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.

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.

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 This study aimed to explore the relationship between the spontaneous changes of mesiodistal angulation of lower second molars(L2M)and individual clinical characteristics in patients with early permanent dentition correction.Methods A total of 44 patients with a total of 88 mandibular second molars were included in this study after screening.Based on the frequency distribution histogram of the initial angle of inclina-tion(L2M initial angle)of the L2M crown before treatment,it was divided into three groups:Group A:small angle group,L2M initial angle is 0°～17.5°;Group B:medium angle group,L2M initial angle is 17.5°～42.5°;Group C:large angle group,L2M initial angle is 42.5°～60°.According to whether L2M has erupted and exposed most of the crown,it was divided into erupted group and unerupted group.According to the mandibular plane angle,it can be divided into high angle,low angle,and average angle.CBCT reconstructed panoramic images were used to measure the mesiodistal inclination of L2M and analyze the relationship between each group and the change in mesiodistal inclination angles of L2M.Results After treatment,L2M mesiodistal angulation in the small angle,large angle,non-eruption,and high angle groups became more significant.The angle in the middle angle group was significantly smaller.The L2M mesiodistal angulation in the eruption and average angle group did not change significantly.The angles of ANB,Y-axis,and mandibular plane have no correlation with the initial angle of L2M.Conclusion The L2M in patients with large and high angles is more likely to topple during a correc-tion.During the correction,the L2M tends to approach the normal axial inclination.

Purpose To study the expression of of mono-clonal and polyclonal TRPS1 antibodies in synovial sarcoma,and to explore the value of TRPS1 in the diagnosis and differen-tial diagnosis of synovial sarcoma and the sensitivity and speci-ficity of polyclonal TRPS1 for the diagnosis of synovial sarcoma.Methods Immunohistochemical EnVision method was used to detect the expression of monoclonal and polyclonal TRPS1 anti-bodies in the synovial sarcomas and its mimickers.Results A-mong 31 cases of synovial sarcoma,the positive rates of poly-clonal and monoclonal TRPS1 antibodies were 54.8％and 93.5％,respectively.Of 30 synovial sarcoma mimicking le-sions,2 were positive for TRPS1(polyclonal antibody),which was 6.67％,and TRPS1 was more frequently expressed in syno-vial sarcoma than in non-synovial sarcoma(P＜0.05).The sensitivity of polyclonal TRPS1 antibody for the diagnosis of syn-ovial sarcoma was 93.5％,and the specificity was 93.3％.Conclusion Polyclonal TRPS1 antibody has a higher sensitivity and specificity for the diagnosis of synovial sarcoma and it there-fore is recommended in routine pathologic diagnosis.

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.