ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 （Fas）/cysteine protease-8 （Caspase-8）/cysteine protease-3 （Caspase-3） signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury （CLI）. MethodsAmong 48 Wistar rats，12 rats were randomly selected as the blank group，and the other rats were administered alpha-naphthalene isothiocyanate （ANIT） by gavage to induce a CLI model. The modeling rats were randomly divided into the model group， the ursodeoxycholic acid group（0.1 g·kg^-1） and the Yinchenhao Tang group（9.23 g·kg^-1），with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），gamma-glutamyl transpeptidase （γ-GT），total bilirubin （TBil） and total bile acid （TBA） in serum were detected. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3，B-cell lymphoma-2 （Bcl-2） associated X protein （Bax） and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with those in the blank group，the levels of ALT，AST，ALP，γ-GT，TBA and TBil in serum of the model group were significantly increased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased （P<0.01）. The arrangement of hepatocytes was disordered，and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly increased（P<0.05，P<0.01），while the protein and mRNA expressions of Bcl-2 were significantly decreased （P<0.05，P<0.01）. Compared with those in the model group，the levels of ALP，γ-GT，TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased（P<0.05，P<0.01）. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the mRNA expression of Bcl-2 was significantly increased （P<0.05，）. The levels of ALT，AST，γ-GT，TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased （P<0.05，P<0.01）. The protein expression of Fas and Bax and the mRNA expression of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the protein and mRNA expression of Bcl-2 were significantly increased （P<0.05，P<0.01）. Hepatocyte injury，inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI，and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.

ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury （CLI） by inhibiting toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） pathway via regulating farnesol X receptor （FXR）. MethodsA total of 40 Wistar male rats were randomly selected， with 10 as a blank group，and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate （ANIT）. After modeling，they were randomly divided into the model group， the ursodeoxycholic acid （0.1 g·kg^-1） group and the Yinchenhao Tang （9.23 g·kg^-1） group，with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），γ-glutamyl transpeptidase （γ-GT），total bile acid （TBA），total bilirubin （TBil） and direct bilirubin （DBil） levels in serum were detected. Tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6） levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR，TLR4，MyD88，NF-κB，F4/80，TNF-α，IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR，TLR4，MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. ResultsCompared with those in the blank group，ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the model group were significantly increased （P<0.01）. The levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were significantly increased （P<0.01），and the mRNA and protein expressions of FXR in liver tissue were decreased （P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased （P<0.05，P<0.01）. Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group，ALT，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.05，P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased （P<0.05，P<0.01）. ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.01）. The mRNA and protein expressions of FXR in liver tissue were significantly increased，and the mRNA expressions of TLR4，MyD88，NF-κB，and F4/80， as well as the protein expressions of TLR4 and NF-κB were obviously decreased （P<0.05，P<0.01）. The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI，and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.

Resistance training promotes protein synthesis and hypertrophy, enhancing strength of skeletal muscle through the activation of the mammalian target of rapamycin (mTOR) and the subsequent increases of ribosome biogenesis and translation capacity. Recent studies indicate that resistance training has positive effects on physical fitness and illness treatment, yet the mechanisms underlying hypertrophic adaptation remain insufficiently understood. Human studies focused on the correlation between mTOR signals and hypertrophy-related protein production, while animal research demonstrated that mTOR complex 1 (mTORC1) is the main regulator of resistance training induced-hypertrophy. A number of upstream factors of mTORC1 have been identified, while the downstream mechanisms involved in the resistance training induced-hypertrophy are rarely studied. mTORC1 regulates the activation of satellite cells, which fuse with pre-existing fibers and contribute to hypertrophic response to resistance training. This article reviews the research progress on the mechanism of skeletal muscle hypertrophy caused by resistance training, analyzes the role of mTOR-related signals in the adaptation of skeletal muscle hypertrophy, and aims to provide a basis for basic research on muscle improvements through resistance training.
TOR Serine-Threonine Kinases/physiology* ; Resistance Training ; Humans ; Signal Transduction/physiology* ; Muscle, Skeletal/physiology* ; Hypertrophy ; Animals ; Mechanistic Target of Rapamycin Complex 1

OBJECTIVES: To study the therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective To explore the effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.

With the development of genetics and advances in genetic testing technology,the demand for cancer genetic counseling has increased dramatically.Advanced practice nurses play a key role in personalized health care delivery.The oncology genetic nurse-led genetic counseling services in foreign countries are becoming more and more mature,but in China,the work of oncology genetic counseling started late,and the combination of genetics/genomics with nursing is still in its infancy.There is still a lack of relevant research on oncology genetic nurses.This article introduced the qualification certification,core competence and clinical practice content of foreign oncology genetic nurses,and summarized the clinical practice effect of oncology genetic nurses and the enlightenment to China's advanced nursing practice,which provided references for the construction of oncology genetic nurses training programs and clinical service models suitable for China's national conditions,so as to meet the needs of the development of advanced nursing practice and the growing demand for precision oncology and high-quality genetic medical care.

ObjectiveTo explore the relationships between internet gaming disorder (IGD), interpersonal needs, loneliness, and depression in adolescents through the construction of a chain mediation model, to clarify the underlying mechanisms of these associations, and to provid a theoretical basis for depression prevention and intervention. MethodsBased on the data of the 7th Population Census, using convenient sampling method 1 106 adolescents aged between 10‒19 years in South China (176), North China (147), Central China (332), and East China (451) were selected to conduct a cross-sectional survey, with a ratio of 1∶1∶1.5∶2.5. The survey was conducted with a questionnaire consisting of general information (sex, age, grade, parents’ education level), the Chinese version of the IGDS9-SF, the INQ-15, the short-form of the ULS-8 and the PHQ-9 were used to evaluate the depression status of adolescents. Spearman correlation analysis was used to explore the correlation between the variables. A multiple-mediator model was constructed using IBM SPSS Statistics 22.0 PROCESS to examine the mediating effects of interpersonal needs and loneliness on the relationship between IGD and depression. The significance of the chain mediating effect was tested using the Bootstrap method. ResultsOverall, 39.06% (432/1 106) adolescents experienced depression. The incidence of depression among adolescents with smoking and without smoking was 62.50% and 38.36%, respectively. Similarly, the incidence of depression among adolescents with alcohol consuming and without alcohol consuming was 61.94% and 35.94%, respectively. There were statistically significant differences between IGD, interpersonal needs, loneliness, and depression (P<0.01). The chain mediation model demonstrated a good fit, and the bootstrap test showed that the 95%CI of each mediation path did not include 0, indicating significant mediation effects. The overall effect was 0.337. The direct effect of IGD on depression was significant (effect value=0.138, 95%CI:0.102-0.173, P<0.001). The mediation effects included three paths: ① IGD →interpersonal needs → depression (effect value=0.073, P<0.05), accounting for 21.47% of the total effect;② IGD→ loneliness → depression (effect value=0.093, P<0.05), accounting for 27.35%; and ③ IGD → interpersonal needs → loneliness → depression (effect value=0.036, P<0.05), accounting for 10.59%. ConclusionInterpersonal needs and loneliness independently and jointly mediate the relationship between IGD and depression among adolescents. To reduce depression and improve mental health in this population, measures should be taken to prevent and intervene in IGD, address adolescents’ social and emotional needs, enhance satisfaction of interpersonal needs, and reduce loneliness.

Objective:To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase(CML-CP).Methods:Clinical data of 41 adult CML-CP patients in Department of Hematology,Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed.The clinical characteristics and prognosis of patients between＜60 years group and ≥ 60 years group were compared.Results:The 41 patients included 27(65.9％)males and 14(34.1％)females.The median age of the patients was 56(19-84)years,with 22 cases(53.7％)＜60 years and 19 cases(46.3％)≥60 years.Univariate analysis indicated that the proportions of patients with comorbidities,intermediate/high-risk Sokal score,myelofibrosis,and lactate dehydrogenase ≥1 000 U/L were significantly increased in ≥60 years group compared with＜60 years group at initial diagnosis(all P＜0.05).There were no statistical differences in the distribution of sex,ELST score,white blood cell count,platelet count,peripheral blood basophil percentage,peripheral blood eosinophil percentage and bone marrow primitive cell percentage between the two groups(P＞0.05).The proportion of patients taking reduced-dose imatinib in≥60 years group significantly increased(P＜0.001).Patients＜60 years had a higher proportion of molecular biological remission after treatment of tyrosine kinase inhibitors(TKIs)than patients ≥ 60 years(P＜0.001).The incidence of non-hematologic adverse reactions to TKI therapy significantly increased in patients ≥ 60 years(P＜0.001).Multivariate analysis showed that no adverse factors affecting the efficacy and prognosis of TKI.Conclusion:Compared with adult CML-CP patients＜60 years,patients ≥ 60 years gain fewer benefits from TKI treatment and increased adverse reactions.

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