Idiopathic pulmonary fibrosis(IPF) is a chronic progressive interstitial lung disease characterized by a complex pathogenesis and limited treatment options. Although studies have indicated that lipid metabolism dysregulation is associated with the progression of IPF, the core regulatory mechanisms remain unclear. By integrating RNA sequencing data from the GEO database, we identified four key genes related to lipid metabolism: peroxisome proliferator-activated receptor gamma(PPARG), secreted phosphoprotein 1(SPP1), caspase 3(CASP3), and platelet endothelial cell adhesion molecule 1(PECAM1). Further validation using single-cell RNA sequencing revealed the cell-specific expression patterns of these genes. The results found that PPARG was significantly downregulated in alveolar macrophages while SPP1 was significantly upregulated. Mechanistic studies indicated that PPARG negatively regulated SPP1 expression, and the interaction between SPP1 and cluster of differentiation 44(CD44) activated intercellular signaling pathways that promoted fibrosis. Through network pharmacology and molecular docking, it was predicted that the bioactive components of the traditional Chinese medicine formula, namely Buyang Huanwu Decoction may target PPARG to modulate lipid metabolism pathways. In a bleomycin-induced rat model with IPF, this paper randomly divided the rats into six groups(control, group, model group, pirfenidone group, and low, middle, and high-dose groups of Buyang Huanwu Decoction). The results demonstrated that Buyang Huanwu Decoction treatment significantly improved tissue pathological damage, reduced collagen deposition, and alleviated lipid metabolism dysregulation. Western blot analysis confirmed that Buyang Huanwu Decoction mediated the upregulation of PPARG and inhibited the activation of the SPP1/CD44 pathway. The multi-omics study elucidated the role of the PPARG/SPP1/CD44 pathway as a key regulatory factor in lipid metabolism in IPF, providing evidence that Buyang Huanwu Decoction exerted its antifibrotic effects through this novel mechanism and thus offering new insights into the therapeutic prospects for IPF.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; PPAR gamma/genetics* ; Humans ; Osteopontin/genetics* ; Lipid Metabolism/drug effects* ; Idiopathic Pulmonary Fibrosis/genetics* ; Hyaluronan Receptors/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Molecular Docking Simulation

OBJECTIVE: To investigate the clinical efficacy of thoracoscopic minimally invasive surgery with nickel-titanium shape memory alloy wrap bone plate versus rib periosteal internal fixation in patients with multiple rib fractures (MRF) and flail chest. METHODS: A retrospective analysis was performed on 100 patients with MRF and flail chest treated with thoracoscopic minimally invasive surgery and internal fixation with rib fracture preservation between January 2019 and December 2022, including 54 males and 46 females, aged from 20 to 65 years old, with an average age of (38.0±18.0)years old. The duration of the disease ranged from 8 to 21 days. According to the different surgical methods, the patients were divided into control group and study group, with 50 patients in each group. The control group consisted of 23 males and 27 females, with an average age of (38.35±18.05) years old, who underwent rib preservation periosteal internal fixation. In the study group, there were 31 males and 19 females, with an average age of (38.15±17.99) years old, treated with thoracoscopic nickel-titanium shape memory alloy circumferential bone plate. The pulmonary function indices, electrocardiographic monitoring indices, pain severity, levels of inflammatory factors, complications, rehabilitation indices, and therapeutic efficacy were compared between the two groups before and after treatment. RESULTS: All patients were followed up for 6 months. After 3 days of treatment, the heart rate of both groups was (102.43±13.74) beats per minute vs (86.26±8.06) beats per minute, respiratory rate (28.45±3.40) breaths per minute vs (22.05±2.85) breaths per minute, blood oxygen saturation (89.68±3.66)% vs (98.46±4.84)%, rest pain (3.5±0.5) points vs (2.6±0.6) points, movement pain (3.6±0.5) points vs (2.5±0.5) points, and these differences were statistically significant(P<0.05). The levels of Interleukin-6 (IL-6) (102.30±17.00) pg·ml^-1 vs (85.68±21.20) pg·ml^-1 and tumor necrosis factor-alpha (TNF-α)(33.44±4.85) pg·ml^-1 vs (18.14±4.28) pg·ml^-1 in both groups exhibited an increase post-treatment, while the C-reactive protein (CRP) (75.51±10.54) mg·L^-1 vs (60.75±9.84) mg·L^-1 demonstrated a decrease compared to pre-treatment levels. Furthermore, the study group displayed significantly lower levels than the control group (P<0.05). After 10 days of treatment, the peak expiratory flow rate (3.31±0.52) L·s^-1 vs (5.69±0.74) L·s^-1, forced expiratory volume (1.46±0.29) L vs (2.06±0.38) L, and forced vital capacity (2.68±0.95) L vs (4.26±1.05) L of both groups exhibited significant improvements compared to pre-treatment levels. Moreover, the study group demonstrated significantly higher values than the control group (P<0.05). The incidence of postoperative complications in the study group was significantly lower compared to the control group (6 cases vs 14 cases, P<0.05). Additionally, the duration of bone callus formation(9.50±1.40) days and fracture healing (72.20±8.32) days in the study group was significantly shorter compared to the control group(11.35±2.15) days, (93.70±9.90) days (P<0.001). CONCLUSION Compared with traditional rib-preserving internal fixation, patients with MRF and flail chest treated with minimally invasive internal fixation with thoracoscopic nickel-titanium shape memory alloy surround bone plate have better therapeutic effect, because of less surgical trauma, less pain and inflammatory reaction, fewer postoperative pulmonary complications, faster and better recovery of lung function, and thus promote the recovery of patients.
Humans ; Male ; Female ; Middle Aged ; Adult ; Retrospective Studies ; Rib Fractures/surgery* ; Aged ; Minimally Invasive Surgical Procedures/methods* ; Flail Chest/surgery* ; Thoracoscopy/methods* ; Fracture Fixation, Internal/methods*

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.
Humans ; Bone Transplantation/methods* ; Membranes, Artificial ; Bone Regeneration ; Animals

Objective:To investigate optimal treatment strategy for pT3N0 laryngeal squamous cell carcinoma（SCC）. Methods:A retrospective study of 150 patients with pT3N0 laryngeal SCC treated in the First Affiliated Hospital of Chongqing Medical University was performed. The efficacies of partial laryngectomy and total laryngectomy, as well as surgery alone and postoperative radiotherapy were evaluated. The overall survival（OS）, disease specific survival（DSS） and disease-free survival（DFS） were analyzed with statistical package from SPSS. Results:Among the 108 patients with glottic laryngeal SCC, there were no significant differences in OS, DSS and DFS between the partial laryngectomy group and the total laryngectomy group（Log-rank=0.184, 0.010 and 0.051, P>0.05）. Similarly, there were no significant differences in OS, DSS and DFS between the surgery-alone group and postoperative radiotherapy group（Log-rank=0.214, 0.251 and 0.003, P>0.05）. Among the 38 patients with supraglottic laryngeal SCC, the OS in the total laryngectomy group was significantly higher than that in the partial laryngectomy group（Log-rank=7.338, P=0.007）. The DSS and DFS in the total laryngectomy group were higher than in the partial laryngectomy group, but the differences were not statistically significant（Log-rank=0.895 and 1.792; P>0.05）. The DFS in the postoperative radiotherapy group was significantly higher than in the surgery-alone group（Log-rank=7.172, P=0.007）, but there were no significant differences in OS and DSS between these two groups（Log-rank=0.010 and 0.876, P>0.05）. Conclusion:For pT3N0 glottic laryngeal cancer patients, the efficacy of partial laryngectomy is comparable to total laryngectomy, same as surgery alone and postoperative radiotherapy. For pT3N0 supraglottic laryngeal cancer patients, total laryngectomy could improve the overall survival, and postoperative radiotherapy could reduce the recurrence. Prospectively randomized study with large samples is still needed.
Humans ; Laryngeal Neoplasms/therapy* ; Laryngectomy/methods* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Male ; Female ; Middle Aged ; Disease-Free Survival ; Neoplasm Staging ; Aged ; Survival Rate ; Treatment Outcome

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

ObjectiveTo observe the clinical effectiveness and safety of She medicine （畲药） Diren Zishen Formula（地稔滋肾方） combined with acupuncture as adjunctive treatment for primary biliary cholangitis with liver and kidney yin deficiency syndrome. MethodsSeventy patients of primary biliary cholangitis with liver and kidney yin deficiency syndrome were randomly divided into a control group and a treatment group， with 35 patients in each group. The control group received oral ursodeoxycholic acid capsules （250 mg per dose， three times daily）. The treatment group received She medicine Diren Zishen Formula oral decoction （one dose daily， 200 ml per dose in the morning and evening， served warm） and acupuncture ［bilateral Sanyingjiao （SP6）， Taichong （LR3）， Ganshu （BL18）， Zusanli （ST36）， Fenglong （ST17）， once daily， 5 consecutive days per week］ in addition to the same treatment as the control group. The treatment duration was three months for both groups. Comparisons were made between the two groups before and after treatment for the following parameters， which were four traditional Chinese medicine （TCM） symptoms scores （skin itching， fatigue， jaundice， and flank pain）， TCM syndrome scores， liver function indicators including aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transferase （GGT） and total bilirubin （TBiL）， liver fibrosis markers including serum laminin （LN）， serum hyaluronic acid （HA）， serum type Ⅳ collagen （Ⅳ-C） and serum type Ⅲ procollagen （PC-Ⅲ）， and inflammatory factor indicators including serum interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α）. The effectiveness of TCM syndrome between the two groups was compared and safety evaluations were also conducted after treatment. ResultsA total of 32 cases were finally analyzed in the treatment group， while the control group had 31 cases. The total effective rate of TCM syndrome in the treatment group （87.50%， 28/32） was higher than that in the control group （67.74%， 20/31） （P＜0.05）. After treatment， the TCM symptom scores， syndrome scores， liver function， and liver fibrosis markers in both groups signi-ficantly decreased， while in the treatment group， the inflammatory factor indicators decreased after treatment， and more decreases were found than those in the control group （P＜0.05 or P＜0.01）. Both groups had good safety， and no adverse reactions were observed. ConclusionThe combination of She medicine Diren Zishen Formula and acupuncture as an adjunctive treatment for primary biliary cholangitis can significantly improve the clinical effectiveness， improve liver function， reduce inflammatory response， and alleviate liver fibrosis， with good safety.

Objective To investigate whether 3D-guided cone-shaped segmentectomy can achieve comparable long-term outcomes with lobectomy for deep early-stage lung cancer with diameter≤2 cm. Methods We retrospectively screened patients with deep early-stage non-small cell lung cancer (NSCLC) with diameter≤2 cm who underwent lobectomy or segmentectomy in the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018. All pulmonary segmentectomy was performed using 3D-guided cone-shaped segmentectomy with segment or subsegment as the resection unit. Univariate and multivariate regression analyses were performed by Cox proportional hazard regression model. The patients who underwent segmentectomy and lobectomy were matched 1∶1 by propensity-score matching analysis. The oncological outcomes of two groups were compared. Results Our cohort was divided into a segmentectomy group (n=222) and a lobectomy group (n=127). The age, total nodule size, solid component size and proportion of pure solid nodule in the lobectomy group were significantly higher than those in the segmentectomy group. The median follow-up time was 49 months. Surgical margins were negative in all patients. The local recurrence rate of segmentectomy was 0.45%. The disease-free survival (DFS) rate and overall survival (OS) rate of patients in the segmentectomy group were significantly better than those in the lobectomy group (5-year DFS rate: 98.64% vs. 89.77%, P<0.001; 5-year OS rate: 99.55% vs. 92.10%, P<0.001). Multivariate regression analysis showed that the differences between two groups were not significant [DFS rate: HR=0.52. 95%CI (0.11, 2.59), P=0.427; OS rate: HR=0.08. 95%CI (0.00, 3.24), P=0.179] after adjusting for other factors. After propensity score matching, 77 patients were preserved in both segmentectomy group and lobectomy group, with the mean nodule size of 1.44 cm and 1.49 cm and the mean consolidation tumor ratio (CTR) of 0.46 and 0.52, respectively. There was no statistical difference in DFS rate (P=0.640) or OS rate (P=0.310) between the two groups. Conclusion 3D-guided cone-shaped segmentectomy can be an acceptable treatment for low-grade malignant NSCLC deep in lung parenchyma with diameter≤2 cm, and its oncology effect is not inferior to lobectomy.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective:To investigate the characteristics of sleep disorders in patients with Alzheimer's disease and the intervention effect of integrated traditional Chinese and Western medicine.Methods:A total of 102 patients with Alzheimer's disease who had sleep disorders and received treatment at Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine were included in the observation group. A total of 102 patients who concurrently received physical examination in the same hospital were included in the control group. Clinical consultation was performed to analyze the types and characteristics of sleep disorders in patients with Alzheimer's disease. The included patients with Alzheimer's diseae were divided into group A and group B using the random number table method, with 51 patients per group. Group A received routine western medicine intervention, while group B received traditional Chinese medicine intervention and routine western medicine intervention. The types of sleep disorders were observed in patients with Alzheimer's disease and older adult patients who undergo physical examination. The changes in traditional Chinese medicine syndrome score and sleep quality were evaluated in groups A and B.Results:The incidence rates of screaming, difficulty in falling asleep, excessive daytime sleepiness, nocturnal restlessness, obstructive sleep apnea syndrome, and fragmented sleep in the observation group were 13.73% (14/102), 58.82% (60/102), 49.02% (50/102), 49.02% (50/102), 24.51% (25/102) and 98.04% (100/102), respectively, which were significantly higher than 1.96% (2/102), 23.53% (24/102), 17.65% (18/102), 4.90% (5/102), 5.88%(6/102) and 50.98% (52/102), respectively in the control group ( χ2 = 9.76, 26.22, 22.58, 50.40, 13.73, 59.46, all P < 0.05). After intervention, the scores of insomnia, dizziness and tinnitus, mental confusion, and forgetfulness in group B were 1.0 (0.00, 1.00) point, 0.00 (0.00, 1.00) point, 0.00 (0.00, 1.00) point, and 1.00 (1.00, 1.00) point, respectively, which were significantly lower than (1.00, 2.00) points, 1.00 (1.00, 2.00) points, 1.00 (0.00, 1.00) points, and 1.00 (1.00, 2.00) points in group A ( Z = -1.86, -2.13, -2.36, -2.00, all P < 0.05). After intervention, the Pittsburgh Sleep Quality Index score and the Modified Epworth Sleepiness Scale score in Group B were (7.56 ± 1.93) points and (13.02 ± 2.06) points, respectively, which were significantly lower than (10.87 ± 2.21) points and (16.44 ± 2.87) points in group A ( t = 8.05, 6.91, both P < 0.001). Conclusion:The main characteristics of sleep disorders in patients with Alzheimer's disease include screaming, difficulty in falling asleep, excessive daytime sleepiness, nocturnal restlessness, obstructive sleep apnea syndrome, and fragmented sleep. Combined traditional Chinese and western medicine can alleviate clinical symptoms and improve sleep quality in patients with Alzheimer's disease who have sleep disorders.

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.