Chronic liver diseases with common causes including viral infections， alcohol abuse， and autoimmune diseases. Alkaloids， as a class of plant-derived compounds， have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis， inflammatory response， oxidative stress， and cell apoptosis， and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways， thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases， in order to provide new ideas and directions for the treatment of chronic liver diseases.

OBJECTIVE To establish the fingerprint of Pinghuo tea standard decoction and a method for determination of multi-component to clarify the transfer relationship of quantities and quality from pieces and standard decoction. METHODS Fifteen batches of Pinghuo tea standard decoction were prepared and the extract rate was determined； the fingerprint of the preparation was established by using high-performance liquid chromatography（HPLC）； the similarity evaluation and the determination of common peaks were performed， and chemometric analysis was performed； the same method was used to determine the content of indicator components and the transfer rate was calculated. The chromatographic column was Venusil C18 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution （gradient elution）； the column temperature was 30 ℃， and the detection wavelengths were 238 nm （0-37 min， 85-102 min） and 330 nm （37-85 min） at a flow rate of 1.0 mL/min with an injection volume of 10 μL. RESULTS The similarity of HPLC fingerprints for 15 batches of Pinghuo tea standard decoction was not lower than 0.968. A total of 24 common peaks were calibrated and 9 peaks were recognized， which were as follows neochlorogenic acid （peak 3）， chlorogenic acid （peak 6）， geniposide （peak 9）， glycyrrhizin （peak 10）， galuteolin （peak 11）， isochlorogenic acid A （peak 14）， luteolin （peak 21）， kaempferol （peak 23） and glycyrrhizic acid （peak 24）. Cluster analysis， principal component analysis and orthogonal partial least squares discriminant analysis showed consistent results， all of which could classify the 15 batches of samples into three categories. The linear range of indicator components in 15 batches of Pinghuo tea standard decoction， such as geniposide， luteolin， isochlorogenic acid A， glycyrrhizin， and glycyrrhizic acid， were 0.020 580-0.411 600， 0.001 617-0.080 850， 0.006 076-0.607 600， 0.005 125-0.071 740， and 0.017 288-0.432 200 mg/mL， respectively； RSDs of precision， repeatability， stability and recovery rate tests were all not higher than 4% （n＝6）. The mass fractions ranged 3.227 9-10.002 2， 0.297 4-0.554 6， 3.350 1-6.159 6， 0.720 6-1.073 3， 2.003 1-3.030 1 mg/g； transfer rates from the pieces and standard decoction were 19.762 8%-35.840 5%， 12.123 3%-21.254 0%， 46.097 2%-82.869 4%， 58.708 8%-91.629 6%， 39.114 3%-63.710 6%. The transfer rates of the extract from 15 batches of Pinghuo tea standard decoction ranged from 61.15%-84.68%. CONCLUSIONS Established HPLC fingerprint and content determination methods in this study are simple and accurate， which can provide reference for the quantitative value transfer study， quality control， clinical application and the development of subsequent formulations of Pinghuo tea standard decoction.

Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

The ethics committee of organ transplantation technology and clinical application in a hospital has encountered some difficulties and typical cases in its review work and practice for many years. Sometimes, it is difficult to make a decision in these dilemmas. Based on the previous experience of the hospital in the ethical review of organ donation and transplantation, combined with two typical cases, this paper discussed and analyzed two review points of whether the voluntary unpaid donation and the principle of informed consent were met, and whether the risk-benefit ratio was reasonable, and put forward relevant ethical and legal countermeasure for further research by institutional ethics committees and other parties, in order to provide reference for discussing the practical problems and ethical confusion of ethical review of organ donation and transplantation.

AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

The "four-in-one" approach is based on the four-dimensional perspective of "property, position, tendency and syndrome", which helps to identify and analyze classical prescriptions in a multi-dimensional and three-dimensional way. The early pathogenesis of chronic heart failure (CHF) is deficiency of heart Qi and heart Yang and disorder in Qi transformation in triple energizer, while in the later stage of the disease, it progresses from deficiency to excess, with simultaneous occurrence of deficiency and excess syndromes. Fuling Guizhi Baizhu Gancao Decoction (Linggui Zhugan Decoction) plays its role in treating chronic heart failure by the four elements of "property, position, tendency and syndrome". Property—Linggui Zhugan Decoction is pungent, sweet, slight sweet and bitter in flavor, but warm in property. The sweet is able to tonify deficiency; the pungent is responsible for dispersing Yang, promoting Qi and draining water retention; the warm nourishes the spleen, raises Yang Qi and resolves phlegm; the bitter could excrete diuresis and dry dampness to guarantee the smooth operation of three energizer. Position-Linggui Zhugan Decoction acts on the heart, spleen and triple energizer. It can stimulate heart Yang, strengthen the spleen, resolve phlegm, and regulate the waterways to promote the Qi transformation in triple energizer. Tendency-The tendency of Linggui Zhugan Decoction is upward and downward in parallel, both internal and external. Warming up and promoting diuresis, raising Yang up and tonifying deficiency, it is conducive to the Yang Qi transformation in triple energizer. Syndrome-Linggui Zhugan Decoction is indicated for the syndrome of heart Yang deficiency and water-fluid retention, which begins with the upper abdomen swelling, Qi rushes against the chest. It is widely used in the treatment of water-vapor impulse heart disease. The disorder of Qi transformation in triple energizer is the main mechanism of recurrent CHF. Linggui Zhugan Decoction can not only warm the fire of Qi transformation in triple energizer, but also smooth the pathway of Qi transformation in triple energizer, which is compatible with the treatment of systemic fluid retention in chronic heart failure. Its pharmacological mechanisms include anti-inflammation, anti-platelet aggregation, regulation of cardiomyocyte cell membrane ion channels, protection against ischemia-reperfusion injury and modulation of vasodilation, etc. Deconstructing Linggui Zhugan Decoction with "four-in-one" approach and discussing its mechanism for treating CHF in combination with the theory of "Qi transformation in triple energizer", have great significance to rejuvenate the vitality of classical prescriptions and to apply them accurately and effectively.

This study delineated the conceptual framework of Diagnostic and Treatment Difficulty(DTD)for disease categories for the first time and calculated the coefficient by utilizing disease occurrence probability,average total cost,and cure/improvement rate.The study employed the 2017 data from the New Rural Cooperative Medical Insurance in seven counties or districts to assess the DTD coefficient of inpatient disease categories.It also generated a distribution chart and fitted curve illustrating the relationship between the number of cases and DTD coefficient,in line with disease occurrence patterns.A paired sample Wilcoxon rank-sum test was performed on the DTD coefficient of the same disease categories calculated for two sample counties,yielding non-significant results(p =0.73).This suggests that the algorithm is robust and effectively portrays the occurrence and distribution patterns of disease categories.The measurement results can be utilized to define the scope of disease categories in healthcare institutions and characterize healthcare service supply and demand behavior.However,it's worth noting potential limitations,including a reliance on sample size and subjectivity in weight determination.

Objective:To observe the changes of pelvic floor structure and function in female vaginal laxity after CO 2 fractional laser transvaginal treatment. Methods:This study reviewed the improvement of pelvic floor structure and function after CO 2 fractional laser transvaginal treatment in 28 female patients [aged 26-59 (37.5±8.3) years] with vaginal laxity syndrome seen at the Department of Dermatology, the First Affiliated Hospital of Air Force Medical University from March 2020 to November 2021. A total of 28 female patients with vaginal laxity syndrome underwent intravaginal treatment by CO 2 fractional laser instrument once/month for 3 times. The clinical efficacy and safety were evaluated according to the pre- and post-treatment transverse vaginal diameter, FSFI score of female sexual function, VHIS score of vaginal environment, vaginal tactile imaging system (VTI), pelvic ultrasound and MRI, tissue biopsy, patient satisfaction, pain score, and postoperative adverse effects. Results:Twenty-one of the twenty-eight female patients with vaginal laxity syndrome showed significant improvement in symptoms related to vaginal laxity syndrome after intravaginal treatment with CO 2 fractional laser therapy. All patients showed improvement in all indexes before and 1 month after treatments the mean vaginal transverse diameter decreased from (3.00±0.39) fingers to (2.71±0.40) fingers ( P<0.05), VHIS increased from (17.12±3.97) to (21.69±3.61) ( P<0.05), FSFI score improved from (23.11±3.70) to (27.43±5.33) ( P<0.05), and VTI examination showed that vaginal muscle strength and elasticity were improved to different degrees, and there was a statistical difference compared with that before treatment (total contractility of the anterior vaginal wall: t=26.23, P<0.001; total contractility of posterior vaginal wall: t=39.02, P<0.001; the mean contractility of the anterior vaginal wall: t=17.92, P<0.001; the mean contractility of the posterior vaginal wall: t=22.57, P<0.001). At the same time, questionnaire score of international consultation on incontinent questionnaire short form (ICI-Q-SF scale) of 13 patients with combined mild to moderate stress urinary incontinence showed a statistically significant decrease compared with those before treatment (8.97±2.99 before treatment and (7.18±1.79) one month after treatment; t=2.792, P<0.01). Pelvic ultrasound and magnetic resonance examination indicated a tightening of the vaginal wall structure, and pelvic ultrasound observed a significant decrease in bladder neck mobility and a significant decrease in vesicourethral rotation angle. Vaginal tissue biopsy indicated an increase in the thickness of the vaginal mucosa and an increase in the number and more regular arrangement of collagen fibers after treatment. All patients had high treatment satisfaction and there were no adverse effects such as infection and bleeding during the treatment. Conclusions:Transvaginal CO 2 fractional laser treatment can improve the pelvic floor structure and function around the vagina, treat female vaginal laxity syndrome, stress urinary incontinence and female sexual dysfunction, with significant clinical efficacy and good safety.

Objective To identify the current research hotspots of global health training, and construct a global health talent training evaluation index system. Methods Publications pertaining to global health talent training evaluation were retrieved in China National Knowledge Infrastructure, Wanfang Database, and Web of Science Core Collection from 2003 to 2022, and keywords were extracted from eligible publications for co-occurrence and cluster analyses using the CiteSpace software. Based on keywords clustering results, a global health talent training evaluation index system was constructed using a context, input, process, and product (CIPP) evaluation model as a theoretical framework. Results A total of 692 Chinese publications and 1 264 English publications were included. Keyword co-occurrence and cluster analyses yielded 10 Chinese and 10 English keyword clusters, and the 10 Chinese keyword clusters included analytic hierarchy process, health diplomacy, personnel structure, crossdiscipline, educational assessment, global health discipline development, training needs, curriculum program, quality evaluation and logistics support, while the English keyword clusters included evidence-based practice, capacity building, global health, quality of life, machine learning, leadership, sub-Saharan Africa, health equity, global health security and global health diplomacy. Based on keyword clustering, a global health talent training evaluation index system was constructed with CIPP as the theoretical framework, which contained 4 primary indicators, 15 secondary indicators and 59 tertiary indicators, and the primary indicators included 4 dimensions of context evaluation, input evaluation, process evaluation and product evaluation. Conclusions A global health talent training evaluation index system has been constructed, which provides an effective evaluation tool and quantitative evidence for future global health talent training.