OBJECTIVE To investigate the effect and mechanism of modified Lichong decoction （MLCD） on the apoptosis of transplanted tumor cells in nude mice. METHODS Human gastric cancer AGS cells were cultured， and a nude mice transplanted tumor model was established. The nude mice were divided into the model group and MLCD low-， medium- and high-dose groups （150， 300， 600 mg/kg）. They were given distilled water or the corresponding drug solution by gavage once daily for four consecutive weeks. The size of transplanted tumors in nude mice was measured every six days， and the tumor volume was calculated. After the medication， the nude mice were sacrificed， and the transplanted tumor tissues were isolated. The contents of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in the transplanted tumor tissues were detected， and the changes in mitochondrial membrane potential were assessed. The pathological morphological changes were observed. The enzymatic activities of caspase-3， caspase-8， and caspase-9， as well as protein expressions of Fas and FasL and mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL in the transplanted tumor tissues， were detected. RESULTS Compared with the model group， the volume of transplanted tumors in nude mice from all MLCD dose groups was reduced to varying degrees. The contents of LDH and ROS， as well as the enzymatic activities of caspase-3， caspase-8 and caspase-9， were significantly increased/enhanced. The mitochondrial membrane potential was significantly decreased. The protein expressions of Fas and FasL， and the mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL were significantly up-regulated. Most of these differences were statistically significant （ P ＜0.05 or P ＜0.01）. Pathological results showed that with increasing doses of MLCD， the cellular density in the transplanted tumor tissues gradually decreased， and typical morphological features of apoptosis， such as loosening and increasing fragmentation， became more prominent. CONCLUSIONS MLCD can induce apoptosis in transplanted tumor cells of nude mice， and its mechanism may be related to the activation of the Fas/FasL pathway and the caspase apoptotic pathway.

Purpose: In this study, the neural communication patterns between hypothalamic structures and cortical areas in girls diagnosed with central precocious puberty (CPP) were explored. Endocrine profiles were incorporated to clarify the pathophysiological interactions between cerebral networks and hormonal regulation. The hypothalamus was designated as the key focus area for connectivity analysis. Methods: Fifty-seven girls (37 CPP, 20 non-CPP) were recruited from the Pediatric Development Clinic at the Second Affiliated Hospital of Anhui Medical University. The collected data included demographic information, gonadotropin-releasing hormone stimulation tests, and magnetic resonance imaging scans. Hypothalamic functional connectivity (FC) was analyzed using predefined region of interest coordinates, and correlations between hormone levels and FC values were assessed. Results: Compared to the non-CPP group, the CPP group exhibited elevated baseline follicle-stimulating hormone (FSH), baseline luteinizing hormone (LH), peak FSH, peak LH, and peak LH/FSH ratios. Patients with CPP exhibited enhanced neural synchronization linking the right lateral hypothalamic effector zone to the right superior frontal gyrus (displaying a borderline significant correlation with peak LH concentrations), concurrent with diminished functional coupling of the right lateral hypothalamic efferent to the right fusiform/supramarginal gyri. The left lateral hypothalamic projections demonstrated amplified connectivity with the right cuneus. No FC differences were observed in the medial hypothalamus. Conclusion Abnormal lateral hypothalamus FC patterns were identified in CPP girls and were particularly linked to peak LH levels. The findings offer novel insights into the neuroendocrine mechanisms underlying CPP.

Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis. Materials and Methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted. Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases. Conclusion CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

This paper aims to summarize Professor ZHOU Shaohua's clinical experience in treating Parkinson's disease （PD） based on the "disease-symptom-syndrome integration" approach. It is believed that kidney essence deficiency is the root cause of the disease， and phlegm-stasis accumulating toxin is the key factor for its deterioration. PD could be divided into the prodromal stage， early stage and middle-late stage. In the prodromal stage， treatment focuses on tonifying the kidney and replenishing marrow， choosing Zuogui Pill （左归丸） or Yougui Pill （右归丸） to prescribe with modifications according to accompanying non-motor symptoms such as constipation and rapid eye movement sleep behavior disorder. For the early stage， the disease is differentiated into three syndromes， liver-kidney yin deficiency with stirring wind， spleen-kidney yang deficiency， and excessive phlegm turbidity， then following the principle of "calming wind by regulating blood first"， the basic prescriptions of Dading Fengzhu Pill （大定风珠）， Yougui Pill （右归丸） and Jinshui Liujun Decoction （金水六君煎） are applied respectively， combined with Siwu Decoction （四物汤） to nourish blood and extinguish wind. For the middle-late stage， therapies of tonifying the kidney and conso-lidating original qi are combined with detoxifying and resolving turbidity， prescribing fleshy and nourishing medicinals such as deer-horn glue （Cervus nippon Temminck） and turtle shell glue （Colla Carapacis et Plastri Testudinis）， together with Huanglian Jiedu Decoction （黄连解毒汤） to clear heat， detoxify and resolve turbidity， implementing simultaneous tonification and elimination. Integrated traditional Chinese and western medicine intervention is emphasized for non-motor symptoms including orthostatic hypotension and dysphagia.

ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol （Res） via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation， adipocyte browning， and inflammation inhibition， thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases. MethodsThe cell counting kit-8 （CCK-8） assay was adopted to detect the safe and effective doses （7.5， 15， 30 μmol·L^-1） of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes， the cells were assigned into the blank ［treated with dimethyl sulfoxide （DMSO）］ group and the Res （7.5， 15， 30 μmol·L^-1） groups and treated for 48 h. Oil red O staining and total triglyceride （TG） content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay （CETSA） combined with Western blot analysis. Furthermore， the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and mitochondrial uncoupling protein 1 （UCP1）， as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8） and high-mobility group protein B1 （HMGB1） were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green， on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated. ResultsCompared with the control group， Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L^-1， without significantly affecting cell viability. Compared with the control group， different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes （P<0.01）， promoted the expression of NDUFS8 （P<0.01）， increased the ATP concentration and the protein levels of UCP1 and PGC-1α， elevated the level of TNF-α （P<0.05， P<0.01）. ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1， thus inhibiting lipid accumulation and ameliorating obesity.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective:To investigate the protective effect of Dendrobium officinale polysaccharides(DOP)on intestinal mucosal barrier damage,and to elucidate the possible mechanism.Methods:Ten female C57BL/6 mice,aged 5 months,were selected as young group;twenty femal C57BL/6 mice,aged 15 months,were randomly divided into aged group and DOP treatment group(200 mg·kg-1,DOP group),with 10 mice in each group.The mice in DOP group were administrated with DOP by gavage.The body mass,food intakes and hanging time of the mice in various groups were detected.HE staining was used to observe the pathomorphology of intestinal and spleen tissues of the mice in various groups.Immunohistochemical staining was used to detect the expressions of intestinal atresin 1(ZO-1)and Mucin 2(MUC2)in intestinal tissue of the mice in various groups.The intestinal baterial metabolite medium(IBMM)were prepared to intervene the Caenorhabditis elegans(C.elegans),and the C.elegans were randomly divided into Young-IBMM group,Aged-IBMM group,and DOP-IBMM group.Immuno-fluorescence method was used to analyze the intestinal lipofuscin accumulation levels on the 1st day and the 12th day of the C.elegans in various groups.Brilliant blue staining was used to assess the intestinal leakage on the 1st day and the 12th day of C.elegans in various groups.The Caco-2 cells were randomly divided into Young-IBMM,Aged-IBMM and DOP-IBMM groups,and Western blotting method was used to detect the expression levels of ZO-1,Occludin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),phosphorylated myosin light chain(p-MLC),myosin light chain kinase(MLCK)proteins in the Caco-2 cells in various groups.Results:Compared with young group,the body mass of the mice in aged group was increased(P＜0.05),the amount of food intake was decreased(P＜0.05),and the hanging time was decreased(P＜0.05);compared with aged group,the body mass of the mice in DOP group was significantly decreased(P＜0.01),the amount of food intake was increased(P＜0.05),and the hanging time was significantly extended(P＜0.01).The HE staining results showed that compared with young group,the thickness of intestinal mucosa of the mice in aged group became thinner,the goblet cells were reduced,the intestinal villi were disordered with different lengths,a large amount of hemosiderin was found on the surface of the spleen,the cell components in the red medullary were reduced,and the lymphatic sheath and lymphatic nodes around the intra-white pulp artery remained or almost disappeared;compared with aged group,the thickness of the intestinal mucosa of the mice in DOP group was increased,the goblet cells were increased,the length of the intestinal villi was consistent and neatly arranged,the overall function of the red pulp of the spleen was improved,and the components of the white pulp were increased.The immunohistochemical staining results showed that compared with young group,the expression levels of ZO-1 and MUC2 proteins in intestinal tissue of the mice in aged group were significantly decreased(P＜0.05 or P＜0.001);compared with aged group,the expression levels of ZO-1 and MUC2 proteins in the intestinal tissue of the mice in DOP group were significantly increased(P＜0.05 or P＜0.001).The immuno-fluorescence analysis showed that compared with Young-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in Aged-IBMM group was significantly increased(P＜0.001);compared with Aged-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in DOP-IBMM group was significantly reduced(P＜0.001).The brilliant blue staining showed that compared with Young-IBMM group,the bright blue dye leaked into the whole body of C.elegans from intestinal tissue in Aged-IBMM group,and the intestinal structure became blurred and was difficulted to be observed;compared with Aged-IBMM group,the leakage of bright blue dye of C.elegans in DOP-IBMM was reduced.The Western blotting results showed that compared with Young-IBMM group,the expression levels of TNF-α,IL-6,p-MLC,and MLCK proteins in the Caco-2 cells in Aged-IBMM group were significantly increased(P＜0.01 or P＜0.001),and the expression levels of ZO-1 and Occludin proteins were significantly decreased(P＜0.05 or P＜0.01);compared with Aged-IBMM,the expression levels of TNF-α,IL-6,p-MLC and MLCK proteins in the Caco-2 cells in DOP-IBMM group were significantly decreased(P＜0.01),and the expression levels of ZO-1 and Occludin proteins were significantly increased(P＜0.05 or P＜0.01).Conclusion:DOP has an ameliorating effect on intestinal mucosal barrier damage in the aged mice,and its mechanism may be related to the improvement of intestinal barrier damage by regulating intestinal bacterial metabolites,inhibiting the p-MLC/MLCK signal pathway,restoring the expression of tight junction complexes,and reducing the level of intestinal inflammation.

Epicardial adipose tissue(EAT)is a type of fat tissue that is closely adjacent to the coronary arteries and myocardium,and it caused physiological and pathological changes to the body through the secretion of autocrine and paracrine active factors.EAT is regarded as a diagnostic marker and a potential therapeutic target for cardiovascular diseases,and it is of great significance to segment and quantify EAT.This article introduced the evolution of the EAT segmentation and quantification methods from the aspects of traditional imaging,atlas,and artificial intelligence.Furthermore,it reviewed the research progresses on automatically quantified EAT indices in the diagnosis and treatment of cardiovascular diseases.

Objective:To evaluate the cost-effectiveness of Artificial Intelligence(AI)-assisted physician image interpretation in the screening of early-stage lung cancer(stage Ⅰ)from the perspective of the healthcare system,so as to provide evidence for screening strategy optimization.Methods:Based on community populations,a decision tree model was constructed to simulate the cost-effectiveness of two screening strategies:Al-assisted physician image interpretation and independent physician image interpretation,and the Incremental Cost-Effectiveness Ratio(ICER)was calculated.Results:In the basic analysis,the per capita costs of the AI-assisted group and the physician group were 1 483 yuan and 1 489 yuan,respectively,and the effectiveness was 17.02 Quality-Adjusted Life Years(QALYs)and 16.99 QALYs,respectively.Compared with the physician group,the AI-assisted group saved 6 yuan per case and obtained an additional 0.03 QALY per case.The ICER was negative,indicating that the AI-assisted group had an absolute advantage.Threshold analysis showed that when the inspection cost of Al-assisted physician image interpretation increased to 428 yuan per case,the average cost per case was the same between these two groups,and the ICER was 0.When the inspection cost of Al-assisted physician image interpretation was above 428 yuan,the ICER was positive,still demonstrating economic efficiency.Conclusion:AI-assisted image interpretation is cost-effective in the screening of early-stage lung cancer and can facilitate the"early detection,early diagnosis,and early treatment"of lung cancer based on improving the efficiency and accuracy of screening,so as to provide scientific support for health system resource optimization.

The ability to localize sound sources rapidly allows human beings to efficiently understand the surrounding environment. Previous studies have suggested that there is an auditory "where" pathway in the cortex for processing sound locations. The neural activation in regions along this pathway encodes sound locations by opponent hemifield coding, in which each unilateral region is activated by sounds coming from the contralateral hemifield. However, it is still unclear how these regions interact with each other to form a unified representation of the auditory space. In the present study, we investigated whether functional connectivity in the auditory "where" pathway encoded sound locations during passive listening. Participants underwent functional magnetic resonance imaging while passively listening to sounds from five distinct horizontal locations (-90°, -45°, 0°, 45°, 90°). We were able to decode sound locations from the functional connectivity patterns of the "where" pathway. Furthermore, we found that such neural representation of sound locations was primarily based on the coding of sound lateralization angles to the frontal midline. In addition, whole-brain analysis indicated that functional connectivity between occipital regions and the primary auditory cortex also encoded sound locations by lateralization angles. Overall, our results reveal a lateralization-angle-based representation of sound locations encoded by functional connectivity patterns, which could add on the activation-based opponent hemifield coding to provide a more precise representation of the auditory space.
Humans ; Sound Localization/physiology* ; Male ; Female ; Magnetic Resonance Imaging ; Young Adult ; Functional Laterality/physiology* ; Adult ; Brain Mapping ; Auditory Cortex/physiology* ; Acoustic Stimulation ; Auditory Pathways/physiology* ; Brain/physiology*