OBJECTIVES: To investigate the effect of pachymic acid on brown/beige adipocyte differentiation and lipid metabolism in preadipocytes. METHODS: 3T3-L1 MBX cells were induced to differentiate into beige adipocytes using a brown cocktail method. The impact of pachymic acid on the viability of 3T3-L1 MBX cells was evaluated using the CCK-8 assay. The formation of lipid droplets following treatment with pachymic acid was observed by oil red O staining. The mRNA expression levels of key browning genes, including uncoupling protein (Ucp) 1, the peroxisome proliferator activated receptor-γ coactivator (Pgc)-1α, and the PR domain-containing protein 16 (Prdm16), as well as the mRNA expression of sterol regulatory element-binding protein (Srebp) 1c, acetyl-coA carboxylase (Acc), fatty acid synthase (Fas), and hormone-sensitive triglyceride lipase (Hsl), adipose triglyceride lipase (Atgl), and carnitine palmitoyltransferase (Cpt) 1 were detected by quantitative reverse transcription polymerase chain reaction. The protein expression of Ucp1, Pgc-1a, and Prdm16 was detected by Western blotting. RESULTS: The 3T3-L1 MBX cells were induced in vitro to form beige adipocytes with high expression of key browning genes(Ucp1, Pgc-1α, and Prdm16), and beige adipose-marker genes (Cd137, Tbx1, and Tmem26). Concentrations range of 0-80 μmol/L pachymic acid were non-cytotoxic to 3T3-L1 MBX cells. Pachymic acid treatment significantly inhibited the differentiation of 3T3-L1 MBX cells, resulting in a notable decrease in lipid accumulation. There was a marked increase in the expression of key browning genes and their proteins products, such as Ucp1, Pgc-1α, and Prdm16, while the expressions of fat synthesis-related genes Srebp1c, Acc and Fas were significantly decreased (all P<0.05). The expressions of lipolysis-related genes (Hsl, Atgl, and Cpt1) were significantly increased (all P<0.05). Treatment with 20 μmol/L pachymic acid showed the most pronounced effect. CONCLUSIONS Pachymic acid can inhibit fat synthesis and promote lipid decomposition by regulating the brown formation and lipid differentiation of preadipocytes.
Animals ; Lipid Metabolism/drug effects* ; Mice ; Cell Differentiation/drug effects* ; Adipocytes, Beige/drug effects* ; 3T3-L1 Cells ; Adipocytes, Brown/drug effects* ; Triterpenes/pharmacology* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Uncoupling Protein 1 ; Sterol Regulatory Element Binding Protein 1/metabolism*

OBJECTIVES: This study aims to investigate the optimal dose ratio and mechanisms of the primary active components in Yinchenhao decoction (geniposide, chlorogenic acid, and rhubarb polysaccharides) for ameliorating metabolic-associated steatotic liver disease (MASLD). METHODS: C57BL/6 mice were randomly divided into the normal control group, model control group, uniform design groups 1-6, and Yinchenhao Decoction group; except for the normal control group, mice in all other groups were fed a Western diet to establish a MASLD model, and after 8 weeks of modeling, mice in the uniform design groups 1-6 and Yinchenhao Decoction group were given the corresponding drugs by gavage. At 12 weeks, all mice were sacrificed: their body weight and liver weight were measured, hematoxylin-eosin staining was used to observe the histopathological changes of liver tissue, the plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected, and the levels of total cholesterol (TC) and triglycerides (TG) in plasma and liver were measured. Based on these results, the optimal uniform design group was identified; subsequently, with plasma AST, plasma TG, and liver TC levels as screening indicators, the optimal dose ratio was obtained via a regression equation, which was further verified from two dimensions, namely functional indicators and tissue morphology. Meanwhile, glucose tolerance test and insulin tolerance test were conducted to evaluate glucose metabolic homeostasis and insulin sensitivity in mice, periodic acid-Schiff staining was used to observe glycogen accumulation, quantitative reverse transcription-polymerase chain reaction was employed to detect the mRNA expression of genes related to glycolipid metabolism and bile acid metabolism, Western blotting was performed to measure the protein expression of molecules involved in bile acid metabolism, and commercial kits were used to determine the plasma levels of total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA). RESULTS: Combinations of geniposide, chlorogenic acid, and rhubarb polysaccharide all reduced the liver-to-body weight ratio, alleviated liver injury, and decreased lipid accumulation, among which the uniform design group 6 (200 mg/kg geniposide+160 mg/kg chlorogenic acid+340 mg/kg rhubarb polysaccharide) exhibited the optimal efficacy. Meanwhile, regression analysis indicated that the dosage ratio of uniform design group 6 was the optimal one for MASLD intervention. Validation experiments showed that, compared with single-drug intervention, the optimal dosage ratio resulted in significantly lower body weight, as well as lower plasma levels of ALT, AST and TC in mice (all P<0.05), along with a more pronounced reduction in the area of hepatic lipid accumulation. Mechanistic investigation experiments demonstrated that intervention with the optimal dosage ratio significantly improved glucose tolerance and insulin sensitivity in mice (all P<0.05), reduced hepatic glycogen deposition, and downregulated the mRNA expression of glycolipid metabolism-related genes such as Gsk3, G6pc, Pck1, Fbp1, Fasn, Srebp-1c, Scd1, Slc27a2, and Slc27a5 (all P<0.05); it also decreased plasma levels of TBIL, DBIL, and TBA (all P<0.05), reversed the abnormal protein expression of bile salt export pump (BSEP), farnesoid X receptor (FXR), and cholesterol-7α-hydroxylase (CYP7A1) in the liver (all P<0.05), and reversed the abnormal mRNA expression of bile acid metabolism-related genes including Nr1h4, Cyp7a1, Cyp27a1, Slc10a1, and Slco1a1 (all P<0.05). CONCLUSIONS The combination of geniposide (200 mg/kg), chlorogenic acid (160 mg/kg), and rhubarb polysaccharide (340 mg/kg) exerts the optimal ameliorative effect on MASLD in mice. This superior efficacy is presumably achieved by synergistically regulating the key nodes of glycolipid metabolism and bile acid metabolism, ultimately optimizing the therapeutic outcome.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To explore high-risk sexual behaviors of HIV/AIDS and related factors in young students in Guangzhou.Methods:A cross-sectional survey was conducted in 5 different types of Guangzhou colleges by convenience sampling with minimum number of classes per grade and 600 samples per school from September to November 2021. The R 4.2.2 software was used to consolidate databases. Simultaneously, a logistic regression model and a decision tree algorithm model, stratifying by whether sexual behaviors had occurred before, were constructed. In each layer, the prediction performance of the two models was evaluated through area under receiver operating characteristic and the confusion matrix, and then the model with high prediction performance was retained.Results:A total of 7 346 students were surveyed. The proportion of the respondents reporting sexual experience were 9.08% (667/7 346), in whom 26.24% (175/667) had risky sexual activity in the past year. The decision tree algorithm model performs well in predicting whether high-risk sexual behaviors have occurred in the past year. When the complexity parameter value is 0.018, and nsplit reaches 4, which means there are 5 leaf nodes in the model, the cross error of the tree will be the smallest. The first best grouping variable in the decision tree was whether to use condoms throughout the first sexual behavior. If condoms were used at their sexual debut, but homosexual practices have occurred in the past year, the probability of risky sexual behavior will increase. If homosexual practices have not occurred in the past year, but the age of sexual debut was below 18 years old while the period of HIV education was after high school, the probability of risk sexual behavior will also increase.Conclusions:AIDS-related risky behaviors of young students still deserved attention. The experience of sexual debut and whether AIDS-related health education has been received before the sexual debut were significant predictors for the occurrence of high-risk sexual behavior. The decision tree algorithm model has particular applicability for predicting and screening potential risk populations.

OBJECTIVE To explore the correlation between changes in intestinal toxicity and changes in component composition of the Mongolian medicine Euphorbiae pekinensis Radix(EPR)before and after processing with milk.METHODS Mice were given 95%ethanol extract of raw EPR,milk-processed EPR and water-processed EPR by gavage.The purgative effect and intestinal inflam-matory toxicity changes of EPR before and after milk processing were investigated using the fecal water content and the levels of inflam-matory factors TNF-α and IL-1β in each intestinal segment of mice as indicators;LC-MS/MS was used to analyze the composition changes of the 95%alcohol extract of EPR before and after milk processing.RESULTS Compared with the blank group,the raw and water processed products of EPR could significantly increase the water content of mouse feces and the levels of TNF-α and IL-1β in each intestinal segment(P＜0.05);compared with the raw product group,all indicators in the milk processing group were significantly reduced(P＜0.05),while there was no significant difference in the water processing group,indicating that water processing cannot at-tenuate toxicity,and the auxiliary material milk is the key auxiliary material to reduce the toxicity of EPR.Mass spectrometry analysis results showed that a total of 50 components were identified in EPR,including 38 terpenoid components,6 phenolic acid components,and 6 other components.The content of each component decreased to varying degrees after milk processing.Principal component analy-sis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were performed on the mass spectrum data of raw ma-terials and products,and it was found that the components of raw materials and products can be obviously clustered into 2 categories.13 differential components of raw materials and products were screened through t test,and 11 of which were terpene compo-nents,indicating that the composition of terpene components changed significantly after milk processing.17 components derived from EPR were detected in the residual liquid of milk excipients after processing,of which 16 were terpenoids,indicating that the terpenoid components of EPR were transferred to the excipient milk during the soaking and processing processes.CONCLUSION The toxicity of EPR is reduced and the purgative effect is alleviated after milk processing.The attenuation mechanism may be that during the milk soaking and processing processes,terpenoid components are transferred to the milk,and the content of toxic components in the decoc-tion pieces is reduced,thereby reducing the toxicity.

OBJECTIVE To optimize the extraction process of polysaccharides from Dendrobium officinale， and preliminarily study its effect on acute lung injury （ALI） in mice. METHODS Using D. officinale as raw material， the polysaccharides were extracted from D. officinale by ultrasonic-assisted hot water immersion. Using the extraction rate of D. officinale polysaccharides as response value， the single-factor experiments and Box-Behnken response surface method were used to optimize the ratio of material to liquid， extraction time and extraction temperature. ALI mice were induced by lipopolysaccharide. Using prednisone acetate （5 mg/kg） as the positive control， the effects on the mass ratio of wet and dry lung and pathological changes of lung tissue （HE staining and Masson staining） of low-dose， medium-dose and high-dose D. officinale polysaccharides （50，100，200 mg/kg） were investigated. RESULTS The optimal extraction technology of D. officinale polysaccharides was as follows： the ratio of material to liquid was 1∶25 （g/mL）， the extracting time was 1 h， and the extracting temperature was 58 ℃ . Under these conditions， the average extraction rate of D. officinale polysaccharides was 37.75% （RSD＝1.12%，n＝3）， the relative error of which with predicted value （38.63%） was 2.28%. Compared with the model group， the ratios of wet and dry lung in the positive control group and D. officinale polysaccharides groups were all decreased significantly （P＜0.05 or P＜0.01）， and the pathological changes in lung tissue （severe destruction of alveolar structure， significant widening of alveolar septa， extensive infiltration of inflammatory cells and proliferation of fibroblasts） were alleviated to varying degrees. CONCLUSIONS The optimal extraction process of D. officinale polysaccharides is feasible； the obtained polysaccharide extract has a certain improvement effect on ALI in mice.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies