Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

Progressive family intrahepatic cholestasis （PFIC） is a rare group of autosomal recessive disorders. In recent years， with the development of molecular biology， new pathogenic genes have been constantly identified， and PFIC is currently categorized into 12 genotypes based on the OMIM database. The main manifestations of PFIC include jaundice， pruritus， growth retardation， and malabsorption of fat-soluble vitamins， and some variants can rapidly progress to liver fibrosis， liver cirrhosis， liver failure， and even liver cancer. Different types of PFIC have different clinical manifestations and treatment strategies， and genetic testing can help to achieve early identification and diagnosis. This article reviews the latest advances in the genotyping， clinical features， and treatment of PFIC.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

OBJECTIVES: Through the investigation of the microhardness and microstructure of permanent tooth enamel at various eruption stages during childhood, this research offers references for the early prevention of childhood dental caries. METHODS: Forty-five premolars extracted due to orthodontic reasons were collected and screened. These premolars were divided into three experimental groups according to the time since eruption: Group A (erupted for 0-1 year), Group B (erupted for 1-3 years), and Group C (erupted for 3-5 years). Additionally, the third molars that were extracted due to impaction and had not erupted were selected as the control group, with 15 teeth in each group. Samples were prepared, and the surface microhardness, microstructure, and elemental composition of the enamel were measured using Vickers microhardness tester, scanning electron microscope, and electron probe, respectively. RESULTS: Compared with that in the control group, the microhardness of enamel in groups A, B, and C increased with prolonged eruption time, the surface porosity structure decreased considerably, the contents of Na and Mg on the surface decreased, and that of F increased (P<0.05). CONCLUSIONS The microhardness and microstructure of enamel in permanent teeth at different stages vary. Permanent teeth are at a substantially higher risk of caries within one year after eruption, and early prevention should be emphasized.
Dental Enamel/ultrastructure* ; Humans ; Hardness ; Dental Caries/prevention & control* ; Microscopy, Electron, Scanning ; Tooth Eruption ; Bicuspid/chemistry* ; Dentition, Permanent ; Child ; Child, Preschool

Objective:To describe the current situation of blood glucose control in 18-64 year-old people with type 2 diabetes in the Shenzhen community and analyze the influencing factors to provide a reference for enhancing the management effect of type 2 diabetes in community health service institutions.Methods:The data were from the Shenzhen Community Health Service Information System. A cross-sectional survey design was adopted to include 18-64 year-old patients with type 2 diabetes in Shenzhen community health service institutions in 2022. The blood glucose control rate was calculated through the physical examination data recorded by the information system in 2022, and the influencing factors of blood glucose control in this group of patients were analyzed using a multivariate logistic regression model.Results:A total of 120 174 patients were included in the study. The blood glucose control rate was 53.04%. The results of multivariate logistic regression analysis showed that women ( OR=1.07, 95% CI: 1.04-1.10), ages 45-54 ( OR=1.10, 95% CI: 1.01-1.19), 55-64 ( OR=1.24, 95% CI: 1.14-1.35), middle school ( OR=1.09, 95% CI: 1.05-1.13), high school and technical secondary school ( OR=1.26, 95% CI: 1.21-1.31), junior college or above ( OR=1.75, 95% CI: 1.67-1.83), basic medical insurance for urban employees ( OR=1.05, 95% CI: 1.01-1.08), weekly exercise ( OR=1.26, 95% CI: 1.22-1.31), daily exercise ( OR=1.31, 95% CI: 1.28-1.35) and combined hypertension ( OR=1.21, 95% CI: 1.18-1.24) were more likely to reach the standard of blood glucose control; while unmarried ( OR=0.85, 95% CI: 0.77-0.95), divorced ( OR=0.84, 95% CI: 0.73-0.97), insurance status was fully self-funded ( OR=0.95, 95% CI: 0.91-0.99), disease duration was 5- years ( OR=0.65, 95% CI: 0.63-0.66), ≥10 years ( OR=0.41, 95% CI: 0.39-0.42), the treatment method was diabetes drug therapy ( OR=0.74, 95% CI: 0.71-0.76), low weight ( OR=0.89, 95% CI: 0.80-1.00), obese group ( OR=0.85, 95% CI: 0.82-0.88), combined with central obesity ( OR=0.83, 95% CI: 0.81-0.86), combined with dyslipidemia ( OR=0.69, 95% CI: 0.68-0.71), current smoking ( OR=0.74, 95% CI: 0.72-0.77), and current drinking ( OR=0.97, 95% CI: 0.93-1.00) were less likely to reach the standard of blood glucose control. Conclusions:The blood glucose control rate of 18-64 year-old people with type 2 diabetes in Shenzhen still has room for improvement. More attention should be paid to 18-64 year-old patients with type 2 diabetes, especially for patients with dyslipidemia, central obesity, and diabetes with a long course, and supervision and guidance should be strengthened for patients with bad habits such as smoking, drinking alcohol, and lack of exercise.

Objective:To analyze the disease burden in middle-aged and elderly population aged ≥55 in Shenzhen from 2016 to 2030 and provide evidence for the development of healthy aging strategies.Methods:The years of life lost (YLL), years lost due to disability (YLD), and the disability-adjusted life year (DALY) in this population from 2016 to 2022 were calculated. Joinpoint log-linear regression model was used to analyze the time trend. Bayesian age-period-cohort model and grey system model were used to predict YLL, YLD, and DALY in this population in 2030.Results:From 2016 to 2022, the crude DALY rate showed a transient fluctuation in age group 55-74 years, but a pronounced increase in age group ≥85 years. The proportions of YLL and YLD due to non-communicable diseases in all age groups was considerably higher than those due to communicable and nutritional diseases and injuries. In 2022, in all age groups, the YLL due to neoplasms (55-74 years old) and cardiovascular disease (≥75 years old) ranked first, and the YLD due to musculoskeletal disorder ranked first. By 2030, the causes of YLL and YLD ranking first in each age group would be remained, while the ranks of some causes would increase.Conclusions:The age specific characteristics of current and predicted disease burden differed in individuals aged ≥55 years. Therefore, it is necessary to allocate social and medical resources according to the disease burden pattern.

Background Heavy metal exposure may be associated with the risk of metabolic syndrome (MetS) and serum uric acid. The role of serum uric acid in the relationship between heavy metal exposure and MetS is currently unclear. Objective To evaluate the relationships of heavy metal exposure with MetS and serum uric acid, and to quantify the role of serum uric acid in the relationship. Methods In 2021, convenience sampling was used to select 571 local adults in Liuzhou, Guangxi. Demographic characteristics, lifestyle habits, and physiological and biochemical indicators were collected through questionnaire surveys and physical examinations. Fasting blood and mid-stream morning urine were also collected. The concentrations of 16 heavy metals in urine were measured using inductively coupled plasma mass spectrometry. Least absolute shrinkage and selection operator (LASSO) regression was employed to identify heavy metals associated with MetS. Logistic regression and linear regression models were employed to evaluate the association between the selected heavy metals and MetS as well as serum uric acid. Bayesian kernel machine regression (BKMR) model was utilized to assess the impact of combined exposures to multiple metals on the risk of MetS and identify the main effect metals. Generalized structural equation model was used to evaluate potential mediating effect of serum uric acid on the relationship between heavy metal exposure and MetS. Results The LASSO regression identified a total of 9 heavy metals that were associated with MetS. The logistic regression revealed a positive correlation between zinc and copper in urine and MetS (P _trend<0.05), while vanadium showed a negative correlation with MetS (P _trend<0.05). Compared to the low concentration groups, the high concentration groups of zinc (OR=2.37, 95%CI: 1.33, 4.20) and copper (OR=2.29, 95%CI: 1.26, 4.18) had an increased risk of MetS, while the high concentration group of vanadium showed a decreased risk of MetS (OR=0.47, 95%CI: 0.27, 0.84). The main effect metals identified by the BKMR model were consistent with the results of logistic regression. The linear regression analysis demonstrated an association between urinary zinc and vanadium concentrations and serum uric acid levels (P _trend<0.05). Compared to the low concentration group, the high concentration group of zinc showed an increase in serum uric acid level (β=0.07, 95%CI: 0.03, 0.11), while the high concentration group of vanadium showed a decrease in serum uric acid level (β=-0.06, 95%CI: -0.09, -0.02). The mediation analysis revealed that serum uric acid played a mediating role in the relationship between urinary zinc and vanadium concentrations and MetS, with mediation proportions of 8.33% and 16.67%, respectively. Conclusion Exposure to heavy metals zinc, copper, and vanadium are closely associated with MetS. Zinc and vanadium exposures are correlated with serum uric acid levels, and serum uric acid plays a partial mediating role in the relationship between zinc and vanadium exposures and MetS.