ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

AIM: To explore the therapeutic effect and prognosis of intense pulsed light combined with pralprofen eye drops for meibomian gland cysts in children. METHODS: Children with meibomian gland cysts visited the hospital for treatment from April 2023 to October 2024 were selected as the research subjects. All subjects were grouped using the random number table methed. In the control group, patients were treated with hot compress. In the drug group, patients were treated with pralprofen eye drops combined with hot compress. In the laser group, patients were treated with intense pulsed light combined with hot compress. In the combination group, patients were treated with pralprofen eye drops combined with intense pulsed light and hot compress. The treatment effective rate, cyst surface area, ocular symptom score, and occurrence of adverse reactions of children in each group were compared. RESULTS: A total of 80 children(80 eyes)were enrolled in this study, with 20 cases(20 eyes)in each of the control group, drug group, laser group, and combination group. The mean age was 7.49±1.09 y in the control group(9 males and 11 females), 7.63±0.98 y in the drug group(11 males and 9 females), 7.39±0.59 y in the laser group(12 males and 8 females), and 7.63±1.21 y in the combination group(12 males and 8 females). The total effective rate was 70%(14/20)in the combination group, which was significantly higher than that in the control group, drug group, and laser group(all P<0.05). After treatment, the cyst surface area and ocular symptom scores decreased to varying degrees in all groups. Notably, at 21 d post-treatment, the cyst surface area and ocular symptom scores in the combination group were significantly lower than those in the control group, drug group, and laser group(all P<0.05). No adverse reactions occurred in the combination group, which was lower than that in the control group, drug group, and laser group, with no statistically significant difference among the four groups(P>0.05).CONCLUSION: Intense pulsed light combined with pralprofen eye drops can improve the ocular symptoms of children with meibomian gland cysts, reduce the surface area of meibomian gland cysts, increase the clinical cure rate, and this treatment method is highly safe.

Drug resistance is one of the key factors affecting the effectiveness of cancer treatment methods, including chemotherapy, radiotherapy, and immunotherapy. Its occurrence is related to factors such as mRNA expression and methylation within cancer cells. If drug resistance in patients can be accurately identified early, doctors can devise more effective treatment plans, which is of great significance for improving patients' survival rates and quality of life. Cancer drug resistance prediction based on artificial intelligence (AI) technology has emerged as a current research hotspot, demonstrating promising application prospects in guiding clinical individualized and precise medication for cancer patients. This review aims to comprehensively summarize the research progress in utilizing AI algorithms to analyze multi-omics data including genomics, transcriptomics, epigenomics, proteomics, metabolomics, radiomics, and histopathology, for predicting cancer drug resistance. It provides a detailed exposition of the processes involved in data processing and model construction, examines the current challenges faced in this field and future development directions, with the aim of better advancing the progress of precision medicine.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Objective:To investigate the influencing factors for dysphagia in the elderly,to construct a predictive model for dysphagia,and to provide a theoretical basis for clinical practice.Methods:In this case-control study,the patients with dysphagia who attended Department of Geriatrics in the first affiliated hospital of Chongqing Medical University from March 2016 to June 2023 were enrolled as case group,and the patients without dysphagia who attended the same department during the same period of time were enrolled as con-trol group.The correlation analysis,least absolute shrinkage and selection operator(LASSO)regression,and multivariate logistic re-gression analysis were used to investigate the influencing factors for dysphagia;the 10-fold cross-validation Extreme Gradient Boosting(XGBoost)model was used to predict dysphagia,and the SHapley additive exPlanations(SHAP)method was used for model visualiza-tion.Results:There were 1009 cases in the case group and 2125 cases in the control group.The correlation analysis and LASSO re-gression analysis identified 12 factors for the multivariate logistic re-gression analysis,and the results showed that sarcopenia,increasing age,children or caretakers as caregivers,frail health,poor oral health,poor self-care ability,depression,and cognitive impairment were risk factors for dysphagia(odds ratio[OR]>1,P<0.05),and fe-male sex and participation in community activities were protective factors against dysphagia(OR<1,P<0.05).The XGBoost model had a good predictive efficacy,with an accuracy rate of 0.795,a preci-sion rate of 0.711,a sensitivity of 0.613,a specificity of 0.881,an F1 value of 0.661,and an area under the ROC curve of 0.855.The SHAP plot showed that the top five important characteristics were caregiver,oral score,frail health condition,activities of daily living,and cognitive function.Conclusion:There are various influencing factors for dysphagia in the elderly,and the elderly patients with poor oral health,frailty,dependence on others for daily life,and cognitive impairment should be taken seriously in clinical practice.The XGBoost model has a good performance in predicting dysphagia in the elderly,which can provide a reference for clinical practice.

Objective To analyze the diagnostic value of serum biomarkers in patients with pulmonary tuberculosis complicated by invasive pulmonary aspergillosis.Methods A retrospective collection of laboratory test results,including blood analysis,liver function,lymphocyte counts,and cytokine levels,from 54 patients diagnosed with pulmonary tuberculosis and invasive pulmonary aspergillosis admitted to the Third People's Hospital of Kunming between January 2021 and May 2024.Additionally,70 patients with simple pulmonary tuberculosis and 50 healthy individuals were collected as control groups to compare serum biomarker levels across the three groups and analyze relevant factors and diagnostic value for pulmonary tuberculosis patients with invasive pulmonary aspergillosis.Results Among different age groups,the incidence of pulmonary tuberculosis with invasive pulmonary aspergillosis was 29 cases(53.7％)in youth,15 cases(27.8％)in middle age,and 10 cases(18.5％)in the elderly.In terms of gender distribution,there were 41 males(75.9％)and 13 females(24.1％).The serum levels of CRP(6.85[2.10,27.0])ng/L,PCT(0.05[0.05,0.15])ng/mL,RBC(4.55±0.65)× 1012/L,Hb(129.13±19.10)g/L,TP(66.23±6.82)g/L,ALB(37.03±4.77)g/L,and CHOL(4.30[3.71,4.91])mmol/L in the invasive pulmonary aspergillosis group showed no significant difference compared to the simple tuberculosis group and healthy control group(P＞0.05).The levels of CD3+T,CD4+T,and CD8+T in the invasive pulmonary aspergillosis group were significantly lower than those in the simple tuberculosis group and healthy control group(P＜0.05).The levels of IL-2,IL-4,IL-5,IL-8,IL-10,IL-12p70,IFN-α,and TNF-α in the invasive pulmonary aspergillosis group were significantly higher than those in the healthy control group(P＜0.05);IL-8,IL-12p70,and IFN-α were also higher compared to the simple tuberculosis group,with statistical significance(P＜0.05).Conclusion The population with pulmonary tuberculosis complicated by invasive pulmonary aspergillosis is predominantly male and younger.The serum indicators of infection severity and nutritional status in these patients are similar to those with simple tuberculosis and lack specificity;however,their immune function is significantly lower than that of simple tuberculosis patients.Multiple cytokines are elevated,particularly IL-8,IL-12p70,and IFN-α,which can aid in the differential diagnosis of pulmonary tuberculosis infection.

Inflammatory bowel disease(IBD)is a chronic and recurrent intestinal disease,and has become a major global health issue.Individuals with IBD face an elevated risk of developing colorectal cancer(CRC),and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC.This review covers the pathogenesis of IBD and CRC,focusing on mitochondrial dysfunction,and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function.Additionally,recent advancements in the phar-macological modulation of mitochondrial dysfunction for treating IBD and CRC,encompassing mitochondrial damage,release of mitochondrial DNA(mtDNA),and impairment of mitophagy,are thoroughly summarized.The review also provides a systematic overview of natural compounds(such as flavonoids,alkaloids,and diterpenoids),Chinese medicines,and intestinal microbiota,which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function.In the future,it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function,which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Objective : To analyze the relationship between tongue volume, tongue position, dental and skeletal parameters in adult patients with different skeletal malocclusions, providing references for the etiology, diagnosis, and treatment of skeletal malocclusions. Methods: This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Cone-beam computed tomography (CBCT) and cephalometric radiographs were collected from 60 adult patients, divided into three groups based on ANB angle values: skeletal Class I (0° < ANB < 4°), II (ANB > 4°), and III (ANB < 0°), with 20 cases in each group. Dental and skeletal parameters were measured using Dolphin software. Mimics software was used for 3D reconstruction of the tongue, oral cavity, and upper airway to measure tongue position, tongue volume, oral cavity volume, and upper airway volume, followed by statistical analysis. Results: The skeletal Class III group had significantly larger tongue and oral cavity volumes than the skeletal Class I and Class II groups (P = 0.02). Tongue length in the skeletal Class III group was also greater than in the skeletal Class I and Class II groups (P = 0.016). There was no significant difference in the ratio of tongue volume/oral cavity capacity among the three skeletal malocclusion groups (P > 0.05). Tongue volume was positively correlated with U1-SN and negatively correlated with overbite and overjet (P < 0.05). Additionally, tongue volume showed a significant positive correlation with Go-Gn and Pg-Np (P < 0.01), as well as with maxillary and mandibular dental arch width and basal bone arch width (P < 0.01). Upper airway volume was positively correlated with TT-VRL and TP-VRL (P < 0.05). Conclusion Patients with skeletal Class III malocclusion have larger tongue volumes and longer tongues. Patients with larger tongue volumes may also have larger, more forward-positioned mandibles. Patients with more posterior tongue positions may have smaller upper airway volumes. When developing orthodontic or orthognathic treatment plans, it is crucial to consider the relationship between tongue position, tongue volume, the jaws, and the airway to ensure optimal outcomes for both dental and orofacial function.

Objective:To analyze the epidemiological characteristics and survival rate of nasopharynx cancer (NPC) in Guangdong Province from 2011 to 2019.Methods:Based on the cancer registry data of Guangdong Province from 2011 to 2019, the crude rate, age-standardized rate (the standard population was the fifth Chinese national census of 2000) and age-specific rate of incidence and mortality of NPC were calculated, and the regional distribution characteristics were also explored. The average annual percentage change (AAPC) of the incidence and mortality rates were analyzed by using Joinpoint regression model. The observed survival rate was estimated by period survival method, and the expected survival rate was calculated by Ederer Ⅱ method.Results:The crude incidence rate and age standardized incidence rate of NPC showed a decreasing trend, and the AAPC was -1.9% and -2.1%, respectively ( P＜0.05). The crude mortality rate and age standardized mortality rate of NPC also showed a decreasing trend, and the AAPC was -4.8% and -4.6%, respectively ( P＜0.05). The incidence and mortality rates are both higher in men than those in women during the nine years. The age-specific incidence rate of NPC reached its peak in the 50-64 years old age group, and the mortality rate reached its peak in the 65-74 years old age group in Guangdong province. In 2019, the age-standardized incidence rate of NPC was 9.49/100 000 (13.89/100 000 in men and 5.19/100 000 in women). The incidence and mortality of NPC varied greatly among different areas, and the areas with highest incidence and mortality rate were both in Zhaoqing. In 2020, the five-year observed survival rate of NPC in Guangdong Province was 67.2%, the 5-year relative survival rate was 75.3% and the 5-year standardized relative survival rate was 68.9%. Conclusions:Both the incidence and mortality rates of NPC in Guangdong province show decreasing trend, and the decreasing level of the mortality rate is higher than that of the incidence rate, but the two rates are still at high levels. The prevention and control work should focus on male, middle-aged and elderly population and Zhaoqing, Zhongshan, Foshan areas.