OBJECTIVE To optimize the extraction process of Shenye buyi formula. METHODS Based on the quality by design （QbD） concept， the contents of rutin， nuciferine， sinapine thiocyanate， liquiritin，and glycyrrhizic acid ammonium salt， as well as the extract yield， were selected as the critical quality attributes （CQAs） for the extraction process of Shenye buyi formula. The fishbone diagram combined with the failure model and effect analysis method was adopted to determine the water addition， extraction time and extraction times as critical process parameters （CPPs）. High-performance liquid chromatography was employed to detect the contents of rutin， nuciferine， sinapine thiocyanate， liquiritin， and glycyrrhizic acid ammonium salt. The analytic hierarchy process-entropy weight method was used to comprehensively assign weights to the content of the five components including rutin and the extract yield. The Box-Behnken response surface method was employed to fit the mathematical model between CQAs and CPPs， screen the operational space of the extraction process， and validate it. RESULTS The optimal operational space of the extraction process was 9.5 to 12 times the amount of water added， the extraction time was 1 to 1.7 hours， and the extraction times were 3. Upon verification，the comprehensive scores of the optimal extraction process within the operational space were 89.79 and 84.93， respectively. CONCLUSIONS The extraction process of the Shenye buyi formula can be applied to the development and production of its granule preparations.

Da Chaihutang， first recorded in Shanghanlun by Zhang Zhongjing of the Eastern Han dynasty， is composed of eight medicinal herbs， namely Bupleuri Radix， Scutellariae Radix， Rhei Radix et Rhizoma， Aurantii Fructus Immaturus， Paeoniae Radix Alba， Pinelliae Rhizoma， Zingiberis Rhizoma Recens， and Jujubae Fructus. It features a well-defined hierarchy of sovereign， minister， assistant， and courier ingredients. The prescription is characterized by its balanced compatibility， mutually restrained cold and warm properties， and combined use of harmonizing and purging therapeutic strategies. As a renowned classical formula indicated for harmonizing Shaoyang and purging internal heat accumulation， it is the core prescription for the treatment of Shaoyang-Yangming combined disease. A comprehensive review of modern research literature on Da Chaihutang reveals that its chemical composition is notably diverse. The core pharmacologically active material bases of its constituent single herbs have been clearly identified， including saikosaponins from Bupleuri Radix， flavonoids from Scutellariae Radix， anthraquinones from Rhei Radix et Rhizoma， flavonoids and alkaloids from Aurantii Fructus Immaturus， monoterpene glycosides from Paeoniae Radix Alba， alkaloids and organic acids from Pinelliae Rhizoma， gingerols from Zingiberis Rhizoma Recens， and polysaccharides and triterpenoid acids from Jujubae Fructus. In the compound formula， a total of 163 chemical constituents have been comprehensively identified， among which flavonoids and their glycosides constitute the most abundant component category. Flavonoids and their glycosides， monoterpene glycosides， and pentacyclic triterpenoid saponins are regarded as the core pharmacologically active substances of the whole formula. In addition， 9 potential quality markers that can comprehensively characterize the overall quality and core therapeutic efficacy of the whole formula have been screened out. Modern pharmacological studies have shown that the pharmacological effects of Da Chaihutang exhibit synergistic characteristics involving multiple components， multiple targets， and multiple pathways. Its core pharmacological activities encompass the regulation of digestive system disorders， including pancreatic protection， intervention in biliary tract diseases， and protection of gastrointestinal mucosa； intervention in hepatobiliary diseases such as non-alcoholic fatty liver disease and cholestatic liver injury； and regulation of metabolic disorders such as hypoglycemic effect， improvement of insulin resistance， and regulation of lipid metabolism. Furthermore， it also possesses multiple pharmacological activities， including intervention in atherosclerosis， regulation of immune and inflammatory responses， multi-organ protection， and anti-hepatocellular carcinoma effect. In modern clinical practice， Da Chaihutang and its modified formulas are mostly used in combination with conventional Western medical regimens. They have demonstrated notable therapeutic advantages in the treatment of digestive system diseases such as cholecystitis， acute pancreatitis， cholelithiasis， and non-alcoholic fatty liver disease， but also have shown definite curative efficacy in the management of diseases affecting multiple other systems， including cardiovascular， endocrine， dermatological， reproductive， respiratory， neurological， urinary， pediatric， and immune systems. These combined applications can effectively improve the overall clinical response rate， shorten the time to symptom relief， and reduce both the disease recurrence rate and the incidence of adverse reactions. This review systematically summarized the formula compatibility， chemical constituents， pharmacological mechanisms， and modern clinical applications of Da Chaihutang and its modified formulas， to provide a theoretical basis and practical reference for the secondary development of classic formulas， the research and development of new drugs， and the precise and safe clinical application of this classical prescription.

Objective:To evaluate the accuracy and feasibility of an automated scanning and uptake system to assist pathologists with hu-man epidermal growth factor receptor 2(HER2)FISH interpretation.Methods:HER2 gene amplification is detected using FISH,and"result interpretation by independent pathologists"is regarded as the"gold standard."The consistency of"human-machine dialogue results"(use of a CytoVision* system combined with manual interpretation)and"CytoVision*-based automated interpretation"with the"gold standard"was assessed.Results:Consistency between"human-machine dialogue results"and the"gold standard"can surpass 91%,with the former method saving up to 50%of the manual operation time.The tendency of each cell nucleus's HER2 copy number to be"underestimated"is the main reason for the low sensitivity observed in cases with low copy number amplification and HER2 heterogeneous expression cases in"human-machine dialogue interpretation."Conclusions:Automatic FISH image analysis and uptake systems simulate the process of manu-ally interpreted cell selection,ensure random cell selection,and improve work efficiency.With its accurate selection of the hybridization re-gion and"human-computer dialogue,"the system is expected to"replace"interpretation by independent pathologists.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective:To evaluate the accuracy and feasibility of an automated scanning and uptake system to assist pathologists with hu-man epidermal growth factor receptor 2(HER2)FISH interpretation.Methods:HER2 gene amplification is detected using FISH,and"result interpretation by independent pathologists"is regarded as the"gold standard."The consistency of"human-machine dialogue results"(use of a CytoVision* system combined with manual interpretation)and"CytoVision*-based automated interpretation"with the"gold standard"was assessed.Results:Consistency between"human-machine dialogue results"and the"gold standard"can surpass 91%,with the former method saving up to 50%of the manual operation time.The tendency of each cell nucleus's HER2 copy number to be"underestimated"is the main reason for the low sensitivity observed in cases with low copy number amplification and HER2 heterogeneous expression cases in"human-machine dialogue interpretation."Conclusions:Automatic FISH image analysis and uptake systems simulate the process of manu-ally interpreted cell selection,ensure random cell selection,and improve work efficiency.With its accurate selection of the hybridization re-gion and"human-computer dialogue,"the system is expected to"replace"interpretation by independent pathologists.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Objective To investigate the effect of programmed death ligand-1(PD-L1)overexpression on epithelial mesenchymal transformation(EMT)in endometrial cancer cells and its possible mechanism.Methods Ishikawa/PD-L1,a PD-L1 stable overexpression cell line constructed in the laboratory and the control Ishikawa/EV were used.The efficiency of PD-L1 overexpression was detected by qPCR and Western blot assay.The cell migration ability and invasion activity were detected by scratch assay and Transwell assay.The EMT-related protein and the phosphorylation level of nuclear transcription factor-κB(NF-κB)were detected by Western blot.Results Compared with the control group,the migration ability and invasion activity of Ishikawa/PD-L1 were significantly enhanced,and the expression of E-cadherin was significantly down-regulated,whereas vimentin,N-cadherin and p-p65 were significantly increased.Conclusion PD-L1 can promote EMT by inducing the activation of NF-κB pathway,and thus enhance the migration and invasion ability of endometrial cancer cells.