculty, science research and social contribution, initially achieving effective guidance of disciplines of the hospital.

In vitro antibacterial activity of pediatric Faropenem sodium against respiratory tract pathogens in children / 中华实用儿科临床杂志

Objective:To evaluate the antibacterial activity of pediatric Faropenem sodium against common pathogens isolated from children′s respiratory tract in vitro, and to provide reference for its clinical research and application. Methods:Retrospective analysis.The minimum inhibitory concentration (MIC) of Faropenem sodium, Merope-nem, Imipenem and other antibiotics was determined by the agar dilution method.A total of 156 strains of Streptococcus pneumoniae [including 32 strains of Penicillin-susceptible Streptococcus pneumoniae (PSSP), 28 strains of Penicillin-intermediate Streptococcus pneumoniae (PISP) and 96 strains of Penicillin-resistant Streptococcus pneumoniae (PRSP)], 98 strains of Haemophilus influenza, 173 strains of Klebsiella pneumoniae, and 55 strains of Moraxella catarrhali clinical isolates were used.MIC 50, MIC 90 and the accumulative inhibition of the bacteria were investigated. Results:The MIC of Faropenem sodium against all the Streptococcus pneumoniae strains ranged from 0.010-2.000 mg/L.There was no difference in the MIC distribution of Faropenem sodium against PSSP, PISP and PRSP, and the MIC 90 value was all 1.000 mg/L.Faropenem sodium inhibited all the Haemophilus influenza strains at concentrations ranging from 0.030-8.000 mg/L.There was no difference in the MIC distribution of Faropenem sodium against Haemophilus influenza with or without β-lactamase and Ampicillin resistance.The MIC 90 value was all 4.000 mg/L.Ho-wever, the MIC of Faropenem sodium against Klebsiella pneumoniae ranged from 0.250 to above 32.000 mg/L, and both MIC 50 and MIC 90 were greater than 32.000 mg/L.Faropenem sodium inhibited all the Moraxella catarrhalis strains at concentrations ranging from 0.030-2.000 mg/L, with MIC 50 being 0.500 mg/L and MIC 90 being 1.000 mg/L. Conclusions:Antimicrobial susceptibility testing results in vitro demonstrate that pediatric Faropenem sodium has satisfactory antibacterial activities against Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis, but comparatively weak antibacterial activities against Klebsiella pneumoniae.