Objective To investigate the distribution characteristics of pathogens causing infections within 90 days after liver transplantation and the influencing factors of infection. Methods Clinical data of 176 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital Affiliated to Capital Medical University from September 2021 to August 2024 were retrospectively analyzed. Patients were divided into the infection group (n=124) and the non-infection group (n=52) based on whether they developed infection within 90 days after transplantation. The distribution characteristics of pathogens in infected patients were analyzed. Univariate and multivariate logistic regression analyses were used to explore the influencing factors of infection. Results Among the 176 liver transplant recipients, 124 cases developed 243 episodes of 518 bacterial, fungal, viral or mycoplasma infections within 90 days after transplantation, with an overall infection rate of 70.5% (124/176). The composition of pathogens was mainly Gram-negative bacteria (38.6%, 200/518), followed by Gram-positive bacteria (32.2%, 167/518) and viruses (15.4%, 80/518), and fungi accounted for 13.1% (68/518). Among Gram-negative bacteria, the main pathogen was Klebsiella pneumoniae (6.8%, 35/518), and among Gram-positive bacteria, the main pathogen was Enterococcus faecalis (8.5%, 44/518). Viruses included Epstein-Barr virus (3.7%, 19/518) and cytomegalovirus (3.7%, 19/518), and fungi were mainly Candida albicans (6.8%, 35/518). The most common infection site among the 243 episodes was pulmonary infection (42.0%, 102/243), followed by abdominal infection (22.6%, 55/243) and bloodstream infection (18.1%, 44/243). The infections mainly occurred within 2 weeks after transplantation (60.9%, 148/243). Multivariate logistic regression analysis indicated that preoperative infection within 2 weeks, a high preoperative model for end-stage liver disease (MELD) score, and preoperative sarcopenia were independent risk factors for infection within 90 days after liver transplantation (all odds ratio>1, P<0.05). After multivariate correction, the levels of CD4⁺T cells and CD8⁺T cells within 90 days after surgery were independently associated with the occurrence of infection. Low levels of CD4⁺T cells and CD8⁺T cells might be related to an increased risk of infection. Conclusions The infection rate after liver transplantation is high, and the pathogens are mainly Gram-negative bacteria. The lungs are the most common infection site. Preoperative MELD score, preoperative sarcopenia and preoperative infection within 2 weeks are independent risk factors for infection within 90 days after liver transplantation. Regular monitoring of immune indicators CD4⁺T cells and CD8⁺T cells levels after transplantation is helpful to reduce the occurrence of post-transplantation infection.

Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

ObjectiveTo investigate the mechanism through which miR‑21 improves chronic renal fibrosis in mice via targeted modulation of the phosphatase and tensin homolog （PTEN）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） pathway. MethodsThirty‑two chronic kidney disease model mice were randomly divided into four groups （n=8 each group）： model group， miR‑21 overexpression group， miR‑21 inhibition group， and miR‑21 inhibition + MK‑2206 group. Eight healthy mice were included as the control group. The miR‑21 overexpression， miR‑21 inhibition， and miR‑21 inhibition + MK‑2206 groups received tail‑vein injections of lentivirus （50 μL， 1×10⁸ TU per mouse） once weekly for three weeks. The control and model groups were injected with an equal volume of empty vector （LV‑NC）. The miR‑21 inhibition + MK‑2206 group additionally received gavage of the AKT/mTOR pathway inhibitor MK‑2206 （480 mg/kg） once weekly for three weeks. The expressions of miR‑21， 24 h urinary protein， serum creatinine （Scr）， blood urea nitrogen （BUN）， and renal tissue levels of collagen Ⅰ， collagen Ⅲ， α‑smooth muscle actin （α‑SMA）， and PTEN protein， as well as p‑AKT/AKT and p‑mTOR/mTOR ratios， were compared among groups. HE staining was used to observe pathological changes in renal tissue， and Masson staining was used to observe the degree of renal fibrosis. A dual‑luciferase assay was performed to verify the targeting relationship between miR‑21 and PTEN. ResultsCompared with the model group， miR‑21 expression in renal tissue increased in the miR‑21 overexpression group （P<0.05） and decreased in the miR‑21 inhibition group （P<0.05）. Compared with the model group， the miR‑21 overexpression group showed increased 24 h urinary protein， Scr， BUN， and renal tissue expression of collagen Ⅰ， collagen Ⅲ， and α‑SMA （all P<0.05）， while these indicators decreased in the miR‑21 inhibition group （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group exhibited lower 24‑h urinary protein， Scr， BUN， and renal tissue expression of Collagen Ⅰ， Collagen Ⅲ， and α‑SMA （all P<0.05）. Compared with the model group， the miR‑21 overexpression group showed decreased PTEN protein expression （P<0.05） and increased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， while the miR‑21 inhibition group showed increased PTEN expression （P<0.05） and decreased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group had lower p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， with no significant difference in PTEN protein expression. HE and Masson staining showed normal kidney structure and almost no fibrosis in the control group. The model group exhibited glomerular enlargement， capillary loop adhesion， and focal fibrosis. The miR-21 overexpression group showed severe destruction of glomerular structure， accompanied by extensive fibrosis and renal tubular atrophy. The pathological changes and degree of fibrosis were alleviated in the miR-21 inhibition group. The miR-21 inhibition + MK-2206 group showed only mild pathological changes and mild fibrosis， with the interstitium being largely normal. Compared with PTEN-WT + NC mimics 1， the relative luciferase activity in the PTEN-WT + miR-21 mimics group decreased （P<0.001）. There was no statistically significant difference in relative luciferase activity between PTEN-WT + NC mimics group and PTEN-MUT + miR-21 mimics group. ConclusionmiR‑21 may improve renal function indicators and alleviate renal fibrosis in chronic kidney disease mice via targeted modulation of PTEN and subsequently inhibiting the AKT/mTOR pathway.

OBJECTIVES: To qualitatively assess the diagnostic performance of dynamic contrast enhancement (DCE), diffusion-weighted imaging (DWI), and T2-weighted imaging (T2WI), alone or in combination, in the evaluation of breast cancer. METHODS: We retrospectively reviewed the records of 394 consecutive patients with pathologically confirmed breast lesions who had undergone 3-T magnetic resonance imaging (MRI). The morphological characteristics of breast lesions were evaluated using DCE, DWI, and T2WI based on BI-RADS lexicon descriptors by trained radiologists. Patients were categorized into mass and non-mass groups based on MRI characteristics of the lesions, and the differences between benign and malignant lesions in each group were compared. Clinical prediction models for breast cancer diagnosis were constructed using logistic regression analysis. Diagnostic efficacies were compared using the area under the receiver operating characteristic curve (AUC) and DeLong test. RESULTS: For mass-like lesions, all the morphological parameters significantly differentiated benign and malignant lesions on consensus DCE, DWI, and T2WI (P<0.05). The combined method (DCE+DWI+T2WI) had a higher AUC (0.865) than any of the individual modality (DCE: 0.786; DWI: 0.793; T2WI: 0.809) (P<0.05). For non-mass-like lesions, DWI signal intensity was a significant predictor of malignancy (P=0.036), but the model using DWI alone had a low AUC (0.669). CONCLUSIONS Morphological assessment using the combination of DCE, DWI, and T2WI provides better diagnostic value in differentiating benign and malignant breast mass-like lesions than assessment with only one of the modalities.
Humans ; Female ; Breast Neoplasms/pathology* ; Retrospective Studies ; Middle Aged ; Adult ; Diffusion Magnetic Resonance Imaging/methods* ; Aged ; Magnetic Resonance Imaging/methods* ; Young Adult ; Aged, 80 and over

AIM:To study the efficacy and molecu-lar mechanism of PX-478 in enhancing radiotherapy effect of lung cancer.METHODS:H460,A549 cells were divided into blank group,radiation group and radiation combined PX-478 group.In addition to the blank group,the radiation group and the PX-478 group were given 2Gy X-ray irradiation to estab-lish the radiation model,and the radiation com-bined with the PX-478 group was given 20 μmol/L PX-478 intervention after modeling,and cultured for 24 h.Inverted microscope was used to observe cell growth and cell number,CCK-8 method was used to detect cell viability,cloning was used to ob-serve cell proliferation,flow cytometry was used to detect cell apoptosis,and Western blot was used to detect HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA pro-tein expression.RESULTS:Compared with blank group,the number of H460,A549 cells in radiation group decreased,cell viability and proliferation abil-ity decreased,cell apoptosis rate increased,HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA protein expression increased(P＜0.01).Compared with the radiation group,the number of H460,A549 cells in the radia-tion combined PX-478 group was significantly de-creased,the cell viability and proliferation ability were significantly weakened,the apoptosis rate was significantly increased,and the protein expres-sions of HIF-1α,GLUT1,HK2,PFK1,PKM2 and LDHA were significantly decreased(P＜0.01).CONCLU-SION:PX-478 can regulate the HIF-1α-mediated gly-colysis in A549,H460 cells after radiation,regulate the energy metabolism,increase the apoptosis of tumor cells,and improve the effect of radiotherapy.

Objective:To analyze the characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD), and to explore the comorbidity of pneumoconiosis and COPD and its influencing factors.Methods:From October to December 2022, 255 pneumoconiosis patients admitted to an occupational disease prevention and control hospital from January 2018 to December 2021 were selected as the study subjects. According to whether the pneumoconiosis patients were complicated with COPD or not, they were divided into pneumoconiosis and COPD comorbidity group and pneumoconiosis group. The general condition and dust exposure of the two groups of patients were analyzed, and the relationship between different types and different periods of pneumoconiosis and COPD comorbidity was analyzed by multivariate logistic regression.Results:A total of 255 subjects were collected, including 64 patients with comorbidity of pneumoconiosis and COPD, and the comorbidity rate was 25.1%. There were 186 males (72.9%) and 69 females (27.1%), ranging in age from 35 to 90 (63.79±11.79) years, and working age from 1 to 45 (20.31±10.57) years. The comorbidity of pneumoconiosis and COPD increased with the increase of working age (χ 2trend=8.19, P=0.004), and the comorbidity rate for COPD with working age of more than 30 years was 37.7% (23/61). The comorbidity rate of pneumoconiosis and COPD also increased with the increase of the stage of pneumoconiosis (χ 2trend=13.14, P<0.001), and the comorbidity rate of pneumoconiosis and COPD in the stage Ⅲ was as high as 44.0% (11/25). The cumulative dust exposure was negatively correlated with forced expiratory volume in one second/forced vital capacity (FEV 1/FVC), and the linear regression equation y=-0.04 x+78.4. Multivariate logistic regression analysis showed that the length of services ≥30 years ( OR=3.30, 95% CI: 1.15-9.52) and stageⅡ ( OR=3.05, 95% CI: 1.03-9.04) were the risk factors for comorbidity between pneumoconiosis and COPD ( P<0.05) . Conclusion:The comorbidity rate of pneumoconiosis and COPD is high. Working age, pneumoconiosis stage and cumulative dust exposure are the main influencing factors of pneumoconiosis and COPD comorbidity, so more attention should be paid to the comorbidity of pneumoconiosis and COPD.

Objective:To investigate the role of vitamin E succinate (VES) in inducing autophagy of human gastric cancer cells by activating calcium redistribution through inositol 1, 4, 5-trisphosphate receptors (IP 3R) pathway. Methods:Human gastric cancer lines MKN28 (moderately differentiated) and MKN45 (poorly differentiated) cells were cultured in vitro in March 2022. Gastric cancer cells were treated with VES at different doses for 24 h, and cell viability was measured by CCK-8 method to determine VES dose for subsequent study. The experiment was set up with solvent control group (0.1% ethanol), VES dose groups, 100 nmol/L rapamycin (RAPA) as autophagy positive control group (RAPA group), 15 μg/ml tunicamycin (TM) was used as the endoplasmic reticulum stress (ERS) positive control group (TM group), 10 μmol/ml 2-aminoethyl diphenylborinate (2-APB group) was used to inhibit IP 3R (2-APB group) and VES+2-APB group. The occurrence of autophagosomes in gastric cancer cells was observed by transmission electron microscopy, and microtubule associated protein 1 light chain 3 (LC3), Beclin1, IP 3R, glucose-regulated protein 75 (Grp75), voltage-dependent anion channel 1 (VDAC1) protein expression was detected by western blotting. Fluo-4 AM was used to label intracellular calcium ions, Rhod-2 AM was used to label mitochondrial calcium ions, and the fluorescence intensity of calcium ions was observed by fluorescence microscope. One-way analysis of variance was used to compare the means among multiple groups, and LSD- t method was used for pairwise comparison. Results:CCK-8 results showed that compared with solvent control group, the proliferation rates of MKN28 cells in 10-100 μg/ml VES group and MKN45 cells in 20-100 μg/ml VES group were significantly decreased ( P<0.05). Subsequent VES dosages were determined according to the growth curve, MKN28 was 5, 10, 20, 40 μg/ml, and MKN45 was 10, 20, 40, 80 μg/ml. The results of transmission electron microscopy and fluorescence showed that autophagosomes were formed in MKN28 cells in 5 and 20 μg/ml VES groups and MKN45 cells in 10 and 40 μg/ml VES groups, and the fluorescence intensity of calcium ions in cytoplasm and mitochondria was significantly higher than that in solvent control group ( P<0.05). Compared with solvent control group, LC3, Beclin1, IP 3R, Grp75 and VDAC1 protein expressions of MKN28 cells in 20 and 40 μg/ml VES groups and MKN45 cells in 40 and 80 μg/ml VES groups were significantly increased ( P<0.05). After inhibiting IP 3R with 2-APB, the expression levels of IP 3R, Grp75 and VDAC1 in two kinds of gastric cancer cells in VES+2-APB group were significantly decreased compared with VES group ( P<0.05). The fluorescence results showed that the fluorescence intensity of cytoplasmic and mitochondrial calcium ions in VES+2-APB groups was significantly lower than that in VES group ( P<0.05). Compared with VES group, LC3 and Beclin1 protein expressions in two kinds of gastric cancer cells in VES+2-APB groups were significantly decreased ( P<0.05) . Conclusion:VES may activate intracellular calcium redistribution through IP 3R-Grp75-VDAC1 calcium channel and induce autophagy in gastric cancer cells.

Renal injury is one of the common ad-verse reactions in the clinical application of chemo-therapy drugs,which is the main reason why the chemotherapy can not be carried out in the whole cycle.The pathological mechanism of chemothera-py-induced renal injury is very complicated,mainly involving oxidative stress,inflammatory response,apoptosis,mitochondrial dysfunction,and regula-tion of transporters,causing pathological damage to renal tubules or glomeruli.At present,there is no specific pharmacological intervention for the treatment of chemotherapy-induced renal injury.As a treasure of traditional Chinese medicine,tradi-tional Chinese medicine has the advantages of overall regulation,multi-targeting,small adverse re-actions and no obvious drug dependence in the prevention and treatment of chemotherapy-in-duced renal injury.In recent years,there have been more and more studies on the intervention of che-motherapy-induced renal injury by multi-compo-nent and multi-directional intervention of active components,extracts and compounds of tradition-al Chinese medicine,and some progress has been made.A large number of studies have shown that the potential mechanisms of traditional Chinese medicine in preventing and treating renal injury in-duced by chemotherapy include inhibiting oxida-tive stress,reducing inflammatory response and in-hibiting apoptosis.Although there are many stud-ies on the mechanism of action of traditional Chi-nese medicine in the treatment of chemotherapy-induced renal injury,there is still a lack of systemat-ic review.Based on this,this paper summarizes the mechanism of renal injury induced by chemothera-py and the intervention of traditional Chinese medi-cine,so as to provide theoretical support for its clinical treatment and new drug innovation.

Objective To investigate the diagnostic and therapeutic value of single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis therapy in the treatment of acute uncomplicated appendicitis.Methods A retrospective analysis was conducted on the clinical data of 39 patients with acute uncomplicated appendicitis who underwent single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis treatment at the Endoscopy center of the hospital from September 2022 to September 2024.Observe the endoscopic manifestations,the rate of maternal and child basket stone removal,the rate of appendiceal stent implantation,the technical success rate,the clinical success rate,the operation time,the hospital stay,the incidence of complications,the visual analogue scale(VAS)score 6 hours after the operation,and the inflammatory indicators 24 hours after the operation.Results In 28 cases(71.8%),congestion and edema could be seen at the opening of the appendix under colonoscopy.In 10 cases(25.6%),pus could be seen flowing out of the opening of the appendix under colonoscopy.In 32 cases(82.1%),a large amount of pus could be seen in the lumen of the appendix under subscopy.In 20 cases(51.3%),appendiceal fecalith could be seen in the lumen of the appendix under subscopy.The technical success rate of single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis treatment was 100.0%(39/39).The operation time was(21.08±7.49)min;Hospital stay:(3.97±2.08)days;Eight cases(20.5%)of patients underwent endoscopic maternal basket stone removal.Appendiceal stent implantation was performed in 14 cases(35.9%)of patients.The clinical success rate is 97.4%(38/39).One patient's clinical symptoms and inflammatory indicators did not improve after the operation,and was transferred to the surgery department for appendectomy.The VAS score of 38 patients was less than 3 points 6 hours after the operation,and the abdominal pain symptoms were significantly relieved.The white blood cell count and the percentage of neutrophils 24 hours after the operation decreased significantly compared with those before the operation,and the differences were statistically significant(P<0.05).None of the 39 patients had complications.The postoperative follow-up was(5.94±4.03)months,and recurrence occurred in 3 cases(7.7%).Conclusion single-use mother-baby choledocoscope-assisted endoscopic retrograde appendicitis therapy is safe and effective in the diagnosis and treatment of acute uncomplicated appendicitis,which is worthy of further promotion and popularization in clinical practice.

Purpose To investigate the clinicopathologic,molecular genetic features of metastatic adenoid cystic carcinoma(ACC)of the liver.Methods The histological morphological characteristics,immunophenotype and prog-nosis of metastatic ACC in 4 cases of liver biopsy specimens collected were retrospectively analyzed,and the genetic characteristics were analyzed by fluorescence in situ hybridization(FISH).Results There were 3 male patients and 1 female patients,ranging in age from 41 to 66 years,with an average age of 52.5 years.Pathologically,the tumor cells showed a variety of tubular,cribriform or solid structures.The tumor cells had a bland morphology,composed of two layers of cells:the luminal cells with eosinophilic cytoplasm and round nuclei,and the peripheral cell with deeply stained,triangular or irregular nuclei.Immunohistochemistry showed that CK7,CK19 and CD117 were positive in lu-minal cells.p63,Calponin,SMA and CK5/6 were positive in peripheral cells.TTF-1,Napsin A,CD10,CD56 and CRP were negative,and Ki67 proliferation index was 8％-20％.4 patients had a history of adenoid cystic carcinoma of lung or submandibular gland.FISH results showed that MYB gene rearrangement in case 3 and MYB gene amplifica-tion in case 2.All 4 patients were diagnosed with liver metastatic ACC.After 27 to 65 months of follow-up,all the 4 patients had multiple systemic metastases such as bone and lymph nodes,of which 1 patient died of disease 36 months after surgery,and 3 patients survived with tumor.Conclusion The histological morphology of metastatic ACC in the liver is similar to that of benign and malignant tumors and metastatic tumors of the primary bile duct in the liver,espe-cially when it presents as small tubular form.The characteristic morphology of the two layers of epithelia should be carefully observed during diagnosis,and the patient history should be asked.Combined with the histochemical results and molecular detection,it can distinguish from primary and metastatic tumors such as hepatic bile duct adenoma,in-trahepatic small bile duct type cholangiocarcinoma,hepatic metastatic epithelial-myoepithelial carcinoma and metastatic adenocarcinoma.