Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2＜BMI≤23 kg/m2), a group B (23 kg/m2＜BMI≤29 kg/m2) and a group C (BMI＞29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Background and Aims:Obstructive jaundice(OJ)caused by common bile duct stones(CBDS)is a major risk factor for acute cholangitis(AC).Early identification of high-risk patients is essential for improving prognosis.Soluble CD163(sCD163)and milk fat globule epidermal growth factor 8(MFG-E8)are associated with inflammatory diseases,but their predictive value for AC in CBDS-related OJ remains unclear.This study aimed to evaluate the predictive significance of serum sCD163 and MFG-E8 levels for AC in patients with CBDS-OJ.Methods:A total of 142 patients with CBDS-OJ admitted from January 2022 to June 2024 were included as the observation group,and 145 healthy individuals undergoing physical examination served as controls.Serum sCD163 and MFG-E8 levels were measured using ELISA.Based on the occurrence of AC within 24 hours after admission,patients with CBDS-OJ were divided into an AC group(n=48)and a non-AC group(n=94).Clinical variables and serological indicators were compared between groups.Multivariate logistic regression was used to identify independent factors associated with AC.Receiver operating characteristic(ROC)curves were generated to assess the predictive performance of sCD163,MFG-E8,and their combination.Results:Compared with the control group,patients with CBDS-OJ showed significantly elevated serum sCD163 levels and decreased MFG-E8 levels(both P<0.05).Within the observation group,the AC group had higher AST,ALT and sCD163 levels and lower MFG-E8 levels than the non-AC group(all P<0.05).Logistic regression identified elevated sCD163 as an independent risk factor(OR=3.478,P<0.001)and reduced MFG-E8 as a protective factor(OR=0.526,P=0.020)for AC.ROC analysis showed AUC values of 0.759 for sCD163,0.787 for MFG-E8,and 0.920 for their combined detection,with the combined model outperforming either marker alone(P<0.001).Conclusion:Serum sCD163 elevation and MFG-E8 reduction are closely associated with the development of AC in patients with CBDS-OJ.Combined detection of sCD163 and MFG-E8 provides superior predictive value and may serve as a useful tool for early risk stratification in clinical practice.

Objective:Non-targeted metabolomics based on ultra-performance liquid chromatography mass spectrometry(UPLC-MS)platform was used to study the metabolic characteristics of multiple myeloma(MM)patients,and explore potential new metabolic mechanisms affecting the occurrence and development of MM.Methods:The study enrolled 42 MM patients,including 21 newly diagnosed(ND)patients and 21 relapsed patients(RP),and 21 age-sex matched healthy controls(HC)as subjects.UPLC-MS analysis platform was used to detect small molecule metabolites in serum of the subjects.Principal component analysis(PCA),orthogonal partial least-squared discriminant analysis(OPLS-DA)and 200 random permutations were used to analyze the differences of metabolic profiles among groups.Identification of differential metabolites was completed in the Human Metabolome Database(HMDB)and abnormal metabolic pathway analysis was performed using the KEGG database.Results:The metabolic profiles of MM patients and healthy controls were significantly separated in both PCA and OPLS-DA models,while the metabolic profiles of newly diagnosed and relapsed MM patients were significantly separated only in OPLS-DA model.In ND vs HC,RP vs HC and RP vs ND cohorts,19,24 and 18 differential metabolites were identified respectively,mainly sphingolipids,glycerophospholipids and fatty acyl amino acids.The metabolic pathway abnormalities in newly diagnosed and relapsed MM patients were mainly manifested in sphingolipid metabolism and glycerophospholipid metabolism compared to healthy controls.Compared with newly diagnosed MM patients,relapsed MM patients were mainly manifested in sphingolipid metabolism and ether-lipid metabolism.Conclusion:The metabolic profiles of MM patients are significantly different from those of healthy people.Relapsed MM patients and newly diagnosed MM patients have similar metabolic profiles,but there are still some differences.Glycerophospholipid metabolism,sphingolipid meta-bolism and ether-lipid metabolism may play important biological roles in the occurrence and development of MM.

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

OBJECTIVE: miR-34c-3p is down-regulated in nasopharyngeal carcinoma (NPC). The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study. METHODS: Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86 (CD86) and cluster of differentiation 206 (CD206) expression; quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed to examine mRNA expression and protein levels; cell counting kit-8 (CCK8) and transwell assays were employed to assess cell proliferation, migration, and invasion; and hematoxylin-eosin (HE) staining was employed to assess pathological changes in tumor tissues. RESULTS: Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11, and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation, migration, and invasion of NPC cells. The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues. CONCLUSION This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.
MicroRNAs/metabolism* ; Nasopharyngeal Carcinoma/genetics* ; Humans ; Animals ; Nasopharyngeal Neoplasms/genetics* ; Macrophages/physiology* ; Cell Line, Tumor ; Mice ; Cell Proliferation ; Mice, Inbred BALB C ; Cell Movement ; Male ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Female

To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

Background and Aims:Obstructive jaundice(OJ)caused by common bile duct stones(CBDS)is a major risk factor for acute cholangitis(AC).Early identification of high-risk patients is essential for improving prognosis.Soluble CD163(sCD163)and milk fat globule epidermal growth factor 8(MFG-E8)are associated with inflammatory diseases,but their predictive value for AC in CBDS-related OJ remains unclear.This study aimed to evaluate the predictive significance of serum sCD163 and MFG-E8 levels for AC in patients with CBDS-OJ.Methods:A total of 142 patients with CBDS-OJ admitted from January 2022 to June 2024 were included as the observation group,and 145 healthy individuals undergoing physical examination served as controls.Serum sCD163 and MFG-E8 levels were measured using ELISA.Based on the occurrence of AC within 24 hours after admission,patients with CBDS-OJ were divided into an AC group(n=48)and a non-AC group(n=94).Clinical variables and serological indicators were compared between groups.Multivariate logistic regression was used to identify independent factors associated with AC.Receiver operating characteristic(ROC)curves were generated to assess the predictive performance of sCD163,MFG-E8,and their combination.Results:Compared with the control group,patients with CBDS-OJ showed significantly elevated serum sCD163 levels and decreased MFG-E8 levels(both P<0.05).Within the observation group,the AC group had higher AST,ALT and sCD163 levels and lower MFG-E8 levels than the non-AC group(all P<0.05).Logistic regression identified elevated sCD163 as an independent risk factor(OR=3.478,P<0.001)and reduced MFG-E8 as a protective factor(OR=0.526,P=0.020)for AC.ROC analysis showed AUC values of 0.759 for sCD163,0.787 for MFG-E8,and 0.920 for their combined detection,with the combined model outperforming either marker alone(P<0.001).Conclusion:Serum sCD163 elevation and MFG-E8 reduction are closely associated with the development of AC in patients with CBDS-OJ.Combined detection of sCD163 and MFG-E8 provides superior predictive value and may serve as a useful tool for early risk stratification in clinical practice.