Objective To investigate the regulatory mechanism of Notch signaling pathway by YAP in non-alcoholic steatohep-atitis(NASH)liver fibrosis,and assess the intervention effect of Cigu Xiaozhi prescription in detoxification and phlegm treatment.Methods C57BL/6J mice were randomly divided into different groups,including a normal group,NASH liver fibrosis model group,verteporfin(VP)intervention group,VP+Chinese medicine(Cigu Xiaozhi prescription)low-dose group,VP+Chinese medicine high-dose group,and dimethyl sulfoxide control group.The methionine/choline-deficient diet combined with low-dose CCl4 was used to construct the NASH liver fibrosis model.The degree of liver fibrosis was evaluated using hematoxylin and eosin(HE)and Masson staining.Four protein factors associated with liver fibrosis were detected using enzyme-linked immunosorbent assay,and hydroxyproline levels in the mouse liver was determined using the alkaline water method.The localization of α-SMA,ColⅠ,YAP,and Notch1 proteins in the liver was determined using immunohistochemistry.Additionally,the mRNA and protein expression levels of the Notch signaling pathway molecules,namely Notch1/2,J agged1,and DLL4,were assessed using real-time quantitative PCR and Western blotting analyses,respectively.Results The HE and Masson staining results revealed that the liver cells of NASH liver fibrosis mice were swollen and the cytoplasm was transparent.Additionally,evident fibrosis was observed in the hepatic lobule,portal area,and sinus;it was accompanied by heightened levels of inflam-matory cell infiltration,a large number of fat droplets,and instances of local hepatocyte necrosis,dissolution,and cirrhosis.The four factors associated with liver fibrosis showed a substantial increase(P<0.01).α-SMA,ColⅠ,YAP,and Notch1 were localized in the cytoplasm of hepatocytes.YAP,Notch1/2,and Jagged1 were highly expressed in the liver(P<0.01)but were downregulated after intervention with VP and VP+high and low doses of Cigu Xiaozhi prescription(P<0.05).Meanwhile,DLL4 factor was upregulated in the VP+high-dose of Cigu Xiaozhi prescription group(P<0.05).Conclusion YAP may inhibit activation of the Notch pathway by downregulating Notch1/2 and Jagged1 and upregulating DLL4,thereby interfering with the occurrence of liver fibrosis in NASH.Treatment with Cigu Xiaozhi pre-scription may inhibit Notch signaling pathway activation by downregulating YAP,Notch1/2,and Jagged1 and upregulating DLL4 through its multi-components and multi-targets properties,ultimately slow the progression of liver fibrosis in NASH.

ObjectiveTo explore the evolution principles of symptoms including deficiency， phlegm and blood stasis， and of the functional near-infrared spectroscopy （fNIRS） cerebral hemodynamic characteristics at various stages in patients of Alzheimer's disease. MethodsA total of 497 patients with complaint of memory loss were included， and were divided into subjective cognitive decline （SCD） group （198 participants）， mild cognitive impairment （MCI） group （228 participants） and dementia （AD） group （71 participants）. Neuropsychological evaluation， traditional Chinese medicine （TCM） syndrome investigation， and fNIRS data collection of prefrontal cortex were performed in each group. Descriptive statistics were used to analyze the distribution of TCM syndromes and the difference of TCM syndrome scores in each group； logistic regression was used to analyze the influence of TCM syndromes on the incidence of the patients； association rules were used to analyze the TCM syndromes of the patients； the hemodynamic characteristics of fNIRS in the prefrontal cortex of each group were compared. ResultsKidney essence deficiency syndrome was the dominant syndrome in all stages of AD. There were statistically significant differences in the distribution frequency of kidney essence deficiency， phlegm turbidity obstructing orifices， blood stasis obstructing collaterals， qi and blood deficiency， heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes among the three groups （P＜0.01）， and the scores of kidney essence deficiency syndrome among the three groups were statistically significant （P＜0.01）. Logistic regression analysis showed that kidney essence deficiency， and qi and blood deficiency syndromes were the main risk factors for the SCD group （P＜0.05）， phlegm turbidity obstructing orifices syndrome was the main risk factor for the MCI group （P＜0.05）， and heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes were the main risk factors for the AD group （P＜0.05）. The association rule analysis showed that the combination of kidney essence deficiency plus phlegm turbidity obstructing orifices had the highest support （33.33%） in the SCD group， and the combination of kidney essence deficiency plus blood stasis obstructing collaterals had the highest support （32.90% and 52.13%） in both the MCI and AD group. The prefrontal fNIRS results showed that the mean ∆HbO₂ concentration in the left dorsolateral prefrontal cortex （LDLPFC） decreased sequentially among the three groups （P＜0.05）， and the mean ∆HbO₂ concentration in the LDLPFC was negatively correlated with the MoCA score among the three groups （r = -0.142， P＜0.05）. Further analysis showed that the mean ∆HbO₂ concentration in the LDLPFC of patients with kidney essence deficiency syndrome were statistically significant differences among the three groups （P＜0.05）. ConclusionKidney deficiency is the basis of the pathogenesis of AD， and the key brain area damaged is the LDLPFC. Turbid pathogens such as phlegm and blood stasis are the pathological factors that aggravate the disease， and the syndromes of AD show the evolution law of deficiency and excess as “kidney deficiency→phlegm turbidity→blood stasis→turbid toxin”. The changes in prefrontal hemodynamics based on fNIRS are consistent with the changes in the characteristics of symptoms， which can be used to assess the degree of cognitive impairment in AD patients.

Objective This study aimed to identify differentially methylated genes (DMGs) associated with natural killer cells in patients with autoimmune thyroiditis (AIT),focusing on the influence of varying water iodine exposure levels. Methods Participants were divided into categories based on median water iodine (MWI) concentrations:iodine-fortified areas (IFA,MWI<10 μg/L),iodine-adequate areas (IAA,40 ≤ MWI ≤ 100μg/L),and iodine-excessive areas (IEA,MWI>300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89,40,and 47 pairs for IFA,IAA,and IEA,respectively. DMGs were identified using 850K BeadChip analysis for 10/10 paired samples. Validation of DNA methylation and mRNA expression levels of the DMGs was conducted using MethylTarget? and QRT-PCR for 176/176 paired samples. Results KLRC1,KLRC3,and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed,whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore,KLRC1 was hypomethylated and highly expressed in both IFA and IEA. Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally,DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.

OBJECTIVE To investigate the protective effect of cryptotanshinone on premature ovarian insufficiency （POI） rats and its potential mechanism based on stromal cell-derived factor-1 （SDF-1）/CXC subfamily receptor 4 （CXCR4） axis. METHODS POI rat model was established by intraperitoneal injection of vinylcyclohexene （VCD）. The successfully modeled rats were randomly divided into model group， cryptotanshinone low-dose group （50 mg/kg）， cryptotanshinone high-dose group （100 mg/kg）， and cryptotanshinone high-dose+AMD3100 group （100 mg/kg cryptotanshinone+2.5 mg/kg CXCR4 inhibitor AMD3100）， with 10 rats in each group. Another 10 rats were injected with normal saline instead of VCD as the control group. Rats in each drug group were given intragastrical or （and） intraperitoneal injection of the corresponding drug once a day for 4 weeks. The levels of estradiol （E2）， luteinizing hormone （LH） and follicle-stimulating hormone （FSH） in serum and reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in ovarian tissue were detected in each group. The morphology of ovarian tissue was observed. The cell apoptosis of ovarian tissue， as well as the mRNA expressions of SDF-1， CXCR4 and the protein expressions of caspase-3， B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， SDF- 1， CXCR4 were detected. RESULTS Compared with the control group， the ovarian atrophied， the number of primitive follicles decreased， the number of atretic follicles increased， and the damage was obvious in the model group. Serum E2 level， SOD and GSH-Px levels in ovarian tissue， the mRNA expressions of SDF-1 and CXCR4， and the protein expressions of Bcl-2， SDF-1 and CXCR4 in ovarian tissue were all significantly decreased or down-regulated； the levels of FSH and LH in serum， ROS and MDA levels in ovarian tissue， the cell apoptosis rate， and the protein expressions of caspase-3 and Bax in ovarian tissue mail：k26awn@163.com were increased or upregulated significantly （P＜0.05）. Compared with model group， the ovarian tissue lesions of rats in cryptotanshinone low-dose and high-dose groups were significantly improved， and each quantitative index was significantly improved （P＜0.05）. AMD3100 could significantly reverse the improvement effect of cryptotanshinone on the above indexes （P＜0.05）. CONCLUSIONS Cryptotanshinone can reduce ovarian cell apoptosis and oxidative stress in POI rats by activating the SDF-1/CXCR4 axis， regulating serum hormone levels， thereby improving ovarian injury.

Objective:To revise and evaluate the reliability and validity of the Healthcare Provider Perceptions of Team Effectiveness (Provider-PTE) .Methods:The English version of the Provider-PTE was translated literally and back in accordance with the Brislin translation principles. Questionnaire culture debugging and item revision were conducted through Delphi method and pre-survey. In March 2022, a survey was conducted among 641 nurses from two ClassⅢ Grade A hospitals in Qingdao to test the reliability and validity of the questionnaire. A total of 641 questionnaires were distributed, and 605 valid questionnaires were recovered, with an effective recovery rate of 94.4%.Results:The Chinese version of Provider-PTE included five dimensions, including role development, team support, team meetings, team operations, and care outcomes, with a total of 26 items. Through exploratory factor analysis, the cumulative variance contribution rate of the five common factors was 84.783%. The average scale content validity index of the Provider-PTE was 0.928, and the item content validity index was 0.875 to 1.000. The Cronbach's α coefficient of the Chinese version of Provider-PTE was 0.859, and the retest reliability was 0.873.Conclusions:The Chinese version of Provider-PTE has good reliability and validity, and can be used to assess the team effectiveness of nursing staffs.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To investigate the application effect of medical sterile gloves-assisted cutting cloth samples in the repair of finger degloving injury.Methods:The clinical data of patients with finger skin and soft tissue degloving defects treated in Jiangnan Hospital Affiliated with Binjiang College of Zhejiang University of Traditional Chinese Medicine from April 2015 to December 2021 were analyzed retrospectively. Medical sterile gloves were used to make cloth samples of finger defects, and then the dorsal foot flap or toenail flap was cut according to the cloth samples to repair finger defects. The survival of flaps and the appearance of the fingers’ body were observed after surgery, and the patients’ satisfaction was investigated. The finger function was evaluated by the trial standard of upper limb function evaluation of the Hand Surgery Society of Chinese Medical Association.Results:A total of 12 patients with 13 fingers were enrolled. There were 9 males (10 fingers) and 3 females (3 fingers), aged 17-54, average of 37-year-old. There were 5 cases (5 fingers) in the left hand and 7 cases (8 fingers) in the right hand, all with unilateral finger injury. The size of the dorsal flaps and great toenail flaps harvested were appropriate, ranging from 5.5 cm×4.5 cm to 10.5 cm×5.8 cm. After surgery, all patients were regularly followed up for 3-15 months, an average of 7 months. All the dorsal flap and great toenail flap of the foot after surgery survived, and the appearance of the finger body was not bloated. All patients were very satisfied with the appearance and function of the hand, and the finger function was evaluated as excellent in 7 cases and good in 5 cases.Conclusion:The application of sterile gloves-assisted cutting cloth samples for the treatment of finger degloving injury can simplify the procedure, reduce donor damage, make up for the lack as much as needed, and the repaired fingers can obtain better shape and function.

Objective:To investigate the application effect of medical sterile gloves-assisted cutting cloth samples in the repair of finger degloving injury.Methods:The clinical data of patients with finger skin and soft tissue degloving defects treated in Jiangnan Hospital Affiliated with Binjiang College of Zhejiang University of Traditional Chinese Medicine from April 2015 to December 2021 were analyzed retrospectively. Medical sterile gloves were used to make cloth samples of finger defects, and then the dorsal foot flap or toenail flap was cut according to the cloth samples to repair finger defects. The survival of flaps and the appearance of the fingers’ body were observed after surgery, and the patients’ satisfaction was investigated. The finger function was evaluated by the trial standard of upper limb function evaluation of the Hand Surgery Society of Chinese Medical Association.Results:A total of 12 patients with 13 fingers were enrolled. There were 9 males (10 fingers) and 3 females (3 fingers), aged 17-54, average of 37-year-old. There were 5 cases (5 fingers) in the left hand and 7 cases (8 fingers) in the right hand, all with unilateral finger injury. The size of the dorsal flaps and great toenail flaps harvested were appropriate, ranging from 5.5 cm×4.5 cm to 10.5 cm×5.8 cm. After surgery, all patients were regularly followed up for 3-15 months, an average of 7 months. All the dorsal flap and great toenail flap of the foot after surgery survived, and the appearance of the finger body was not bloated. All patients were very satisfied with the appearance and function of the hand, and the finger function was evaluated as excellent in 7 cases and good in 5 cases.Conclusion:The application of sterile gloves-assisted cutting cloth samples for the treatment of finger degloving injury can simplify the procedure, reduce donor damage, make up for the lack as much as needed, and the repaired fingers can obtain better shape and function.

OBJECTIVE To study the intervention effects and mechanism of Compound yu ’e nasal drops on ovalbumin induced allergic rhinitis in rats . METHODS The allergic rhinitis model of rat was induced with ovalbumin . Model rats were randomly divided into model group ，triamcinolone acetonide group （positive control ，0.026 mg/kg），Compound yu ’e nasal drops high-dose，medium-dose and low -dose groups （134.4、67.2、33.6 mg/kg），12 rats in each group . Another blank control group was set. Except for blank control group ，the corresponding drugs were given by nasal drip twice a day for 14 days. One hour after last administration，the nasal symptom scores of rats were recorded ；the levels of serum immunoglobulin E （IgE），interleukin-2（IL- 2），IL-13 and tumor necrosis factor -α（TNF-α）were measured by enzyme -linked immunosorbent assay . The changes of nasal mucosa in rat were observed by HE staining . The expressions of TNF -α，IL-2 and IL -13 in nasal mucosa were detected by Western blot. RESULTS Compared with blank control group ，nasal symptom score and the levels of serum IgE ，IL-2，IL-13，TNF-α in model group were increased significantly （P＜0.01）；obvious pathological injury was found in nasal mucosa ，and the expressions of TNF -α，IL-2 and IL -13 protein were increased significantly （P＜0.01）. Compared with model group ，Compound yu ’e nasal drops significantly reduced the nasal symptom score ，the levels of serum IgE ，IL-2，IL-13，TNF-α to different extents ，improved pathological injury of nasal mucosa and significantly inhibited the expressions of TNF -α，IL-2 and IL -13 protein（P＜0.05 or P＜ 0.01）. CONCLUSIONS Compound yu ’e nasal drops play significant effects against allergic rhinitis in rats by regulating the balance of t ype 1 helper T cells/type 2 helper T cells ，balancing and inhibiting the secretion of inflammatory cytokines .