ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology， animal experiments， and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 （CCK-8） assay was adopted to observe the effects of different volume fractions （5%， 10%， 15%， and 20%） of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells， and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma （5%， 10%， 15%， and 20%） on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-， medium-， and high-dose （4.63， 9.25， 18.5 g·kg^-1） Huangqi Xiayuxue decoction and sorafenib （20 mg·kg^-1） groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention， hematoxylin-eosin （HE） staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay was employed to detect cell apoptosis. Immunohistochemistry （IHC） was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 （PI3K/Akt/FoxO1） signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology， among which tumor protein p53 （TP53）， Akt1， and signal transducer and activator of transcription 3 （STAT3） were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation， as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group， all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells （P<0.01）. The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma （P<0.01）. Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume， promoted tumor cell apoptosis in the high-dose group， up-regulated the protein and mRNA levels of Bax and Caspase-3， down-regulated the protein and mRNA levels of Bcl-2， and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway （P<0.05， P<0.01）. ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.

ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology， animal experiments， and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 （CCK-8） assay was adopted to observe the effects of different volume fractions （5%， 10%， 15%， and 20%） of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells， and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma （5%， 10%， 15%， and 20%） on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-， medium-， and high-dose （4.63， 9.25， 18.5 g·kg^-1） Huangqi Xiayuxue decoction and sorafenib （20 mg·kg^-1） groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention， hematoxylin-eosin （HE） staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay was employed to detect cell apoptosis. Immunohistochemistry （IHC） was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 （PI3K/Akt/FoxO1） signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology， among which tumor protein p53 （TP53）， Akt1， and signal transducer and activator of transcription 3 （STAT3） were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation， as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group， all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells （P<0.01）. The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma （P<0.01）. Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume， promoted tumor cell apoptosis in the high-dose group， up-regulated the protein and mRNA levels of Bax and Caspase-3， down-regulated the protein and mRNA levels of Bcl-2， and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway （P<0.05， P<0.01）. ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.

Objective:To evaluate the new model of group screening combined with opportunistic screening for the diagnosis and treatment of gastric cancer.Methods:Group screening combined with opportunistic screening was used for gastric cancer screening. (1) Group screening. Cluster sampling was used to screen gastric cancer by endoscopy in high-risk population (aged 40-<70 years) of rural residents in Weihai from July 2017 to December 2020, and biopsy was obtained for histopathology if necessary. Main collection parameters included the detection rate of advanced gastric cancer, early gastric cancer and high-grade intraepithelial neoplasia (HGIN). (2) Opportunistic screening. The changes of the detection rates of early gastric cancer in opportunistic screening in 2 hospitals in Weihai area were observed during the same period of time.Results:(1) In group screening, from July 2017 to December 2020, the first batch of 8 000 cases of gastric cancer screening were completed. The cases of advanced gastric cancer, early gastric cancer and HGIN were 36, 28, and 62, respectively. The detection rates of gastric cancer and early gastric cancer were 0.80% (64/8 000) and 43.75% (28/64), respectively. The proportion of early gastric cancer+HGIN who received endoscopic submucosal dissection (ESD) was 77.78% (70/90), and the rate of curative resection was 100.00%(70/70). (2) Opportunistic screening: from July 2017 to December 2020, the annual early gastric cancer detection rates in opportunistic screening in Wendeng District Traditional Chinese and Western Medicine Hospital were 16.67% (1/6), 20.00% (3/15), 23.53% (4/17), and 33.33% (6/18) in the consecutive 4 years, respectively. The annual detection rates of early gastric cancer in opportunistic screening in Ru Shan Peoples Hospital were 14.74% (14/95), 23.80% (60/252), 25.49% (65/255), and 24.04% (50/208), respectively. The detection rates of opportunistic screening for early gastric cancer in hospitals in Weihai city increased year by year.Conclusion:In areas with high incidence of gastric cancer, a certain scale of group screening can lead to a wider range of opportunistic screening, resulting in the increase of the detection rate of early gastric cancer. The new model of diagnosis and treatment of gastric cancer is worth recommendation.

Objective::Cardiac damage is commonly reported in patients with coronavirus disease 2019 (COVID-19) but its prevalence and impact on the long-term survival of patients remain uncertain. This study aimed to explore the prevalence of myocardial injury and assess its prognostic value in patients with COVID-19.Methods::A single-center, retrospective cohort study was performed at the Affiliated Hospital of Jianghan University. Data from 766 patients with confirmed COVID-19 who were hospitalized from December 27, 2019 to April 25, 2020 were collected. Demographic, clinical, laboratory, electrocardiogram, treatment data and all-cause mortality during follow-up were collected and analyzed.Results::Of the 766 patients with moderate to critically ill COVID-19, 86 (11.2%) died after a mean follow-up of 72.8 days. Myocardial injury occurred in 94 (12.3%) patients. The mortality rate was 64.9% (61/94) and 3.7% (25/672) in patients with and without myocardial injury, respectively. Cox regression showed that myocardial injury was an independent risk factor for mortality (hazard ratio: 8.76, 95% confidence interval: 4.76-16.11, P < 0.001). Of the 90 patients with myocardial injury with electrocardiogram results, sinus tachycardia was present in 29, bundle branch block in 26, low voltage in 10, and abnormal T-wave in 53. Conclusions::COVID-19 not only involves pneumonia but also cardiac damage. Myocardial injury is a common complication and an independent risk factor for mortality in COVID-19 patients.

Objective::Cardiac damage is commonly reported in patients with coronavirus disease 2019 (COVID-19) but its prevalence and impact on the long-term survival of patients remain uncertain. This study aimed to explore the prevalence of myocardial injury and assess its prognostic value in patients with COVID-19.Methods::A single-center, retrospective cohort study was performed at the Affiliated Hospital of Jianghan University. Data from 766 patients with confirmed COVID-19 who were hospitalized from December 27, 2019 to April 25, 2020 were collected. Demographic, clinical, laboratory, electrocardiogram, treatment data and all-cause mortality during follow-up were collected and analyzed.Results::Of the 766 patients with moderate to critically ill COVID-19, 86 (11.2%) died after a mean follow-up of 72.8 days. Myocardial injury occurred in 94 (12.3%) patients. The mortality rate was 64.9% (61/94) and 3.7% (25/672) in patients with and without myocardial injury, respectively. Cox regression showed that myocardial injury was an independent risk factor for mortality (hazard ratio: 8.76, 95% confidence interval: 4.76-16.11, P < 0.001). Of the 90 patients with myocardial injury with electrocardiogram results, sinus tachycardia was present in 29, bundle branch block in 26, low voltage in 10, and abnormal T-wave in 53. Conclusions::COVID-19 not only involves pneumonia but also cardiac damage. Myocardial injury is a common complication and an independent risk factor for mortality in COVID-19 patients.

Objective:To investigate the coverage rate and the adverse reactions of National Immunization Program vaccines in children with spinal muscular atrophy (SMA).Methods:A cross-sectional retrospective cohort study was carried out from July 2016 to June 2019, 192 children (116 boys and 76 girls) with SMA registered by Capital Institute of Pediatrics and 191 healthy children (115 boys and 76 girls) vaccinated in Chaoyang Olympic Village Community Health Service Center from July 2016 to December 2018 were included. Questionnaire survey was designed to investigate the vaccination coverage rate and associated adverse events. The t-test and χ 2 test were used to compare the difference between SMA patients and healthy children. Results:The coverage rate of age-appropriate immunization in SMA children was 62.0% (119/192) in general, and were 52.2% (12/23), 55.7% (68/122), and 83.0% (39/47) for SMA type 1-3 patients, respectively (χ 2=12.23, P=0.002). The vaccination coverage rates of Bacillus Calmette-Guerin (BCG) vaccine, the 3 rd dose of hepatitis B, the 3 rd dose of polio, the 3 rd dose of diphtheria-pertussis-tetanus, the 1 st dose of meningococcal polysaccharide group A, the 1 st dose of measles or measles and rubella vaccine, the 1 st dose of Japanese encephalitis vaccine, hepatitis A, measles-mumps-rubella, and group A+C meningococcal polysaccharide vaccine were 100.0% (192 cases), 94.3% (181 cases), 81.8% (157 cases), 88.5% (170 cases), 83.9% (161 cases), 76.6% (147 cases), 80.2% (154 cases), 68.2% (131 cases), 69.8% (134 cases), 54.7% (105 cases), respectively. Among the 73 patients who did not have their planned immunization completed, 57 cases (78.1%) gave up the vaccination due to parents′ concern of potential aggravation of their disease, and 16 cases (21.9%) had the plan discontinued by the immunization department because of the disease. Fever, local redness and swelling were the most common side-effects after vaccination both in SMA patients and healthy children (19.8% (38/192) vs. 18.8% (36/191) , χ 2=0.055, P=0.815). The main abnormal reactions of vaccination were rash and neurovascular edema, without significant difference between these two groups (2.6% (5/192) vs. 3.7% (7/191), χ 2=0.355, P=0.551). The coverage rate of Influenza and pneumococcal vaccine in SMA patients were 22.4% (43 cases) and 31.8% (61 cases), respectively. The incidence of pneumonia in the SMA patients decreased from 59.0% (23/39) to 41.0% (16/39) after vaccination. And none of the Influenza vaccinated patients had the flu in the year of vaccination. Conclusions:The coverage rate of National Immunization Program vaccines in the SMA children is low, especially in type 1 SMA patients, which is mainly due to their guardians′ concern of potential adverse events, even though the incidence of adverse reactions is similar in SMA patients and healthy children. Influenza and pneumococcal vaccine can reduce the risk of pneumonia and flu in children with SMA effectively.

Objective:To investigate the technical points and clinical application of combined infratemporal fossa approaches (CIFA) by analyzing the clinical results with CIFA for lesions involved skull base.Methods:A retrospective study was performed on 11 patients underwent CIFA for skull base lesions dissection from December 2014 to January 2019 in the department of otolaryngology, Peking Union Medical College Hospital. There were 6 male and 5 female patients, with age range of 16-72 years old and median age of 53 years old. Five patients underwent CIFA Type B and D, and the other 6 underwent CIFA A and B. All patients were followed up regularly by CT and MRI to observe possible recurrence.Results:Among the 5 patients with CIFA Type B and D, 3 were giant cell tumor and 2 were giant cell reparative granuloma, and median maximum cross-section size was 42 mm×46 mm (range from 37 mm×18 mm to 56 mm×53 mm). Among the 6 patients with CIFA Type A and B, 4 were paraganglioma of head and neck, 1 was schwannoma of skull base, 1 was petrous cholesteatoma, and median maximum cross-section size was 43 mm×36 mm (range from 24 mm×22 mm to 63 mm×35 mm). Nine patients underwent complete resection of the tumor in the first stage. In 2 patients, the extracranial parts were removed in the first stage, and the intracranial part was removed in the second stage. Tympanum and ossicular reconstruction were done in one of the CIFA Type B and group D, and 1 year′s postoperative hearing was mild conductive hearing loss. There was no cerebrospinal fluid leakage of all patients. All the 5 patients with normal facial nerve function before surgery recovered to H-B grade Ⅰ to Ⅱ within 3 months after surgery. Among the 4 patients whose preoperative facial nerve function were grade Ⅱ, 2 recovered to grade I after surgery and the other 2 were still grade Ⅱ. For the patient whose preoperative facial nerve function was grade Ⅴ, his postoperative recovery was grade Ⅲ. There was 1 patient whose pre-operative FN function was H-B grade Ⅲ, and the post-operative FN function was grade Ⅵ due to FN resection. Except for 2 cases with cochlear involved before surgery, cochleae of the other 9 cases were preserved. The follow-up time was 14 to 58 months. No recurrence was observed in all patients.Conclusions:The CIFA can safely and completely remove the extensive lesions that invade the skull base, and the facial nerve function can be well protected and recovered intro-and post-operation. Appropriate use of combined IFA can not only achieve good exposure and complete resection of lesions, but also create conditions for functional reconstruction.

OBJECTIVE：To struc turally modify shikimic acid ，and to investigate the reversal effects of its derivatives on paclitaxel-resistant human breast cancer cells MCF- 7/PTX. METHODS ：Using shikimic acid as the lead structure ，1-position carboxyl group was structurally modified to synthesize a series of shikimic acid derivatives through esterification ，amidation， hydrogenation and reduction ，etc. Using non-drug resistant cells MCF- 7 as reference ，MTT assay was used to screen derivatives with inhibitory activity as well as half-inhibitory concentration （IC50）and reversal index （RI）of derivatives to MCF- 7/PTX. With the drug resistance-related transgelin 2 as the target ，the molecular docking of the active derivatives with the drug resistance-related protein was carried out by using Glide 1.0 computer-aided design software. RESULTS ：Totally 15 derivatives were obtained （T1-T15）， of which T 4-T15 were obtained for the first time. MTT assay showed that （3R， 4S， 5R） -N-benzyl-3， 4， 5-trihydroxy-1-cyclohexene-1-formamide（T7），（3R，4S，5R）-N-（3，4，5-trihydroxy-1-cyclohexenylmethyl）-benzylamine（T14）， （3R，4S，5R）-3，4-O-isopropyl-5-O-acetyl-1-cyclohexene-1-methyl formate （T15）inhibited MCF- 7 and MCF- 7/PTX cells to a certain extent ；IC50 values of T 7，T14 and T 15 combined with pacliaxel to MCF- 7/PTX cells were significantly lower than that in negative control （Paclitaxel alone ）group（P＜0.05）. RIs of T 14 and T 15 were higher ，and RIs of the highest dose were 8.8 and 9.3， which were equivalent to positive control verapamil （10.8）. Th e results of molecular docking showed that the hydroxyl groups at positions 3，4 of T 7 could form multiple hydrogen bonds with ； Arg625 and Asp 627 in the catalytic region of transgelin 2. In addition to the hydrogen bond mentioned above at T 7，the mail：batistuta28@126.com secondary amine side chain at position 1 of T 14 could also form hydrogen bond with Glu 657 of transgelin 2. When the hydroxyl group on the T 15 mother nucleus was derived from the donor group ，the binding of the hydroxyl group to transgelin 2 was closer and the inhibition was enhanced. CONCLUSIONS ： The derivatives T 7，T14 and T 15 have certain reverse activity to paclitaxel-resistant human breast cancer cells. The polyhydroxy structure of the mother nucleus is the main structural region of the hydrogen bond between shikimic acid and its derivatives and transgelin 2. The derivation of its power supply group or the introduction of secondary amines and hydrophobic groups into the 1-carboxyl group of shikimic acid is benifit for enhancing the drug resistance reversal effect of derivative .

Objective To investigate the effect of oxcarbazepine(OXC) and sodium valproate(VPA) on electroencephalogram(EEG) and peripheral blood levels of homocysteine(Hcy) and asymmetric dimethylarginine(ADMA) in adult patients with partial epilepsy.Methods From May.2014 to May.2015,a total of 100 patients with partial epilepsy were enrolled and randomly divided into treatment group(treated with OXC) and control group(treated with VPA),with 50 cases in each group.After treatment,changes of EEG indices,Hcy,ADMA,cognitive function and adverse reaction were analyzed.Results Before treatment,there was no significant difference of EEG indices between the two groups(P>0.05).After treatment,the incidence rates of α wave decreasing more than 0.5 Hz,increasing of θ wave and increasing of δ wave were significantly different(P< 0.05).Before treatment,there was no significant difference of serum Hcy and ADMA levels between the two groups(P>0.05).After treatment,serum Hcy and ADMA levels were both significantly increased(P<0.05).Before treatment,Mini-mental State Examination(MMSE) scores of the two groups were without significant difference(P>0.05).After treatment,MMSE score of treatment group was higher than that of control group(P<0.05).In treatment group,there were 1 case of skin rash and 2 cases of gastrointestinal discomfort,which were self-improved.In control group,there were 3 cases of dizziness,5 cases of skin rash and 1 case of gastrointestinal discomfort,which were self-improved.Conclusion The effects of OXC and VAP on peripheral blood levels of Hcy and ADMA could be similar,and compared with VAP,OXC could significantly improve cognitive function in patients with epilepsy.

Objective To explore the correlation of the indoor carbon monoxide concentration and chronic diseases by monitoring the indoor carbon monoxide concentration timely.Methods Collected the data of non-traumatic patients(n=80)from July 201 1 to January 2014,and assigned them into the experiment group with carbon monoxide concentration measured and the control group without measured.All the subjects were further divided into one group with complaint of carbon monoxide poisoning and the other one without.For patients exposed to high concentration of carbon monoxide,carboxyhemoglobin was also measured and APACHEⅡ was scaled,and the relationship between them was analyzed.The confirmation and misdiagnosis rate of carbon monoxide poison-ing were calculated.For the patients with acute exacerbation of chronic diseases like chronic cardiac failure,chronic obstructive pul-monary disease,cerebral infarction induced by carbon monoxide poisoning,BNP,CAT and NIHSS were documented on admission and during follow-up with removal of carbon monoxide exposure and compared respectively.Results The relationship between blood carboxyhemoglobin,APACHEⅡ scores on admission and indoor carbon monoxide concentration was linear,and obviously positive.Between the experiment group(n=40)and the control group(n=40),there was significant difference(P <0.05)in confirma-tion rate and misdiagnosis rate with 80.00% vs.55.00% and 6.25% vs.81.80% respectively.For the 54 patients with carbon monoxide poisoning diagnosed,the changes between before and after removal of carbon monoxide exposure of the CAT scores of chronic obstructive pulmonary disease and NIHSS score of CI disease and myoglobin,troponin I,creatine kinase isoenzyme,BNP for chronic cardiac failure were significantly different(P <0.01).Conclusion The indoor carbon monoxide concentration may indicate the severity of carbon monoxide poi-soning,which could increase the confirmation rate of carbon monoxide poisoning,and reduce the misdiagnosis rate.It is helpful to identify carbon monoxide exposure,the common inducing factor,so as to improve the patients′clinical symptoms.