ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus（AFI） and Aurantii Fructus（AF） based on the total statistical moment analysis and molecular connectivity index（MCI）. MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） were consulted to establish the chemical composition database of AFI and AF， and set up their fingerprints by ultra-high performance liquid chromatography（UPLC）， and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI， all components of AFI and AF were divided into different component groups， the average values of 0-8^th order（⁰χ-⁸χ） MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment（AUC_T） of AFI and AF were （10.57±2.45）×10⁶， （5.09±0.89）×10⁶ μV·s， the values of total first-order moment（MCRT_T） were （11.57±1.58）， （12.10±1.29） min， the values of total second-order moments（VCRT_T） were（24.49±2.30）， （26.49±2.54） min²， respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin， hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI， such as alysifolinone and imperatorin， and the non-common components of AF， such as neoeriocitrin and isosakuranin， with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories， and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997， the average values of ⁰χ-⁸χ MCI of alkaloids in AFI and AF were 3.65 and 3.14， the average values of ⁰χ-⁸χ MCI of flavonoids were 8.47 and 8.47， the average values of ⁰χ-⁸χ MCI of volatile oils were 2.71 and 3.48， respectively. It showed that there were some differences in MCI of chemical constituents（groups） between AFI and AF. ConclusionThe chemical constituents（groups） of AFI and AF not only differ in content and species， but also in structural characteristics and structure-activity relationship， which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.

ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1（SLC8A1） mRNA in the myocardium of healthy organ donors （n=24） and heart failure （HF） patients （n=21） were assessed by real-time quantitative polymerase chain reaction （RT-qPCR） assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts （mCFs） with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay， respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation （RIP） was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 （Idh2） mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients， while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression， and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA （siRNA） could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.

Objective: To investigate the incidence density of adult sleep disorders (SD) in Yinzhou District, Ningbo City, Zhejiang Province from 2017 to 2023, so as to provide insights into formulating the control measures of SD. Methods: The electronic health records of permanent residents aged 18 years and over in Yinzhou District from 2017 to 2023 were collected through the Yinzhou Regional Health Information Platform. New cases of SD were diagnosed for the first time a year after establishing health records. The incidence density was estimated using Poisson distribution. The temporal, population and regional distribution characteristics of new cases of SD were analyzed using a descriptively epidemiological method. Results: From 2017 to 2023, there were 1 255 129 permanent residents aged 18 years and over in Yinzhou District, with a total observed person-time of 6 292 884 person-years and a median of 5.67 (interquartile range, 3.74) person-years. There were 165 490 new cases of SD, including 67 095 males (40.54%) and 98 385 females (59.46%). The incidence density of SD in Yinzhou District from 2017 to 2023 was 26.30/1 000 person-years, with no significant trend observed (P>0.05). The incidence density of SD was higher in females than in males (29.63/1 000 person-years vs. 22.57/1 000 person-years, P<0.05). The highest incidence density of SD was observed in individuals aged 70 to <80 years (63.30/1 000 person-years), and the lowest was in individuals aged 18 to <30 years (7.24/1 000 person-years). The incidence density of SD in individuals aged 30 years and over was higher than that in individuals aged 18 to <30 years (all P<0.05). The incidence density of SD was 32.03/1 000 person-years in individuals with junior high school education or below, which was higher than individuals with senior high school/technical secondary school education (25.93/1 000 person-years) and college degree and above (18.87/1 000 person-years, all P<0.05). Dongliu Street, Dongjiao Street, and Baihe Street had relatively higher incidence densities of SD, at 45.11/1 000 person-years, 42.87/1 000 person-years and 40.16/1 000 person-years, respectively. Conclusions From 2017 to 2023, there was no significant trend in the incidence density of SD in Yinzhou District. Higher incidence density were observed in females, the elderly, and individuals living in central urban areas.

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

Objective:To explore the risk factors for death within 1 year after hip fracture surgery in the elderly.Methods:A case control study was made on the clinical data of 551 elderly patients with hip fracture treated in Second Affiliated Hospital of Soochow University from January 2019 to December 2020, including 182 males and 369 females; aged 65-100 years [80(73,86)years]. Joint replacement, cannulated screw fixation or proximal femoral nail fixation were performed. The patients were divided into survival group ( n=494) and death group ( n=57) based on the death within 1 year after surgery recorded at postoperative telephone follow-up. The gender, age, hypertension, diabetes, cardiovascular diseases, chronic respiratory diseases, neurological diseases, chronic renal failure, anemia on admission, fracture types, American anesthesiologist Association (ASA) classification, operative methods, preoperative waiting time, duration of operation and perioperative blood transfusion were recorded in two groups. Univariate Cox regression was used to analyze the correlation between the above indexes and death within 1 year after surgery. All indexes with P<0.2 in the univariate analysis were included in multivariate Cox regression analysis to clarify the independent risk factors for death within 1 year after surgery. Results:Univariate Cox regression analysis showed that death within 1 year after surgery correlated with gender, age chronic respiratory diseases, chronic renal failure and anemia on admission (all P<0.01), but not with hypertension, diabetes, cardiovascular diseases, neurological diseases, fracture types, ASA classification, operative methods, preoperative waiting time, duration of operation or perioperative blood transfusion (all P>0.05). Multivariate Cox regression analysis showed that male ( HR=2.08, 95% CI 1.20, 3.61, P<0.01), age ≥ 80 years ( HR=2.22, 95% CI 1.15, 4.28, P<0.05), chronic respiratory diseases ( HR=2.54, 95% CI 1.19, 5.40, P<0.05), chronic renal failure ( HR=4.57, 95% CI 1.27, 16.44, P<0.05), anemia on admission ( HR=2.82, 95% CI 1.38, 5.76, P<0.01) were significantly associated with death within 1 year after surgery. Conclusion:Male age≥ 80 years, chronic respiratory disease, chronic renal failure and anemia on admission are independent risk factors for death within 1 year after hip fracture surgery in the elderly.

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1^LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8⁺ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Objective:To explore the surgical method and therapeutic effect of repairing thumb pulp defect with pedicled transposition of radial proper palmar digital artery flap of middle finger.Methods:Since June, 2006 to May, 2020, 17 cases(17 fingers) with thumb pulp defect were repaired by pedicled transposition of radial proper palmar digital artery flap of middle finger. The sizes of flap ranged from 1.5 cm × 1.5 cm to 4.2 cm × 2.0 cm. The antegrade pedicled flap of radial proper palmar digital artery of middle finger was used in 2 cases and the retrograde pedicled flap of middle finger was used in 15 cases. After the flap was resected, the donor sites were covered with a medium thickness skin graft transferred from the wrist or elbow. The skin graft did not need to be packed. The dorsal branch of the digital nerve was included in the flap and it was anastomosed with the proper nerve of the injured thumb stump. After 16-22 days of the operation, the pedicles were cut off. The patients were instructed to perform digit function exercise after the pedicle was cut off. After the operation, the patients were included in regularly follow-up through outpatient visit, telephone or WeChat interview. The appearance and sensation of the thumb and finger pulps and the function recovery of the thumb and finger joints were observed through the followed-ups.Results:All 17 flaps and donor site skin grafts survived over 3 to 32 months of follow-up. The flaps achieved good texture and natural appearance. The TPD recovered to 5~11 mm. According to the Michigan Hand Function Questionnaire, all the 17 patients were very satisfied with the overall appearance and function of the hands. According to TAM, the 17 cases were all in excellent.Conclusion:Repairing thumb pulp defect with radial proper palmar digital artery pedicled flap of middle finger, the flap resection is simple, and the donor site is hidden. The appearance and texture of flap is good. It is a safe, effective and good method.

Objective: To evaluate the effectiveness of professional competency training on the psychological commissioners in college,and to provide a reference for promoting mental health education in colleges. Methods: Using the purposive sampling method, 198 psychological commissioners and 210 nonpsychological commissioners from freshmen in a university in Nanjing were selected for questionnaire survey. SPSS 21.0 statistic software was utilized for data analysis. Results: The levels of knowledge and skills of mental health practice among trained psychological commissioners showed no difference with those nonpsychological commissioner students before training(t=0.34, -0.08, P>0.05). Compared with pretraining, the paired sample ttest indicated that knowledge, practical skills, and expected skills among qualified psychological commissioners increased significantly after training, respectively(t=23.34, 23.21, 3.30, P<0.01). Understanding of job duty, basic helping skills, interpersonal communication, mental problems among college students, classroombased psychological activities, psychological counseling, mental disorders identification, group counseling and crisis intervention increased significantly after training(P<0.01). Conclusion The professional competency training could substantially improve mental health practice, skills, as well as attitudes among psychological commissioners recruited from college freshmen.

Objective: To explore two-dimensional speckle tracking imaging (2D-STI) in evaluation on the changes of left atrial function in patients with paroxysmal atrial fibrillation before and after radiofrequency catheter ablation (RFCA). Methods: Echocardiography was performed on 30 patients with paroxysmal atrial fibrillation (AF group) treated by radiofrequency catheter ablation in the preoperation and postoperative 3 days, 1 month, 3 months. Thirty healthy volunteers were selected as the control group. The left atrial anteroposterior diameter (LAD), early diastolic transmitral flow velocity (E peak), mitral annular early diastolic motion velocity (Em), left atrial maximum, minimum and pre-systolic volume (LAVmax, LAVmin and LAVP) were measured and E/Em, left atrial active ejection fraction (LAAEF), left atrial passive ejection fraction (LAPEF) were calculated by conventional echocardiography. Left atrial strain and strain rate curves of each segment were obtained by 2D-STI, and the mean peak strain (mSs, mSe, mSa) and strain rate (mSRs, mSRe, mSRa) of the left atrial in the left ventricular systolic, the early diastolic stage and the late diastolic stage, and left atrial stiffness (LASt) was measured and calculated. The changes of the left atrial structure and function in patients with paroxysmal atrial fibrillation before and after RFCA were compared. Results: Compared with the control group, LAD, LAVp, LAVmin, LAVmax, E/Em and LASt increased in the AF group, LAPEF, LAAEF, E peak, Em, mSs, mSe, mSa, mSRs, mSRe and mSRa decreased (all P<0.05). There were statistically significant differences in left atrial strain parameters and LASt of patients with paroxysmal atrial fibrillation before and 3 days, 1 month and 3 months after RFCA (all P<0.05). Compared with the preoperative, mSs, mSe, mSa, mSRs, mSRe and mSRa decreased and LASt was increased at 3 days after RFCA (all P<0.05); mSs, mSe, mSa, mSRs, mSRe and mSRa increased, and LASt decreased at 3 months after RFCA (all P<0.05). Compared with the postoperative 3 days, mSs, mSe, mSa, mSRs, mSRe and mSRa increased, LASt decreased (all P<0.05) at 1 month and 3 months after RFCA. Compared with the postoperative 1 month, mSRs increased at 3 months after RFCA (P<0.05). Conclusion: The left atrium function of patients with paroxysmal atrial fibrillation decrease at 3 days after RFCA, the pump function improved 1 month after RFCA, and the left atrial reservoir, conduit and pump function improve observably at 3 months after RFCA.

Objective To analyze the clinical data of brucellosis,and to provide references for brucellosis therapy.Methods The patients definitely diagnosed brucellosis at the First Affiliated Hospital of Zhengzhou University from January 2013 to June 2016 were assessed,data of clinical features,laboratory examination,treatment and prognosis were analyzed.Results Of all 99 cases,the mean age was (46.7 ± 15.7) years old,83 cases had a history of closely contacted with sheep,2 cases with pig and 1 case with cattle.The occupational distribution of patients included 90 farmers,1 veterinarian,2 cooks,6 children and students.All patients had clinical manifestations such as fever,fatigue,and sweating.There were 18 patients with back and joint pain,13 cases had abnormal manifestation on magnetic resonance imaging (MRI).Blood culture was positive in 54 (71.05％,54/76) and serum test tube agglutination test was positive in 61 (98.39％,61/62).Eighty-one patients received doxycycline combined with rifampicin treatment,six months laters,all patients were cured.Conclusions Sheep are the main sources of infection for brucellosis.Fatigue,sweaty and fever are the most common symptoms,and osteoarticular is the most frequently involved.Serum agglutination test and blood culture are important tests for diagnosis of brucellosis.Doxycycline combined with rifampicin was the most common used antibiotics regimen.Early,combined,regular,full-course antibiotic treatment has a better prognosis.