BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective Based on quantile regression analysis, the influencing factors of relapse hospitalization expenses of adult leukemia patients were analyzed. Methods Analyze the composition and influencing factors of hospitalization expenses for leukemia recurrence patients in our hospital. Results From 2017 to 2022 , the per capita hospitalization cost for leukemia patients with recurrence showed an increasing trend year by year. The results of quantile regression model showed that age, payment method , length of stay, times of stay, operation and complications had an impact on the hospitalization expenses of patients at different quantiles, and the difference between different quantiles was statistically significant (P<0.05). Conclusions The quantile regression method can more clearly reflect the distribution of the variables of each factor , we can reduce the hospitalization expenses of patients by improving the coverage rate of medical insurance and controlling the length of stay.

With the rapid development of artificial intelligence technology,small molecule generation models have emerged as a significant research direction in the field of drug discovery.These models,including Generative Adversarial Networks(GANs),Variational Autoencoders(VAEs),and diffusion models,have proven to possess remarkable capabilities in optimizing drug properties and generating complex molecular structures.This article comprehensively analyzes the application of the aforementioned advanced technologies in the drug discovery process,demonstrating how they supplement and enhance traditional drug design methods.At the same time,it addresses the challenges facing current methods in terms of data quality,model complexity,computational cost,and generalization ability,with a prospect of future research directions.

Objective:To investigate the application value of porcine small intestinal sub-mucosa (SIS) acellular matrix mesh in laparoscopic inguinal hernia repair (LIHR).Methods:The prospective multicenter randomized controlled single-blind non-inferiority-type study was conducted. The clinical data of 216 patients who underwent LIHR in 4 medical centers, including Beijing Chaoyang Hospital of Capital Medical University et al, from April 2021 to August 2022 were selected. Patients were divided into two groups using a central randomization system. Patients in the experimental group were implanted domestic SIS mesh, and patients in the control group were implanted imported mesh of similar material origin. The baseline characteristics of enrolled patients were evaluated using the full analysis set, and the effectiveness indicators were evaluated using the protocol set. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the ttest. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers and/or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. If the lower limit of 95% confidence interval( CI) of the difference in effective rates between the experimental group and the control group was greater than the non-inferiority cut-off value of ?10%, the experimental group was considered non-inferior to the control group. Results:(1) Situations of the enrolled patients. A total of 216 patients were selected for eligibility, with 46 patients dropping out due to violation of the trial protocol, and the remaining 170 patients were included in the full analysis set. Nine patients were dislodged due to loss to follow-up, and 161 patients completed follow-up. One case in the experimental group was excluded due to violating the inclusion and exclusion criteria, while the remaining 160 patients were included in the protocol set (80 cases in the experimental group and 80 cases in the control group). There was no significant difference in the gender, age, body mass index (BMI), surgical method, Gilbert type of hernia, volume of intraoperative blood loss, operation time of patients between the experimental group and the control group ( P>0.05), confounding bias ensured comparability. (2) Study endpoints. ① Primary study endpoint. During the postoperative 6 month of follow-up, none of patient in the experimental group or the control group had hernia recurrence, with the recurrence rate as 0. Results of non-inferiority test showed that the difference of hernia recurrence between the two groups was 0 (95% CI as ?4.58% to 4.58%), with the lower limit of ?4.58% greater than the non-inferiority cut-off value of ?10%, which fulfilled the non-inferiority hypothesis. ② Secondary study endpoints. Cases with plasmapheresis during the follow-up were 18 in the experimental group and 29 in the control group, respectively, showing no significant difference between the two groups ( χ2=3.65, P>0.05). There were 4 cases with postoperative pain and 1 case with postoperative malaise in the experimental group, and there were 8 cases with postoperative pain and 0 case with postoperative malaise in the control group, showing no signifi-cant difference in the above indicators between the two groups ( P>0.05). None of patient in the experimental group or the control group had incision infection, enterocutaneous fistula, intestinal obstruction, intestinal canal injury, allergy and rejection, testicular inflammation and/or atrophy, or any other complication. Conclusion:Compared with imported mesh of similar material origin, domestic porcine SIS mesh is safe and effective in LIHR.

Objective:To investigate the characteristics and surgical management of mesh infection after tension-free repair of inguinal hernia.Methods:The clinical and follow-up data of 87 patients with mesh infection after tension-free repair of inguinal hernia at the Department of Hernia and Abdominal Wall Surgery,Beijing Chaoyang Hospital from 2018 to 2020 were retrospectively analyzed.Results:The most frequent type of repair was plug implantation, accounting for 57.5% of the procedures. The most common clinical presentation was a chronic sinus. 79.3% patients had a >3-month history of chronic infection. Staphylococcus aureus was the most common bacteria. All patients underwent open debridement. Fifty-one patients had a complete removal of the infected mesh, and 36 had partial removal. All patients were followed up for 18.7-54.2 months. There was no significant difference in the incidence of wound infection, seroma, hematoma, inguinal hernia recurrence, and chronic pain between those with complete removal and that partial removal (all P>0.05). Seventeen cases suffered recurrent sinus in the partial mesh removal group, and the incidence was significantly higher than that in the complete mesh removal group ( P<0.001). Conclusion:Infected mesh removal is an effective treatment for mesh infection after tension-free repair of inguinal hernia and should be removed as completely as possible.

Objective:To investigate the surgical treatment of mesh infection after lapa-roscopic inguinal hernia repair.Methods:The retrospective and descriptive study was conducted. The clinical data of 32 patients with mesh infection after laparoscopic inguinal hernia repair who were admitted to the Affiliated Beijing Chaoyang Hospital of Capital Medical University from January 2018 to December 2020 were collected. There were 30 males and 2 females, aged 59(range, 19-81)years. All patients underwent debridement. Observation indicators: (1) surgical and postopera-tive situations; (2) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between was conducted using Fisher exact probability. Results:(1) Surgical and postoperative situations. All 32 patients underwent debridement success-fully, with the operation time and volume of intraoperative blood loss as 110(range, 45-220)minutes and 24(range, 5-200)mL. Of the 32 patients, there were 6 cases undergoing open debridement, 26 cases undergoing laparoscopic exploration with 12 cases clarified the cause of infection, in which 4 cases had intestinal fistula by mesh infection breaking through the peritoneum and invading the intestinal tract and underwent laparoscopic intestinal fistula repair, 3 cases had significant amount of residual medical glue, 3 cases had mesh wrinkling and curling, 2 cases underwent peritoneum suturing with black silk thread. There were 18 cases undergoing complete removal of infected mesh and 14 cases undergoing partial mesh removal. There were 18 cases undergoing removal of infected mesh by laparoscopic posterior approach and 14 cases undergoing removal of infected mesh by open anterior approach. Twenty-nine of the 32 patients had bacterial culture and drug allergy testing, including 24 cases with positive cultures, while 5 cases with negative cultures. The duration of hospital stay of the 32 patients was 27.0(range, 9.0-85.0)days. (2) Follow-up. All 32 patients were followed up for 37.9(range, 18.7-52.5)months. There were 5 cases and 2 cases with postoperative incision infection in the 18 patients undergoing complete removal of infected mesh and 14 cases undergoing partial mesh removal, respectively, showing no significant difference between them ( P>0.05). There were 7 cases, 4 cases with seroma, recurrent sinus in the 18 patients undergoing complete removal of infected mesh and 5 cases, 6 cases in the 14 cases undergoing partial mesh removal, respectively, showing no significant difference between them ( P>0.05). None of patient in the two groups had hematoma, recurrent inguinal hernia or chronic pain. The 7 patients with incision infec-tion recovered effectively after symptomatic treatment. The 12 patients with seroma received no special treatment. The 10 patients with recurrent sinus underwent debridement, in which 9 cases did not experience any further abdominal wall infections and 1 case underwent the third debride-ment. Conclusion:The management of mesh infection following laparoscopic inguinal hernia repair necessitates the expertise of hernia specialists to complete remove the infected mesh or partial remove the infected mesh based on the specific clinical scenario.

Objective:To analyze the epidemiological characteristics, high risk factors and pathogenic factors of sepsis-related liver injury patients by collecting epidemiological data and the sequencing results.Methods:A total of 288 sepsis patients been admited to the Emergency Department of the First Affiliated Hospital of Air Force Military Medical University from January 1, 2018 to December 31,2019 were selected and divided into sepsis liver injury group ( n = 44) and sepsis without liver injury group ( n = 244) according to whether acute liver injury occurred or not. The differences ofthe general data, hematological parameters, severity of illness and other indicators at admission between the two groups were compared and analyzed. Logistic regression was used to analyze the risk factors of sepsis-related liver injury. Total of 8 septic patients with liver injury and 4 septic patients without liver injury were selected for RNA-sequencing. Ribonucleic acid (RNA) was extracted from peripheral blood mononuclear cell of patients, detected using RNA-seq, and differential genes were screened and analyzed. Results:Compared with the sepsis without liver injury group, patients in the liver injury group suffered less hypertension (11.4% vs. 30.3%) and relatively more chronic renal insufficiency (40.9% vs. 12.1%); more patients were admitted to the emergency department due to renal disease (43.2% vs. 24.6%), higher sequential organ failure score (SOFA) and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score (SOFA (points) 9.86 ± 3.59 vs. 5.41 ± 3.13, APACHE Ⅱ (points) (16.07 ± 4.41) vs. (14.46 ± 3.77), with prolonged hospital days (d): 8 (4.75, 13.75) vs. 6 (2, 9)]; in the liver injury group, the incidence of infection in respiratory and digestive systems (70.5% vs. 18.0%) andthe chance of infection with Staphylococcus aureus were higher (9.1% vs. 2.0%), and laboratory parameters (procalcitonin (PCT), lactate dehydrogenase (LDH), partial thromboplastin time (APTT), direct bilirubin (DBIL), aspartate aminotransferase (ALT), alanine aminotransferase (AST)) were significantly increased [PCT (μg/L) (23.90 ± 33.22) vs. (10.95 ± 20.18), LDH (U/L) 540.00 (370.50, 1177.00) vs. 168.00 (98.65, 875.18), APTT (s) (41.50 ± 3.13) vs. (36.23 ± 5.27), DBIL (μmol/L) 18.50 (10.10, 58.85) vs. 10.30 (7.60, 16.85), ALT (U/L) 67.00 (41.25, 164.00) vs. 29.00 (18.00, 51.25), AST (U/L), 101.00 (51.25, 174.75) vs. 35.00 (25.00, 65.50)], while platelet (PLT) and albumin (Alb) were significantly lower than those in the sepsis without liver injury group [PLT (× 10 9/L) 62.50 (38.50, 164.25) vs. 90.5 (66.25, 165.5), Alb (g/L) (30.17 ± 7.16) vs. (34.20 ± 6.50)] (all P < 0.05).Logistic regression analysis revealed that Staphylococcus aureus infection, thrombocytopenia, elevated procalcitonin, elevated lactate dehydrogenase, elevated total bilirubin, and elevated glutamyltransferase were associated with sepsis with acute liver injury (odds ratio, OR) with 95% confidence interval (95% CI) of 0.1167 (0.0380~0.7300), 0.9836 (1.0060~1.0290), 0.9986 (1.0000~1.0001), 0.9745 (1.0040~1.0170), 1.0020 (0.9940~1.0000), and 0.9931 (1.0000~1.0001), respectively. A total of 311 significantly differential expressed genes (DEGs) were selected, with 151 up-regulated genes and 160 down-regulated genes compared with the septic non-liver injury group. Further bioinformatics analysis reveled that the top 10 GO sequences are:①platelet α granules,② platelet α granule cavity,③wound healing,④cell migration,⑤multicellular organism process,⑥anatomical structure development,⑦cartilage ossification,⑧tissue development,⑨ keratinization,⑨Multicellular biological development. And KEGG pathway enrichment analysis revealed that human disease-related pathways were dominant, mainly including purine metabolism, AGE-RAGE signaling pathway, p53 signaling pathway, porphyrin and chlorophyll metabolism, nitrogen metabolism, mineral nutrient absorption, protein processing in the endoplasmic reticulum, and FoXo signaling pathway. Conclusions:Staphylococcus aureus infection, thrombocytopenia, elevated procalcitonin, elevated lactate dehydrogenase, elevated total bilirubin, and elevated glutamyltransferase were independent risk factors for sepsis liver injury. Coagulation dysfunction, apoptosis, and metabolic level changes may be important mechanisms of sepsis-associated liver injury, which are related to purine metabolism, porphyrin and chlorophyll metabolism and the expression of genes related to FoXo signaling pathway, Hippo signaling pathway, and p53 signaling pathway.

BACKGROUND: Acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) is a high-risk factor for morbidity and mortality in patients with AIDS. This study aimed to determine the prognostic factors associated with overall survival (OS) and to develop a prognostic nomogram incorporating computed tomography imaging features in patients with acquired immune deficiency syndrome-related non-Hodgkin lymphoma (AR-NHL). METHODS: A total of 121 AR-NHL patients between July 2012 and November 2019 were retrospectively reviewed. Clinical and radiological independent predictors of OS were confirmed using multivariable Cox analysis. A prognostic nomogram was constructed based on the above clinical and radiological factors and then provided optimum accuracy in predicting OS. The predictive accuracy of the nomogram was determined by Harrell C-statistic. Kaplan-Meier survival analysis was used to determine median OS. The prognostic value of adjuvant therapy was evaluated in different subgroups. RESULTS: In the multivariate Cox regression analysis, involvement of mediastinal or hilar lymph nodes, liver, necrosis in the lesions, the treatment with chemotherapy, and the CD4 ≤100 cells/μL were independent risk factors for poor OS (all P < 0.050). The predictive nomogram based on Cox regression has good discrimination (Harrell C-index = 0.716) and good calibration (Hosmer-Lemeshow test, P = 0.620) in high- and low-risk groups. Only patients in the high-risk group who received adjuvant chemotherapy had a significantly better survival outcome. CONCLUSION A survival-predicting nomogram was developed in this study, which was effective in assessing the survival outcomes of patients with AR-NHL. Notably, decision-making of chemotherapy regimens and more frequent follow-up should be considered in the high-risk group determined by this model.
Acquired Immunodeficiency Syndrome ; Humans ; Lymphoma, Non-Hodgkin ; Neoplasm Staging ; Nomograms ; Prognosis ; Retrospective Studies

Objective: To systematic evaluate the real experience of patients after falling during hospitalization and qualitative research on the cognition and demand for fall prevention will provide theoretical basis for patients, their families, medical staff and medical institutions to better carry out fall prevention. Methods: English databases such as PsycINFO, Medline, Embase, CINAHL, Cochrane, PubMed, and Chinese databases such as Chinese biomedical literature database, CNKI, Wanang database were retrieved by computer. Included qualitative studies on the emotional experience of fall of inpatients and their cognition and needs for fall prevention. The retrieval time limit was until November 1, 2018.The literature was evaluated using the quality evaluation criteria for qualitative research (2016) of the JBI evidence-based health care center, and the results were integrated using a pooled integration method. Results: A total of 8 studies were included, and 33 clear research results were extracted. Similar results were summarized and combined to form 7 new categories, which were integrated into 4 results. Results 1: psychological experience of hospitalized patients after falling down. Integration results 2: the causes of falls from the perspective of inpatients. Integration results 3: hospital fall prevention measures and evaluation from the perspective of inpatients. Integration result 4: inpatients expected to receive care from their families and help from medical staff. Conclusion Fall events seriously affect the mental health of patients; Patients′ cognition of falling is affected and changed by many factors. Fall prevention should shift from clinical focus to patient-centered and attach importance to the participation of family members.

The dual luciferase reporter gene system provides sensitive readout, while it relies on a constitutively-expressed control gene for readout normalization. However, most standard control reporter genes are not constitutively expressed under all conditions. Here, we report an effective method to construct a control reporter plasmid for the dual luciferase reporter gene system that would be suitable for hormone research in silkworm cell lines. First, we modified BmVgP78M, a stably-expressed constitutive promoter in silkworm cells by mutating its hormone-related element. Then, we constructed the pRL-VgP78M control reporter plasmid by replacing the SV40 promoter and chimeric intron sequences in pRL-SV40 with the BmVgP78M sequence. Finally, we confirmed that the pRL-VgP78M control reporter plasmid could be stably expressed in silkworm cell lines via cell transfection experiments, and it was unresponsive to the induction of ecdysone, juvenile hormone, or their transcription factors. We thus obtained a control reporter plasmid pRL-VgP78M that could be expressed stably and moderately in silkworm cells. It can be readily used as the control reporter plasmid of the dual luciferase reporter gene system for hormone research in silkworm cell lines. It will also provide a reference for construction of control reporter plasmids of dual luciferase reporter gene systems that are adaptable to cell lines isolated from other species.