Objective To analyze the main causes and risk factors of unplanned reoperation after liver transplantation. Methods The clinical data of 242 liver transplant recipients in the First Affiliated Hospital of Anhui Medical University from January 2015 to December 2024 were retrospectively analyzed. According to whether unplanned reoperation was performed during the same hospitalization after surgery, the recipients were divided into the reoperation group (n=36) and the non-reoperation group (n=206). The preoperative, intraoperative and postoperative data of the two groups, as well as donor and graft-related data, were compared to analyze the risk factors of unplanned reoperation after liver transplantation and the survival status of the two groups. Results Among the 242 liver transplant recipients, 36 underwent unplanned reoperations, with a total of 54 procedures including various laparotomies, endoscopic and interventional surgeries, among which there were 20 laparotomies, 18 endoscopic surgeries and 16 interventional surgeries. The most common cause of unplanned reoperation was biliary complications (20 times), followed by vascular complications (17 times). Compared with the non-reoperation group, the reoperation group had longer graft cold ischemia time, higher postoperative fatality rate of recipients, longer length of stay in the intensive care unit and postoperative hospital stay, and higher total hospitalization costs (all P<0.05). The incidence of unplanned reoperation was higher in recipients who underwent split liver transplantation (P<0.05). Multivariate analysis showed that intraoperative blood loss ≥1 000 mL, positive culture of graft perfusate and split liver transplantation were independent risk factors for unplanned reoperation (all P<0.05). The postoperative 7-day, 1-month, 3-month and 6-month survival rates of recipients in the reoperation group and the non-reoperation group were 100% vs. 98.1%, 88.9% vs. 94.2%, 69.4% vs. 90.8% and 66.7% vs. 90.8%, respectively, and the postoperative survival rate of recipients in the reoperation group was lower than that in the non-reoperation group (P<0.05). Conclusions The main causes of unplanned reoperation after liver transplantation are biliary complications, vascular complications, abdominal incision infection and intra-abdominal hemorrhage. Intraoperative massive blood loss, positive culture of graft perfusate and split liver transplantation are the risk factors associated with unplanned reoperation after liver transplantation.

Objective To study the five-year survival status and influencing factors of elderly patients with lung cancer complicated with chronic obstructive pulmonary disease (COPD). Methods A cohort study was conducted to follow up 450 patients with lung cancer and chronic obstructive pulmonary disease who were hospitalized in our hospital from January 2018 to December 2023. The endpoint of the follow-up was the end of a five-year period or death. The Life Tables method was used to calculate survival rates and plot survival curves. The Cox proportional hazards model was used to analyze the influencing factors of five-year survival. Results The results indicated that the overall five-year survival rate of patients was 4.89%, and it decreased year by year. Cox regression analysis showed that age, gender, family functioning, and psychological status significantly influenced patient survival rate (all P<0.05). Stratified analysis found that the smoking status, family functioning, and psychological status of male patients all had an impact on survival rate (all P<0.05), while the psychological status of female patients had a more significant impact on survival (P=0.008). Conclusion This study provides a scientific basis for comprehensive intervention of elderly lung cancer patients with COPD. It is recommended that clinical attention should be paid to psychological and family factors to improve patient prognosis.

ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.

OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

ObjectiveTo analyze the epidemiological characteristics of 8 major respiratory pathogens in influenza-like illness (ILI) cases with acute respiratory infections at fever clinics in Huangpu District, Shanghai from 2015 to 2024, and to provide a scientific basis for the prevention and treatment of respiratory diseases. MethodsA retrospective study was conducted in Huangpu District. Individuals meeting the case definition of ILI from 2015 to 2024 was registered. Their nasopharyngeal swabs were collected for pathogen detection. A total of 8 respiratory viruses were tested, including Influenza A virus (Flu A), Influenza B virus (Flu B), adenovirus (ADV), enterovirus/human rhinovirus (EV/HRV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ResultsFrom 2015 to 2019, a total of 344 ILI cases were tested, of which 192 out of 344 cases (55.81%) were tested positive for single respiratory pathogen. From 2023 to 2024, 1 557 ILI cases were tested, with 572 out of 1 557 cases (36.74%) being positive for single pathogen. From 2023 to 2024, the positive rate of single pathogen in ILI cases was significantly lower than that in 2015‒2019 (χ²=42.66, P<0.001). Specifically, the positive rate of Flu A (χ²=74.43, P<0.001) decreased, while that of HPIV (χ²=8.66, P=0.003) increased, both with statistically significant differences. According to the seasonal pattern, the epidemic intensity of Flu A decreased in summer, while that of HPIV increased in summer and autumn. Demographic results showed statistically significant differences in the positive rates of EV/HRV between genders (χ²=22.38, P<0.001), with males exhibiting a higher positive rate than females. No statistically significant differences were identified in the positive rates of single pathogen among different age groups (χ²=4.42, P=0.110). Nevertheless, statistically significant differences were noted when comparing the positive rates of EV/HRV, Flu A, Flu B and HPIV across different age groups (P<0.05). EV/HRV was more commonly detected in the 15‒<25 age group (10.93%), while Flu A and HPIV had the highest positive rates in the ≥60 age group (21.24% and 4.77%). Flu B had the highest positive rate in the 25‒<60 age group (11.26%). 52.63% of cases with co-infections occurred during winter, with the primary pathogens involved being EV/HRV (9 cases) and HCoV (6 cases). The most prevalent combination of co-infection was Flu A with EV/HRV. ConclusionThe prevalence of respiratory pathogens among ILI cases from 2023 to 2024 exhibited notable fluctuations compared to that from 2015 to 2019. Therefore, influenza surveillance should be strengthened, and attention should also be paid to the prevalence of respiratory pathogens such as HPIV. These findings have profound implications for future research, surveillance, vaccine planning, and public health policy making.

Compared with traditional therapies for chronic liver disease （CLD）， Bifidobacterium has the characteristics of multi-target intervention， high biosafety， and good host compatibility and provides new strategies for intervention of CLD progression in terms of microecological regulation. Various studies have shown that Bifidobacterium regulates liver homeostasis and exerts a therapeutic effect on CLD by regulating intestinal flora， maintaining antioxidation， promoting energy consumption， alleviating inflammation， improving glycolipid metabolism， and exerting an antitumor effect. This article systematically reviews the studies on Bifidobacterium in the treatment of CLD in China and globally， explores their different mechanisms， and elaborates on the interaction between related signaling pathways （such as the nuclear factor erythroid 2-related factor 2 signaling pathway and the adenosine monophosphate-activated protein kinase signaling pathway） and the liver， in order to provide a basis for probiotic intervention in liver pathology， as well as new ideas for the comprehensive treatment of CLD.

OBJECTIVE To investigate the effects of galangin on rheumatoid arthritis （RA） in rats by regulating the Janus kinase 3 （JAK3）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Fifty male SD rats were taken， and an emulsion composed of bovine type Ⅱ collagen and Freund’s complete adjuvant was injected subcutaneously to establish an induced arthritis model. The rats that were successfully modeled were randomly divided into model group， low， medium and high dose groups of galangin （1， 5， 15 mg/kg）， and methotrexate group （positive control， 2 mg/kg）， with 10 rats in each group. Another 10 normal rats were taken as the normal group. Starting from the 15th day of modeling， each group of rats was gavaged with the corresponding drug solution or normal saline containing 0.5% Tween 80 once a day for 28 consecutive days. The arthritis index （AI） scores and paw volume of rats were compared before and after gavage administration. Twenty-four hours after the last administration， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10 were determined， the pathological changes in ankle joint synovial tissue were observed， and the protein expressions of UNC-51 like kinase 1 （ULK1）， Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， B cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， caspase-3， JAK3， phosphorylated JAK3 （p-JAK3）， STAT3 and phosphorylated STAT3 （p-STAT3） in the synovial tissue of the ankle joint were detected， as well as the fluorescence intensity of LC3-positive areas. RESULTS Compared with the model group， the pathological changes such as cellular proliferation of ankle joint synovial tissue and infiltration of inflammatory cells in rats of each administration group showed improvement. Moreover， their AI scores and paw pad volumes （on day 28 after gavage）， the levels of IL-6 and TNF-α， the protein expression of Bcl-2， and the phosphorylation levels of JAK3 and STAT3 were all significantly reduced （ P ＜0.05）. The levels of IL-4 and IL-10， the protein expressions of ULK1， Beclin-1， Bax， caspase-3 and LC3， as well as the fluorescence intensity of LC3-positive areas， were all significantly increased （ P ＜0.05）. Moreover， the effect of galangin was in a dose-dependent manner （ P ＜0.05）. CONCLUSIONS Galangin can induce sustained autophagy in synovial tissue cells of RA rats， promote cell apoptosis， inhibit synovial cell proliferation， and alleviate persistent inflammatory responses. The above anti-RA effects may be related to the inhibition of the JAK3/STAT3 pathway.

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.

ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.