Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

Objective To investigate the effect of ATP synthase inhibitory factor 1 (ATPIF1) on the antitumor activity of chimeric antigen receptor (CAR)-NK92 cells. Methods HER2-targeted CAR-NK92 cells with ATPIF1 overexpression or knockdown were constructed. CAR-positive expression rate was detected by flow cytometry. Cell proliferation capacity was measured using CCK-8 assay. Glycolytic capacity was analyzed by Seahorse metabolic analyzer. Mitochondrial membrane potential levels were detected using JC-1 probe. Target cell lysis rate was evaluated by firefly luciferase reporter assay. Expression levels of CD107a, natural-killer group 2 member D (NKG2D), granzyme B (GzmB), perforin, and interleukin 2 (IL-2) were detected via flow cytometry. Quantitative real-time PCR was used to measure the expression of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), tumor necrosis factor α (TNF-α), ATPIF1, and hexokinase 1 (HK1). The impact of glycolytic inhibition by 2-Deoxy-D-glucose (2-DG) on CAR-NK92 antitumor capacity was examined. Results Successfully generated HER2-targeting control CAR-NK92 cells, as well as ATPIF1-overexpressing and ATPIF1 knockdown CAR-NK92 cells. The ATPIF1-overexpressing CAR-NK92 cells showed significantly enhanced target cell lysis rate, elevated expression levels of NKG2D and CD107a, increased secretion capacities of Granzyme B (GzmB) and IL-2, and upregulated mRNA expression levels of IFIT1 and TNF-α, while ATPIF1-knockdown cells exhibited opposite effects. ATPIF1 overexpression induced metabolic reprogramming in CAR-NK92 cells, manifested by significantly decreased mitochondrial membrane potential (δpsim), markedly upregulated HK1 mRNA expression, and enhanced basal glycolysis and glycolytic capacity. After glycolysis inhibition with 2-DG (5 μmol/L), both ATPIF1-overexpressing and knockdown CAR-NK92 cells showed no significant differences in NKG2D and CD107a expression levels compared to control cells. Conclusion ATPIF1 regulates the antitumor activity of CAR-NK92 cells through modulating glycolytic metabolism. Overexpression of ATPIF1 can enhance the antitumor efficacy of CAR-NK92 cells.
Humans ; Glycolysis ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Granzymes/genetics* ; Hexokinase/metabolism* ; Cell Line, Tumor ; Interleukin-2/genetics* ; Cell Proliferation ; NK Cell Lectin-Like Receptor Subfamily K/genetics* ; Membrane Potential, Mitochondrial

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective:To construct decision indicator system for the allocation of life-support equipment on the basis of hospital-based health technology assessment(HB-HTA)theory,and explore its application value in the management for life-support equipment.Methods:The decision indicators of the allocation of life-support equipment were formulated from four dimensions that included equipment safety,effectiveness,suitability and economy on the basis of HB-HTA theory,so as to assess and manage the decision for allocation of equipment.A total of 149 using life-support equipment in clinical work in West China Hospital of Sichuan University from January 2022 to December 2023 were selected,and expert review mode was adopted to conduct decision for allocation of 138 equipment received management for allocation from January to December 2022,and the decision indicator system for the allocation of life-support equipment on the basis of HB-HTA theory was adopted to conduct decision management for the allocation of 143 equipment(included 132 equipment received expert review mode for management of allocation)that received management for allocation from January to December 2023.The predictive assessment value for target,the achievement ratio of HB-HTA performance,the result of examination of management level of 46 personnel from clinical department,15 personnel from department of equipment,and 11 personnel from other department in items of allocation of equipment were compared between two kinds of management modes for allocation.Results:The predictive assessment values for target of the allocation items of heart-support equipment,respiratory-support equipment,anesthesia-support equipment and other support equipment which adopted HB-HTA management mode for allocation were respectively 0.65±0.22,0.68±0.16,0.70±0.15 and 0.58±0.20,which were higher all than those of management mode of expert review for allocation,and the differences were statistically significant(t=3.362,3.585,f4.152,3.247,P<0.05).The achievement ratio of average performance of safety,effectiveness,suitability and economy of allocation items of HB-HTA management mode were respectively(97.29±1.65)%,(96.19±2.08)%,(95.82±2.29)%and(94.92±2.29)%,all of which were higher than those of expert review management mode for allocation,and the differences were statistically significant(t=2.297,2.377,2.753,2.951,P<0.05).The results of the personnel who worked in clinical department,equipment department and other department were respectively(93.24±3.12)scores,(95.35±3.22)scores and(95.78±1.82)scores in adopting HB-HTA management mode for allocation to conduct examination for the management level about allocation items of life-support equipment with allocation decision,all of which were higher than those of expert review management mode for allocation,and the differences of them were statistically significant(t=3.220,2.435,2.404,P<0.05).Conclusion:The application of HB-HTA theory in indicator system of allocation decision of life-support equipment can comprehensively analyze the safety,effectiveness,suitability and economy of equipment allocation,and enhance the scientific nature of declaring project for allocation of life-support equipment,and improve the achievement degree of the target of implementing the project of the allocation of life-support equipment,and raise the business level of the management team for the project of allocation of life-support equipment.

A retrospective analysis was conducted on the clinical data of 11 children with Protein-Losing Gastrointestinal Disease (PLG) presented with chronic diarrhea who were admitted to the Capital Institute of Pediatrics Affiliated to Capital Medical University from 2018 to 2025. The data included etiology, laboratory test results, endoscopic and imaging findings, treatment regimens, and prognosis. Among them, there were 6 males and 5 females, with a median age of 7.8 (1.6, 12.0) months, and 9 cases ≤1 year. The etiologies were intestinal lymphangiectasia ( n=5), infection-related enteritis ( n=2), Crohn′s disease ( n=1), eosinophilic gastroenteritis ( n=1), and unknown ( n=2). Clinical manifestations were characterized by chronic diarrhea ( n=11), hypoalbuminemia ( n=11), and immune dysfunction ( n=8). Gastrointestinal endoscopy was performed in 9 cases, and diagnosis was confirmed by endoscopic pathology in 8 cases. Among the 5 cases of intestinal lymphangiectasia, only 3 were confirmed by 99Tc-labeled human serum albumin ( 99Tc m-HSA) radionuclide imaging. Five cases of lymphangiectasia were treated with a high medium-chain triglyceride diet, 2 infectious cases were treated with antibacterial agens, and 3 immune diseases received immunomodulators. Ten cases were cured and discharged, while 1 child died of sepsis after intestinal malrotation surgery. It is suggested that childhood PLG mostly occurs in infancy, with intestinal lymphangiectasia as the main etiology. Endoscopic pathology is the main diagnostic method, and with the combination of nutritional and immunomodulatory therapy, the prognosis is good for most of PLG patients.

Objective: To investigate the feasibility of magnetic anastomosis for uretero-ileal anastomosis using experimental rabbit models. Methods: Six experimental rabbits were used as the models.The lower part of the left ureter was cut with scissors，the daughter magnet (DM) was placed in the middle of the ureter，and the distal end of the ureter was ligated.After that，the ileum wall was opened，the parent magnet (PM) was inserted through it，the positions of the PM and DM were adjusted so that their ends were attracted to each other，and then ileum wall incision was sutured.The operation time，intraoperative blood loss，postoperative complications and magnet discharge time were recorded.Two weeks after operation，left ureterography was performed to obtain the specimens of the uretero-ileal anastomosis，and to observe the patency of the anastomosis.The formation of the anastomosis was observed with naked eyes and light microscope. Results: Uretero-ileal magnetic anastomosis was performed successfully in 6 experimental rabbits.The operation time was 28-39（32.50±3.94） min，and the intraoperative blood loss was less than 5 mL.The rabbits recovered well after operation，and no complications were observed.All animals survived to the end point of observation.The disconnection time of magnet after operation was 9-13(10.83±1.72) days.The gross specimen showed that the anastomosis was patent.The histological observation showed that the mucosa of the anastomosis was continuous and smooth，and the anastomosis was well formed. Conclusion: Magnetic anastomosis is feasible for uretero-ileal anastomosis with simple operation and good anastomosis formation.After further experimental verification，this technique is expected to be used in clinical practice.

Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases. Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion (DRG) neurons but does not occur in their central axonal branches. By performing rat sciatic nerve or dorsal root axotomy, we determined the expression of the dysbindin domain containing 2 (DBNDD2) in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury, respectively, and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury. Furthermore, we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development. Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury. Bioinformatic analysis data showed that transcription factor estrogen receptor 1 (ESR1) interacts with DBNDD2, exhibits a similar expression trend as DBNDD2 after axon injury, and may targets DBDNN2. These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.
Animals ; Ganglia, Spinal/metabolism* ; Nerve Regeneration/genetics* ; Rats ; Axons/metabolism* ; Sciatic Nerve/injuries* ; Rats, Sprague-Dawley ; Male

Objective To analyze the tumor characteristics associated with achieving pathological complete response(pCR) and tumor prognosis in the patients undergoing laparoscopic rectal cancer surgery after neoadjuvant chemoradiotherapy(nCRT). Methods A retrospective review was conducted on clinical and pathological data of locally advanced rectal cancer(LARC) patients who underwent nCRT at Renji Hospital from January 2017 to January 2024. Factors influencing the achievement of pCR were analyzed, and the patients prognosis of pCR group and non-pCR group was compared. Results Univariate analysis, multivariate Logistic regression analysis, and receiver operating characteristic (ROC) curve analysis showed that tumor length less than 5 cm(cutoff value 5.24 cm) and baseline carcinoembryonic antigen(CEA) less than 5 μg/L(cutoff value 5.33 μg/L) were independent predictors of achieving pCR after nCRT in LARC patients. Prognostic survival analysis showed that the 3-year overall survival(OS) rate for pCR group and non-pCR group were 92.86% and 82.46%, respectively (P=0.193), and the 3-year disease-free survival (DFS) rate were 85.71% and 70.18%, respectively (P=0.141), with no statistically significant differences between the two groups. Conclusions Tumor length and baseline CEA level are independent predictors for achieving pCR after nCRT in LARC patients. Additionally, there were no statistically significant differences in 3-year OS and DFS between pCR group and non-pCR group.

Objective To evaluate the feasibility of establishing canine rectovaginal fistula ani-mal model using magnetic surgery techniques.Methods Ten female Beagle dogs were randomly di-vided into study group(n=5)and control group(n=5).The study group underwent rectovaginal fistula modeling using magnetic surgery technology,while the control group was subjected to sharp puncture of the rectovaginal septum followed by indwelling rubber tube placement to establish the model.Surgical procedure duration and postoperative adverse events were recorded in both groups.Two weeks later,the magnets and rubber tubes were removed.The formation of rectovaginal fistulas in the animals of two groups was observed,and the success rates of model construction of two groups were statistically analyzed.Results Both groups successfully completed the preparation of the recto-vaginal fistula models.The operative time in both groups was less than 2 minutes.No adverse events such as magnet detachment were observed in the study group during the postoperative period.In the control group,the rubber tube dislodged on day 6 post-surgery in one dog,leading to spontaneous healing of the fistula.Two weeks after surgery,the magnets and rubber tubes were removed.Naked-eye observation showed that the rectovaginal fistula formed well in the experimental dogs of the study group,while the rectovaginal fistula formed well in 4 experimental dogs in the control group.The success rate of model construction in the study group was 100％,and was 80％in the control group.Conclusion The construction of a canine rectovaginal fistula model by magnetosurgical techniques has the advantages of simple operation and high success rate.Magnetosurgical techniques may serve as an ideal animal model for constructing and studying the histopathological changes and treatment methods of rectovaginal fistulas.