Correlation of early neurodevelopmental features of children with SYNGAP1 variants and their genotypes / 中华医学遗传学杂志

OBJECTIVE@#To explore the early neurodevelopmental features of young children with SYNGAP1 variants and their genotype-phenotype correlation.@*METHODS@#Young children with neurodevelopmental disorders (NDDs) (< 5 years old) who were referred to the Children's Hospital Affiliated to the Capital Institute of Pediatrics between January 2019 and July 2022 were selected as the study subjects. All children had undergone whole-exome sequencing, comprehensive pediatric neuropsychological assessment, familial segregation analysis, and pathogenicity classification. Meanwhile, young Chinese NDD children (< 5 years old) with pathogenic/likely pathogenic SYNGAP1 variants were retrieved from the literature, with information including detailed clinical and genetic testing, neurodevelopmental quotient (DQ) of the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). Children who did not have a detailed DQ but had their developmental status assessed by a medical professional were also included. The correlation between neurodevelopmental severity, comorbidity and SYNGAP1 variants were summarized.@*RESULTS@#Four young NDD children carrying SYNGAP1 variants were recruited (1 male and 3 females, with a mean age of 34.0 ± 18.2 months), among whom one harboring a novel variant (c.437C>G, p.S146*). Combined with 19 similar cases retrieved from the literature, 23 Chinese NDD young children were included in our study (8 males and 10 females, 5 with unknown sex, with a mean age of 37.1 ± 14.2 months). A loss of function (LOF) variant was found in 19 (82.6%) children. All of the children had presented global developmental delay (GDD) before the age of two. In addition, 16 (69.6%) had seizure/epilepsy at the age of 27.0 ± 12.1 months, among whom 15 had occurred independent of the global developmental delay. Myoclonic and absence were common types of seizures. Compared with those with variants of exons 8 to 15, the severity of developmental delay was milder among children with variants in exons 1 to 5.@*CONCLUSION@#The early neurodevelopment features of the SYNGAP1 variants for young children (< 5 years old) have included global developmental delay and seizure/epilepsy. All of the children may present GDD before the age of two. The severity of developmental delay may be related to the type and location of the SYNGAP1 variants.

Water stress memory in wheat/maize intercropping regulated photosynthetic and antioxidative responses under rainfed conditions.

Drought is a most prevalent environmental stress affecting the productivity of rainfed wheat and maize in the semiarid Loess Plateau of China. Sustainable agricultural practices such as intercropping are important for enhancing crop performance in terms of better physiological and biochemical characteristics under drought conditions. Enzymatic and non-enzymatic antioxidant enzyme activities are associated with improved abiotic tolerance in crop plants, however, its molecular mechanism remains obscure. A 2-year field study was conducted to evaluate the influence of intercropping treatment viz. wheat mono-crop (WMC), maize mono-crop (MMC), intercropping maize (IM) and wheat (IW) crops, and nitrogen (N) application rates viz. control and full-dose of N (basal application at 150 and 235 kg ha-1 for wheat and maize, respectively) on chlorophyll fluorescence, gas exchange traits, lipid peroxidation, antioxidative properties and expression patterns of six tolerance genes in both crops under rainfed conditions. As compared with their respective monocropping treatments, IW and IM increased the Fo/Fm by 18.35 and 14.33%, PS-11 efficiency by 7.90 and 13.44%, photosynthesis by 14.31 and 23.97%, C-capacity by 32.05 and 12.92%, and stomatal conductance by 41.40 and 89.95% under without- and with-N application, respectively. The reductions in instantaneous- and intrinsic-water use efficiency and MDA content in the range of 8.76-26.30% were recorded for IW and IM treatments compared with WMC and MMC, respectively. Compared with the WMC and MMC, IW and IM also triggered better antioxidant activities under both N rates. Moreover, we also noted that intercropping and N addition regulated the transcript levels of six genes encoding non-enzymatic antioxidants cycle enzymes. The better performance of intercropping treatments i.e., IW and IM were also associated with improved osmolytes accumulation under rainfed conditions. As compared with control, N addition significantly improved the chlorophyll fluorescence, gas exchange traits, lipid peroxidation, and antioxidant enzyme activities under all intercropping treatments. Our results increase our understanding of the physiological, biochemical, and molecular mechanisms of intercropping-induced water stress tolerance in wheat and maize crops.

Development of the index system of the quality evaluation standard for pharmacist training in cough and wheeze pharmaceutical care outpatient department / 中国药房

OBJECTIVE To establish the index system of quality evaluation standard for pharmacist training in cough and wheeze pharmaceutical care （CWPC） outpatient department， and to provide a basis for the selection of CWPC pharmacist training teachers and the improvement of training plans. METHODS Based on Kirkpatrick model， using the Delphi method， a total of 15 experts from 13 tertiary hospitals in 10 provinces in China were consulted to establish the standard index system of the quality evaluation for CWPC pharmacists training. Analytic hierarchy process （AHP） was adopted to determine the weights of each indicator and quantify the index system according to the weights of indicators at all levels. RESULTS The coefficient of expert authority was 0.810， the judgment coefficient was 0.727， and the familiarity coefficient was 0.893. The Kendall coordination coefficient of each index was 0.308-0.687. The P values of χ2 test were all less than 0.05， which indicated that the degree of coordination of the experts was high. After two rounds of correspondence， Kirkpatrick model-based index system of quality evaluation standard for CWPC pharmacist training was determined. The index system included 4 first-level indexes （participants’ reaction layer， learning gain layer， behavior improvement layer， training outcome layer）， 12 second-level indexes （such as training needs， teaching methods， theoretical knowledge， practical skills， job abilities， patient benefits， etc.） and 44 third-level indexes （such as clear training objectives， core system of CWPC， special device operation and evaluation， professional knowledge related to the treatment of cough and wheeze patients， promoting the construction of CWPC， improving patient compliance）. CONCLUSIONS The constructed index system of quality evaluation standard for CWPC pharmacist training has a certain level of authority and scientificity， and provides a scientific theoretical basis for quality evaluation of CWPC pharmacist training.

Efficacy evaluation of cluster nursing in robot-assisted surgery for the treatment of reducible atlantoaxial dislocation / 中华创伤杂志

Objective:To explore the effect of cluster nursing in robot-assisted surgery for the treatment of reducible atlantoaxial dislocation.Methods:A retrospective cohort study was conducted to analyze the clinical data of 41 patients with reducible atlantoaxial dislocation treated by robot-assisted surgery in Honghui Hospital affiliated to Xi′an Jiaotong University from January 2019 to December 2021, including 28 males and 13 females; aged 18-79 years [(45.2±10.3)years]. Ninteen patients received cluster nursing (cluster nursing group), with operating room nursing team set up on the basis of routine nursing and performed cluster nursing in line with evidence-based medicine. Twenty-two patients received routine nursing (routine nursing group). The operation time, intraoperative blood loss, frequency of intraoperative C-arm fluoroscopy, time of drainage tube placement and chief surgeon′s satisfaction for nursing were compared between the two groups. The degree of pain was evaluated by pain numerical score (NRS) at 12 hours, 24 hours, 48 hours, 72 hours, 1 month and 3 months after operation and at the last follow-up. The neck disability index (NDI) was assessed at 1 day before operation, 1 month after operation, 3 months after operation and at the last follow-up. The complications were observed.Results:All patients were followed up for 12-18 months [(16.7±3.7)months]. The operation time, intraoperative blood loss, frequency of C-arm fluoroscopy and time of drainage tube placement in cluster nursing group were (82.9±10.4)minutes, (105.9±11.8)ml, (3.8±0.6)times and (1.5±0.4)days, while those in routine nursing group were (125.7±12.8)minutes, (208.4±13.8)ml, (9.7±2.3)times and (3.6±0.6)days, respectively (all P<0.01). The chief surgeon′s satisfaction for nursing was 94.7% (18/19) in cluster nursing group and was 68.2% (15/22) in routine nursing group ( P<0.05). The NRS in cluster nursing group was (6.2±0.4)points, (6.0±0.7)points, (4.9±1.1)points, (2.7±0.5)points, (1.9±0.4)points, (1.8±0.4)points and (1.5±0.3)points at 12 hours, 24 hours, 48 hours, 72 hours, 1 month and 3 months after operation and at the last follow-up, while it was (7.6±0.6)points, (6.8±1.2)points, (5.8±1.5)points, (4.2±0.8)points, (3.4±0.7)points, (2.6±0.5)points and (2.2±0.5)points in routine nursing group ( P<0.05 or 0.01). There was no significant difference in the NDI between the two groups at 1 day before operation, but the NDI in cluster nursing group was 20.6±4.5, 14.6±2.8 and 10.7±2.5 at 1 month and 3 months after operation and at the last follow-up, while it was 26.9±4.1, 18.7±3.3 and 13.7±1.7 in routine nursing group (all P<0.01). There was no hematoma, infection or implant-related complications in both groups .Conclusion:For robot-assisted surgery in the treatment of reducible atlantoaxial dislocation, cluster nursing is associated with shortened operation time and time of drainage tube placement, decreased intraoperative blood loss and frequency of intraoperative fluoroscopy, increased chief surgeon′s satisfaction for nursing, reduced pain and accelerated functional recovery.

Effect of Qiling Baitouweng Tang on Proliferation and Apoptosis in Diffuse Large B-cell Lymphoma Through JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Qiling Baitouweng Tang （QLBTWT） on proliferation and apoptosis， Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway and interleukin-10 （IL-10） in diffuse large B-cell lymphoma （DLBCL）. MethodWith human DLBCL cells OCI-LY10 and U2932 as research objects， cell proliferation was detected by cell counting kit-8 （CCK-8） assay. After treatment with 0， 4.6， 9.3， 18.7， 37.5， 75， 150 mg·L-1 QLBTWT for 24 h， the half-inhibitory concentration （IC50） of OCL-LY10 and U2932 cells was calculated to be 9.33， 16.13 mg·L-1， respectively， based on which， 9.5， 19， 38 mg·L-1 QLBTWT were selected for subsequent experiments. After 0， 9.5， 19， 38 mg·L-1 QLBTWT treatment for 24 h， the zymogen activities of Caspase-3， Caspase-8 and Caspase-9 in OCI-LY10 and U2932 cells were detected using corresponding activity assay kits （colorimetric）， and the IL-10 expression was detected by enzyme-linked immuno sorbent assay （ELISA）. The apoptosis rate and cell cycle of OCI-LY10 and U2932 cells treated with different concentrations of QLBTWT for 24 h were detected by flow cytometry. The expressions of apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved poly adenosine diphosphate ribose polymerase （cleaved PARP）， cleaved Caspase-3］， JAK2， STAT3， phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3） pathway proteins， and c-Myc protein in OCL-LY10 and U2932 cells after 24 h treatment with 0， 9.5， 19， 38 mg·L-1 QLBTWT were all tested by Western blot. ResultAfter QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， cell proliferation was inhibited in each QLBTWT group compared with that in the control group （P<0.05， P<0.01）. The zymogens of Caspase-3， Caspase-8 and Caspase-9 were activated （P<0.01）， and there was an increase in cell apoptosis （P<0.05， P<0.01） and cell cycle arrest at Gap phase1 （G1） phase in 9.5， 19 and 38 mg·L-1 QLBTWT group （P<0.05， P<0.01）. After 9.5， 19 and 38 mg·L-1 QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， the expressions of Bcl-2， p-JAK2 and p-STAT3 proteins were decreased （P<0.01）， and the expressions of Bax， cleaved PARP and cleaved Caspase-3 proteins were increased （P<0.01）， but no significant change was observed in the expressions of JAK2 and STAT3 proteins. Compared with the conditions in the control group， the expressions of c-Myc， p-JAK2， and p-STAT3 proteins were down-regulated in 19 mg·L-1 QLBTWT group and 19 mg·L-1 QLBTWT+10 μg·L-1 IL-10 group （P<0.05， P<0.01）， and up-regulated in 10 μg·L-1 IL-10 group （P<0.05， P<0.01）， while there was no difference in JAK2/STAT3 proteins. ConclusionQLBTWT can inhibit proliferation and induce apoptosis of human DLBCL cells OCI-LY10 and U2932， and the potential mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.

Analysis of the characteristics of SPTB gene variants among 16 children with Hereditary spherocytosis / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation.@*METHODS@#Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test.@*RESULTS@#The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.@*CONCLUSION@#Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.

Concurrent Tuberculous Meningoencephalitis and Anti-NMDAR Encephalitis: A Case Report.

Background: Cases of tuberculosis triggering the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are absent. Case Presentation: Herein, we report, for the first time, the case of a patient who developed anti-NMDAR encephalitis likely due to tuberculosis. The patient, a 33-year-old man, experienced weight loss during the previous 2 years, along with acute headache, fever, cognitive deficits, and right ophthalmoplegia. Based on these findings and on data from magnetic resonance imaging and cerebrospinal fluid antibody analysis, tuberculous meningoencephalitis combined with anti-NMDAR encephalitis was diagnosed. Marked clinical and brain imaging improvement were observed after antituberculosis and high-dose corticosteroid treatment initiation, which persisted during the 3 months of follow-up. Conclusions: This case suggests that anti-NMDAR encephalitis may arise after tuberculosis infection. Therefore, clinicians must be aware of this possibility, especially when cognitive and new neurological symptoms suddenly occur.

Does serum progesterone level impact the ongoing pregnancy rate in frozen embryo transfer under artificial preparation with vaginal progesterone? Study protocol for a randomized controlled trial.

BACKGROUND: In previous retrospective studies, low serum progesterone level on the embryo transfer day is associated with lower clinical pregnancy and ongoing pregnancy rates. Whether adding progesterone in low serum progesterone patients can rescue the outcome, there is no sufficient evidence from randomized controlled studies. METHODS: This trial is a clinical randomized controlled study (high serum progesterone vs low serum progesterone 1:1, 1:1 randomization ratio of intervention vs the control group with low serum progesterone). The eligible hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles, will be recruited and randomly assigned to two parallel groups when serum progesterone is < 7.24µg/l on the day of embryo transfer for D3. The intervention group will be extrally given intramuscular progesterone 40 mg per day from D3 to 8 weeks of gestation if clinical pregnancy. The primary outcome is the ongoing pregnancy (beyond 12 weeks of gestation) rate. DISCUSSION: The findings of this study will provide strong evidence for whether the progesterone addition from the D3 in low serum progesterone patients can improve the outcome in the HRT-FET cycle. TRIAL REGISTRATION: ClinicalTrials.gov NCT04248309 . Registered on January 28, 2020.

Analysis of pathogen detection results of neonatal Echovirus 11 infection outbreaks in Guangdong Province in 2019 / 中华微生物学和免疫学杂志

Objective:To analyze the laboratory test results of two outbreaks of neonatal enterovirus infections in Guangdong Province in 2019 and the genetic characteristics of Echo11, aiming to provide reference for the prevention and control of neonatal enterovirus infections.Methods:The pathogenic specimens of neonatal cases suspected of enterovirus infection were collected. Fluorescence quantitative PCR and sequencing were used for enterovirus typing and identification, and virus isolation was carried out for positive specimens.The complete sequences of VP1 of Echo11 were amplified and sequenced and the phylogenetic analysis was performed using the bioinformatics software such as Danstar6, Bioedit7.09 and MEGA6.06.Results:A total of 93 specimens from 36 neonatal cases were collected. After identification, 55 specimens from 24 cases were positive for enterovirus, of which 23 cases were positive for Echo11 and one case was positive for Coxsackievirus B4(CVB4). A total of 29 enterovirus strains were isolated from the specimens of 19 cases, of which 28 were Echo11 from 18 cases, and one was CVB4. Phylogenetic analysis revealed that the nucleotide homology between the 18 strains of Echo11 in this study was 98.2%-100.0%, and the nucleotide homology between the Echo11 strains causing the two neonatal infections was 99.7%-100.0% and 99.8%-100.0%, respectively. Echo11 could be divided into six genotypes as A, B, C, D, E and F, in which genotype A and genotype C were further divided into A1-5 and C1-4, and genotype D could be divided into D1-5. The 18 strains of Echo11 in this study were all subtype D5.Conclusions:In 2019, two outbreaks of neonatal infections in medical institutions in Guangdong Province were caused by Echo11, which belonged to the genotype D5.

Standards for the interpretation of constitutional copy number gain: Recommendation from the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource (ClinGen) / 中华医学遗传学杂志

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.

Summary of best evidence for emergency target blood pressure management of acute aortic dissection / 中国实用护理杂志

Objective:To evaluate and summary the relevant evidence of emergency target blood pressure management in acute aortic dissection, so as to provide guidance for the evidence-based practice of emergency target blood pressure management.Methods:According to the "6S" evidence pyramid model, the evidence about emergency target blood pressure management of acute aortic dissection in various databases and professional association websites at home and abroad was retrieved, including clinical decision, guidelines, expert consensus, systematic evaluation, randomized controlled trial, cohort study, case series, etc. Two researchers used corresponding literature quality evaluation tools to evaluate the quality of the included literature, extracted and summarized the evidence of the literature above grade B.Results:A total of 22 articles were included in this study, including 6 clinical decisions, 5 guidelines, 7 expert consensus, 1 systematic evaluation, 1 randomized controlled trial, 1 cohort study and 1 case series, forming 37 best evidences, including 9 topics such as target value setting, management strategies, disease observation, medical history collection, monitoring methods, vasoactive drugs, non vasoactive drugs, auxiliary examination, health education.Conclusions:The summarized best evidence provides a reference for emergency medical staff to manage the emergency target blood pressure of acute aortic dissection. It is recommended that emergency medical staff follow the summarized best evidence to formulate an individualized target blood pressure management scheme for patients.

Effect of Pulsatilla Saponin A on Proliferation and Apoptosis of Burkitt Lymphoma Cells Based on JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of pulsatilla saponin A （PSA） on proliferation and apoptosis of human Burkitt lymphoma （BL） cell line Raji cells and expression of related pathway proteins. MethodWith Raji cells as the research object， the cell proliferation was detected by cell counting kit-8 （CCK-8） method， and the half-maximal inhibitory concentration （IC50） values of 24 h， 48 h and 72 h were calculated to be 19.77， 18.31， 16.70 μmol·L-1， respectively. In subsequent related experiments， 0， 8， 16， 32 μmol·L-1 PSA were selected according to the IC50 value of Raji cells treated with PAS for 72 h. After 0， 8， 16， 32 μmol·L-1 PSA acted on Raji cells for 24， 48， 72 h， the optical density values of cell growth curve were detected by CCK-8 method. The zymogen activities of cysteine aspartate-specific protease （Caspase）-3， Caspase-8 and Caspase-9 in Raji cells treated with 0， 8， 16 and 32 μmol·L-1 PSA for 24 h were measured by Caspase-3， Caspase-8 and Caspase-9 colorimetric assay kit. The apoptosis rate and cell cycle of Raji cells treated with different concentrations of PSA after 24 h were detected by flow cytometry. The expression of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved poly（ADP-ribose） polymerase （cleaved PARP）， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3） apoptosis related protein and Janus kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3）， phosphorylated-JAK2 （p-JAK2）， and phosphorylated- STAT3 （p-STAT3） pathway proteins in Raji cells after 24 h of treatment with 0， 8， 16 and 32 μmol·L-1 PSA were tested by Western blot. ResultCompared with control group， decreased cell survival rate， inhibited cell proliferation， activated zymogens of Caspase-3， Caspase-8 and Caspase-9 （P<0.01）， increased apoptosis （P<0.05， P<0.01）， and enhanced cell cycle arrest in Gap phase 2 （G2） were observed in 8， 16 and 32 μmol·L-1 PSA groups（P<0.05， P<0.01）. Compared with control group， cells treated with 8， 16 and 32 μmol·L-1 PSA had lower expression of Bcl-2， p-JAK2， p-STAT3 proteins （P<0.05， P<0.01）， and higher expression of Bax， cleaved PARP and cleaved Caspase-3 protein （P<0.01）， while no significant change was found in the expression of JAK2 and STAT3 proteins. ConclusionPSA could inhibit proliferation and induce apoptosis of Raji cells， and its potential mechanism might be related to the regulation of JAK2/STAT3 signaling pathway.

Text Analysis of Enterprise Social Responsibility Report of Pharmaceutic al Industry in China ：Taking Listed Com- panies as an Example / 中国药房

OBJECTIVE：To provide reference for pharmaceutical enterprises to better fulfill their social responsibilities . METHODS：Taking the pharmaceutical enterprises listed in Shanghai and Shenzhen stock markets as the research objects ，the social responsibility texts and environmental protection texts of the included enterprises from 2017 to 2019 were classified and analyzed according to the three dimensions of time ，ownership and drug production type by using ROST Content Mining 6.0 software. The semantic network and node centrality were analyzed. RESULTS ：From the social responsibility texts of the included enterprises，it could be seen that from the perspective of time dimension ，the included enterprises paid more attention to “employees”，“social responsibility ”and“development”in 2017-2019，and the high-frequency words in the three years were relatively stable. From the perspective of ownership ，state-owned holding enterprises paid more attention to “development”and “targeted poverty reduction ”，while private holding enterprises paid more attention to “employees”，and collective holding enterprises paid more attention to “social responsibility ”. From the perspective of drug production type ，the word frequency of “targeted poverty reduction ”of TCM pharmaceutical enterprises was higher. From the environmental protection texts of the included enterprises，it could be seen that from the time dimension ，the included enterprises paid more and more attention to environmental protection in recent years ，and the description of environmental protection in the texts was more detailed. From the perspective of ownership，private holding enterprises paid more attention to environmental protection than collective holding enterprises and state-owned enterprises. From the perspective of drug production type ，due to the different types of drugs ，chemical drugs ，TCM， biological drugs and active pharmaceutical ingredients enterprises had their own characteristics in pollutants and their treatment processes. The results of semantic network and node centrality analysis showed that ，“development”，“protection” and “targeted poverty reduction ”were three high-frequency words with high centrality in the semantic analysis network of social responsibility text ，the middle centrality was 5.555，1.695，1.521 respectively；“emission”and“testing”were two key words with high centrality in the semantic analysis network of environmental protection texts ，the middle centrality was 3.856， 1.914 respectively，which further reflected that the included enterprises paid more attention to the above issues in terms of social responsibility performance and environmental protection. CONCLUSIONS ：The listed pharmaceutical enterprises have a broad consensus on social responsibility in China ，and have well fulfilled their social responsibility ，which is well combined with the current social hot spots. For environmental protection ，as a high pollution industry ，the pharmaceutical enterprises also performs the responsibility of environmental protection.

Mechanism of transcutaneous electrical acupoint stimulation in improving the symptoms and gastric accommodation in patients with functional dyspepsia / 中华消化杂志

Objective:To investigate the therapeutic efficacy and mechanisms of transcutaneous electrical acupoint stimulation (TEAS) in the treatment of postprandial distress syndrome (PDS) in functional dyspepsia (FD).Methods:A double-blinded, randomized, controlled study was conducted. At Sir Run Run Shaw Hospital, Medical School Zhejiang University 40 patients aged 18-70 years old who met the Rome Ⅳ diagnostic criteria of PDS were prospectively enrolled. After informed consent, the patients were randomly assigned to TEAS group or sham-TEAS group. The patients in the TEAS group received transcutaneous electrical acupoint stimulation at acupoints Zusanli and Neiguan, and those in the sham-TEAS group underwent stimulation at other mimic acupoints for four weeks. The symptoms, gastric accommodation (initial satiety volume (ISV) and maximum tolerable volume (MTV), time of half gastric emptying of solid food ( T1/2) and heart rate variability (high frequency, low frequency and ratio of low frequency to high frequency) were compared between the two groups before and after treatment. The expression levels of inflammatory cytokines in duodenal mucosa were also evaluated by polymerase chain reaction in PDS patients and 24 healthy volunteers. Independent sample t test, Mann-Whitney U test and chi square test were used for statistical analysis. Results:A total of 26 PDS patients were enrolled in the study, 13 cases each in the TEAS group and sham-TEAS group. Between the patients of the two groups, there were no statistically significant differences in gender, age, or score of 36-item short form health survey (SF-36), score of self-rating anxiety scale (SAS), score of self-rating depression scale (SDS), score of dyspeptic symptom severity index (DSSI), ISV, MTV, T1/2 or heart rate variability indexes (high frequency, low frequency and ratio of low frequency to high frequency) before treatment (all P>0.05). After treatment, the DSSI score of TEAS group was lower than that of sham-TEAS group (13.5±5.3 vs. 19.9±9.3), the values of ISV and MTV were both higher than those of sham-TEAS group ((180.0±44.6) mL vs. (121.9±61.0) mL, (480.4±200.7) mL vs. (338.5±108.8) mL), and the differences were all statistically significant ( t=2.18, 2.77 and 2.24, all P<0.05). After treatment there was no statistically significant difference in T1/2 between TEAS group and sham-TEAS group ( P>0.05). There was no statistically significant difference in T1/2 between before and after treatment in patients of TEAS group ( P>0.05). After treatment, the high frequency increased (5.3±1.2 vs. 4.0±0.9) and the ratio of low frequency to high frequency decreased (1.0±0.2 vs. 1.3±0.2), and the differences were statistically significant ( t=-3.31 and 3.73, both P<0.01). The expression levels of interleukin 6 (IL-6) mRNA in mucosa of duodenal bulb and descending duodenum of PDS patients were both higher than that of healthy control group (0.68, 0.11 to 6.74 vs. 0.03, 0.02 to 0.25; 6.46, 1.35 to 12.62 vs. 0.86, 0.32 to 2.90), and the differences were statistically significant ( Z=-2.24 and -2.03, P=0.02 and 0.04). After TEAS treatment for four weeks, the expression of IL-6 mRNA in duodenal bulb mucosa decreased compared with that before treatment in TEAS group (0.04, 0.01 to 0.06 vs. 0.23, 0.09 to 3.66) and the difference was statistically significant ( Z=-2.07, P=0.04). Conclusions:TEAS can improve the gastric accommodation and dyspeptic symptoms in PDS patients. The mechanism may be related with the vagal pathway mediating and regnlating the expression of inflammatory cytokine IL-6 in duodenal bulb mucosa.

Comparison of efficacy of systematic nursing in operating room and routine nursing in reducing intraoperative pressure injury in patients with spine fracture combined with spinal cord injury / 中华创伤杂志

Objective:To compare the effect of systematic nursing in operating room and routine nursing in reducing intraoperative stress injury in patients with spinal fracture and spinal cord injury.Methods:A retrospective case-control study was conducted to analyze the clinical data of 285 patients with cervical or thoracolumbar fracture associated with spinal cord injury admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2018 to December 2019, including 168 males and 127 females, with the age of 38-59 years [(47.8±8.5)years]. All patients underwent posterior decompression and fusion with internal fixation. Of all, 138 patients received systematic nursing in operating room including systematic evaluation and management before, during and after operation (observation group), and 147 patients received routine nursing including only intraoperative preventive care of pressure ulcer (control group). The incidence of pressure injury on the day after operation, degree of injury and location of injury at postoperative 3 days, and area of injury on the day after operation and at postoperative 3 days were compared between the two groups. The degree of injury was evaluated using the new stress injury staging assessment published by the American National Pressure Ulcer Advisory Panel (NPUAP).Results:The incidence of pressure injury in observation group [5.1% (7/138)] was lower than that in control group [12.2% (18/147)] on the day after operation ( P<0.05). The incidence of stage I, stage II, and stage III pressure injury in observation group [2.9% (4/138), 2.2% (3/138), 0.0%] was also lower than that in control group [8.2% (12/147), 3.4% (5/147), 0.6% (1/147)] at postoperative 3 days ( P<0.05). There was no significant difference in the incidence of pressure injury in the knee, chest, face and anterior superior iliac spine between the two groups ( P>0.05). The total proportion of pressure injury in the face and anterior superior iliac spine was 71% (5/7) in observation group, showing no significant difference from that in control group [83% (15/18)] ( P>0.05). The area of injury was (3.2±1.2)cm 2 and (3.2±1.1)cm 2 in observation group on the day after operation and at postoperative 3 days, lower than that in in control group [(5.1±1.5)cm 2 and (5.1±1.4)cm 2] ( P<0.01). Conclusion:Compared with the routine nursing, systematic nursing in operating room can significantly reduce the incidence, degree and area of intraoperative pressure injury in patients with spinal fracture accompanied by spinal cord injury, and deserves clinical promotion.

A Clinical Randomized Controlled Trial of Acupuncture Treatment of Gastroparesis Using Different Acupoints.

Objective: To explore the effect of "selecting acupoints by site" on the synergy effect of "acupoint compatibility" according to the clinical efficacy of acupuncture treatment of patients with gastroparesis. Methods: A total of 99 patients who met the diagnostic criteria for gastroparesis were enrolled in 3 clinical centers and randomly divided into group A (33 cases), group B (33 cases, 1 case of shedding), and group C (33 cases, 1 case of shedding). In group A, acupuncture was performed at Zhongwan (CV 12) and Zusanli (ST 36); in group B, acupuncture was performed at Neiguan (PC 6) and Zusanli (ST 36); in group C, acupuncture was performed at nonacupoint and Zusanli (ST 36). Treatment was performed for 30 minutes every day, 5 days as a course of treatment. There were 2 days off between courses and three courses in total. Differences in a main symptom index of gastroparesis (GCSI) scores, 9 symptom scores, and a health questionnaire (SF-36) were compared between each group before and after treatment and 4 weeks after the end of treatment. The difference of gastric emptying rate was compared before and after treatment. Results: The GCSI scores of each group after treatment and at follow-up were significantly lower than those before treatment (P < 0.01), and the reduction in group A was greater than that of groups B and C (P < 0.01). The score of each symptom was meaningfully lower than that before treatment (P < 0.01 or P < 0.05). The effect was best in group A, followed by group B. After treatment, the barium meal in the stomach of the three groups was significantly reduced compared with before treatment (P < 0.01). There was no statistical difference between the groups. The results of SF-36 showed that acupuncture treatment can improve health status, to a certain extent, and there was no significant difference in the three groups. Conclusion: (1) Acupuncture is an effective method for the treatment of gastroparesis. (2) The combination of Zhongwan (CV 12) with Zusanli (ST 36) showed the most promising effect on relief of the symptoms in patients with gastroparesis. (3) "Selecting acupoints by site" is the key factor affecting the synergy effect of "acupoint compatibility." This trial was registered with the International Center for Clinical Trials (registration no. NCT02594397).

Meta-analysis of the Effectiveness of Inhaled Corticosteroids Combined with Tiotropium Bromide versus Inhaled Corticosteroids Alone in the Treatment of Asthmatic-COPD Overlap Syndrome / 中国药房

OBJECTIVE：To systematically e valuate the effectiveness of inhaled corticosteroids combined with tiotropium bromide versus inhaled corticosteroids alone in the treatment of asthmatic-COPD overlap syndrome ，and to provide evidence-based reference for clinical use. METHODS ：Retrieved from PubMed ，Web of Science ，Embase，Cochrane Library ，CBM，CNKI， VIP，Wanfang database ，during the establishment of the database to Nov. 2019，randomized controlled trials （RCT）about inhaled corticosteroids combined with tiotropium bromide （trial group ）versus inhaled corticosteroids alone （control group ）in the treatment of asthmatic-COPD overlap syndrome were collected. After data extraction of included literatures met inclusion criteria ，quality evaluation with modified Jadad scale ，Meta-analysis was performed for response rate ，forced expiratory volume in the first second （FEV1），forced vital capacity （FVC），FEV1/FVC，inspiratory fraction （IC/TLC），residual to total ratio （RV/TLC），asthma symptom（ACT）score，chronic obstructive pulmonary symptom （CAT）score，the times of acute exacerbations by Rev Man 5.3.0 software. RESULTS ：A total of 25 RCTs were included ，involving 2 828 patients. The results of Meta-analysis showed that the response rate [RR ＝1.16，95％CI（1.10，1.22），P＜0.001]，FEV1[MD＝0.44，95％CI（0.35，0.54），P＜0.001]，FVC [MD ＝0.70， 95％CI（0.46，0.95），P＜0.001]，FEV1/FVC [MD= 8.79，95％CI（6.22，11.37），P＜0.001]，IC/TLC [MD ＝4.93，95％CI（3.01， 6.85），P＜0.001]，RV/TLC [MD ＝－9.22，95％CI（－9.79，－8.66），P＜0.001]，ACT score [MD ＝5.38，95％CI（4.30，6.47）， P＜0.001]，CAT score [MD ＝－3.67，95％CI（－4.89，－2.45），P＜0.001] and the times of acute exacerbations [MD ＝－1.49， 95％CI（－2.82，－0.17），P＝0.03] in trial group were significantly higher than control group ，with statistical significance. CONCLUSIONS：Compared with inhaled corticosteroids alone ，inhaled hormone combined with tiotropium bromide can improve the response rate and pulmonary function ，but increase the times of acute exacerbation of patients with asthmatic-COPD overlap syndrome.

The diagnostic and prognostic significance of long non-coding RNA CRNDE in pan-cancer based on TCGA, GEO and comprehensive meta-analysis.

BACKGROUND: Accumulating evidence has confirmed that CRNDE is significantly expressed in various cancers, suggesting that it may be a potential biomarker for cancer. However, its diagnostic and prognostic values of CRNDE in cancer are not completely clear. Therefore, we conduct a comprehensive study on CRNDE in cancer. MATERIALS AND METHODS: CRNDE expression data were downloaded from The Cancer Genome Atlas (TCGA). Microarray data were derived from the Gene Expression Omnibus (GEO) database to validate its differential expression. Furthermore, the receiver operator characteristic curve (ROC) and Kaplan-Meier survival analysis were used to evaluate the diagnostic and prognostic values of CRNDE in cancer, respectively. Finally, we carried out a meta-analysis to comprehensively evaluate the diagnostic and prognostic values of CRNDE in cancer. RESULTS: In TCGA database, CRNDE was overexpressed in nine types of cancer, among which polymorphic glioblastoma and colonic adenocarcinoma are the most highly expressed. The area under curves (AUC) of nine cancer types ranged from 0.855 to 0.984. Additionally, the high expression level of CRNDE was significantly associated with poor overall survival only in hepatocellular carcinoma (p = 0.032) among the nine cancers in the Kaplan-Meier survival analysis. Finally, the results of the meta-analysis on the literatures showed that the pooled sensitivity, specificity, summary receiver operator characteristic curve (SROC), and the overall hazard ratio of CRNDE in cancers were 0.77 (95% CI: 0.71-0.82), 0.90 (95% CI: 0.82-0.95), 0.87 (95% CI: 0.84-0.90), and 1.66 (95% CI: 1.37-2.01), respectively. CONCLUSION: CRNDE could be a potential biomarker for cancer diagnosis and prognosis.

The effect of butylphthalide on cell necroptosis in cerebral ischemia reperfusion injury model mice / 中华行为医学与脑科学杂志

Objective To explore the protective effect and mechanism of butylphthalide on cerebral ischemia reperfusion injury in mice.Methods The cerebral ischemia reperfusion injury model was established by middle cerebral ischemia occlusion (MCAO).Thirty mice were divided into sham group,ischemia reperfusion group(I/R group) and butylphthalide group (NBP group) with 10 in each group.Neurological defect score and brain infarction volume were detected by TTC to evaluate the treatment effects of butylphthalide.Western blot was used to detect expression of RIP,RIP3 and AIF.Immunocoprecipitation (IP) was used to detect the interaction of AIF and RIP3.Immunofluorescence(IF) was used to detect the nuclear translocation and co-localization of AIF and RIP3.Results Compared with the I/R group,NBP treatment reduced the neurological defect score (I/R:(2.60 ± 0.22),NBP:(1.90 ± 0.23),t =2.18,P＜ 0.05) and brain infarction volume(I/R:(38.32±2.22) ％,NBP:(25.23±2.70) ％,t=3.74,P＜0.01).I/R elevated the expression of RIP1 and RIP3 whereas NBP significantly inhibited the expression of these two proteins (RIP1 (I/R:0.99±0.24,NBP:0.47±0.10,t=2.71,P＜0.05);RIP3 (I/R:0.52±0.17,NBP:0.15±0.04,t=2.87,P＜0.05)).I/R and NBP had no significant effects on the expression of AIF,but the IP results showed that I/R increased the interaction between AIF and RIP3 compared with the sham group.NBP alleviated the interaction between AIF and RIP3.IF results showed that the colocalization and nuclear expression of AIF and RIP3 increased after I/R whereas NBP treatment decreased the effect induced by I/R.Conclusion Butylphthalide alleviated cerebral ischemia reperfusion injury in mice through inhibiting the cell necroptosis.The mechanisms may correlate with decreasing the expression of RIP1 and RIP3 and alleviating the interaction and nuclear translocation of AIF and RIP3.

Analysis of related factors for clinical characteristics and the outcome in centenarian hospitalized patients / 中华老年医学杂志

Objective To investigate the health status of centenarian hospitalized patients and analyze the risk factors for in-hospital death in Nanjing district.Methods All centenarians hospitalized patients who were discharged from wards of 10 upper first-class general hospitals in Nanjing district during the past five years were retrieved from their hospital information systems.Then,a retrospective study was performed on centenarians' data of general information,laboratory test results,Charlson comorbidity index (CCI),neutrophil to lymphocyte ratio (NLR) and shock index(SI),etc.were calculated and collected.Relevant risk factors for in-hospital death were analyzed by multivariate logistic regression analysis.Results A total of 156 patients aged 100 years and over,with an average age of (101.0±2.1)years,were enrolled during the past 5 years.The top 3 admitting diagnosis for the patients were pulmonary infection(30.1％,47/156 cases),coronary heart disease(10.9％,17/156 cases)and cerebrovascular disease(7.1％,11/156 cases).Fifty patients died during hospitalization,with a mortality of 32.1％ (50/156).Pneumonia was the most common admitting diagnosis(40.0％,20/50 case).Among causes of death,the combined admitting diagnosis with dementia,chronic renal insufficiency,one or more basic disease were significantly associated with death.There were statistically significant differences between bad vs.good vs.indifferent prognosis in heart rate,shock index,leukocyte count,neutrophil count,NLR,hemoglobin,albumin,albumin/globulin,fasting blood glucose,blood urea nitrogen,serum creatinine,C-reactive protein(CRP)and CCI levels.Multivariate logistic regression analysis suggested that NLR≥13.18,fasting blood glucose ≥7.56 mmol/L,blood urea nitrogen ≥20.74 mmol/L,CRP≥65 mg/L and CCI≥3 might be predictors for in-hospital death in the cohort(OR =48.91、3.43、1.22、6.55、1.55,all P＜0.05).Conclusions Pulmonary infection is the most common reason for admission and the cause of death in centenarian inpatients.Comorbidities increase the risk of death.To lower in-hospital mortality,CCI and other assessment indicators should be used to strengthen the comprehensive assessment and chronic disease management of hospitalized centenarians.Infectious diseases should be prevented beforehand.