BACKGROUND: This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy vs . chemotherapy, and neoadjuvant triplet vs . doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC). METHODS: We included LAGC patients from 47 hospitals in China's National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapy vs . chemotherapy alone, and neoadjuvant triplet vs . doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13% vs . 7.61%, χ2 = 4.039, P = 0.044), and the 2-year (77.60% vs . 61.02%, HR = 0.67, 95% con-fidence interval [CI] 0.43-0.98, P = 0.048) and 3-year (70.55% vs . 61.02%, HR = 0.58, 95% CI 0.32-0.93, P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons. CONCLUSIONS Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.
Humans ; Stomach Neoplasms/metabolism* ; Female ; Neoadjuvant Therapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use* ; Male ; Middle Aged ; Propensity Score ; Retrospective Studies ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease-Free Survival ; Cohort Studies

The production of healthy agricultural products has increased the demand for innovative and sustainable plant protection technologies, and the rapid advancement of nanotechnology has brought revolutionary breakthroughs to traditional agriculture. Nanocarrier-based drug delivery systems can not only significantly improve the utilization efficiency of pesticides, achieving enhanced efficacy and reduced application, but also decrease the pesticide residues and environmental pollution. Additionally, they have made breakthrough progress in the stability and persistence of RNA pesticides. This review summarized the research progress on nanopesticides and RNA pesticides, focusing on the mechanisms of nanocarriers in improving pesticide bioactivity and RNA interference (RNAi) efficiency. It also systematically summarized the types of nanomaterials and their applications in pest and disease management and provided an in-depth outlook for the future development of nanopesticides and RNA pesticides, which provided technical support for the high-quality development of agriculture in the future.
Pesticides/chemistry* ; Nanotechnology ; Nanostructures ; RNA ; Agriculture/methods* ; RNA Interference ; Drug Delivery Systems

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Objective:To investigate whether malignant tumors affect the laboratory outcomes of patients in their first controlled ovarian hyperstimulation (COH) cycle.Methods:This study was a retrospective case-control study that analyzed the clinical and laboratory data of patients who underwent fertility preservation before chemotherapy and radiotherapy due to malignant tumors, as well as patients with infertility caused by tubal factors who first underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2020 to May 2024. Patients who underwent fertility preservation were designated as the research group, while patients who underwent assisted reproduction due to tubal factors during the same period were designated as control group. After 1∶3 propensity score matching (PSM), 40 patients were included in the research group and 118 patients were included in control group. The ovarian response, oocyte retrieval outcomes, and embryonic development after fertilization in the first COH cycle were compared between the two groups. Results:After PSM, the research group and control group showed statistically significant differences in the gonadotropin (Gn) starting dosage [225.00 (162.50, 300.00) U vs. 193.75 (150.00, 225.00) U, P=0.002], duration of Gn used [10.00 (8.00, 11.00) d vs. 12.00 (10.00, 13.00) d, P<0.001], and average estradiol levels on human chorionic gonadotropin trigger day [2 487.00 (1 461.25, 4 090.25) pmol/L vs. 10 738.50 (8 400.00, 16 507.25) pmol/L, P<0.001]. However, no statistically significant difference was found in the total dosages of Gn used between the two groups ( P>0.05). There were no significant differences between the groups in terms of the number of oocytes retrieved, the number of metaphase Ⅱ oocytes, two pronuclei (2PN) rate, 2PN cleavage rate, available embryo rate, high-quality embryo rate, blastocyst formation rate, and available blastocyst formation rate (all P>0.05). Conclusion:Compared with infertility patients with tubal factors, there is no significant difference in the laboratory outcomes of malignant tumor patients undergoing COH for fertility preservation prior to chemotherapy and radiation.

Objective:To investigate the effects of male body mass index (BMI) on semen parameters and perinatal outcomes following artificial insemination by husband (AIH) treatment.Methods:A retrospective cohort study was conducted to analyze the clinical data of 5 053 patients underwent AIH treatment at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University, from January 2017 to February 2024. The study focused on factors such as male semen parameter abnormalities, male sexual dysfunction, female cervical factors, reproductive tract malformations, and unexplained infertility. Patients were classified into three groups based on male BMI: normal weight group (18.5-23.9 kg/m2, n=1 673), overweight group (24.0-27.9 kg/m2, n=2 078), and obese group (BMI≥28.0 kg/m2, n=1 302). The primary objective was to assess the differences in semen parameters and perinatal outcomes among the three groups. Multivariable logistic regression and linear regression analyses were applied to adjust for potential confounders that could influence semen parameters and perinatal outcomes. Results:Semen volume in the normal weight group and overweight group [4.00 (3.00, 5.50) mL, 4.00 (3.00, 5.50) mL] was higher than that in the obese group [4.00 (3.00, 5.00) mL], with a significant difference among the three groups ( P<0.001, a P<0.001). The total sperm count in the normal group and overweight group [207.60 (121.90, 341.75)×10 6, 211.80 (119.88, 334.83)×10 6] was higher than that in the obese group [188.40 (110.96, 323.41)×10 6], with a significant difference among the three groups ( P=0.007, a P<0.001). The total progressive sperm motility count in the normal group [88.18 (43.63, 163.80)×10 6] was higher than that in the obese group [75.30 (40.29, 147.86)×10 6], with a significant difference among the three groups ( P=0.001, a P<0.001). The percentage of forward motile sperm in the normal group [(45.37±17.16)%] was higher than that in the overweight group [(44.03±17.36)%] and the obese group [(43.80±17.21)%], with a significant difference compared among the three groups ( P=0.020, a P=0.016]. In terms of perinatal outcomes, after multivariate logistic regression analysis, only the overweight and obese groups had higher newborn birth weights [(3 389.53±472.65) g, (3 408.57±507.90) g] compared with the normal group [(3 271.32±532.02) g], with a significant difference among the three groups ( P=0.010, a P=0.009). Conclusion:Higher male BMI is associated with decreased semen quality and may increase newborn birth weight following AIH treatment.

OBJECTIVE To explore the possible mechanism of Qingchang Huashi Formula in the treatment of ulcerative colitis(UC).METHODS Fifty C57BL/6 male mice were randomly divided into a control(Ctrl)group,a model group,a low-dose Qingchang Huashi Formula group,a high-dose Qingchang Huashi Formula group,and a 5-aminosalicylic acid(5-ASA)group based on body weight.The UC model was established in mice by drinking 3%dextran sulfate sodium(DSS)for 6 d.On d7 and d8,DSS was withdrawn and ultrapure water was given daily.Ultrapure water or different drugs were administered orally throughout the experiment:Ctrl and model groups received 0.2 mL of ultrapure water,while the low-dose and high-dose Qingchang Huashi Formula groups re-ceived 6 and 12 g·kg-1,respectively,and the concentration of 5-ASA was 100 mg·kg-1.Body weight and fecal characteristics of the mice were recorded daily,and the experiment ended on d9.Serum was collected from mice for serum metabolomics and inflam-matory factor expression analysis.The colons of the mice were isolated and their lengths were measured,and the distal colon was ob-tained for pathological analysis.The livers and colons of the mice were isolated for subsequent total bile acid analysis.RESULTS Compared with the Ctrl group,the model group mice showed a significant decrease in body weight and colon length(P<0.000 1),a remarkable increase in disease activity index(P<0.000 1).The concentration of inflammatory factors IL-1β and TNF-α was signifi-cantly increased(P<0.000 1).High-dose and low-dose Qingchang Huashi Formula,as well as 5-ASA could significantly alleviate the loss of body weight,increased DAI,colon shortening,and disappearance of colon tissue morphology in mice.Through ELISA tes-ting,it was found the concentration of IL-1β and TNF-α was remarkably decreased after Qingchang Huashi Formula and 5-ASA treat-ment(P<0.01,P<0.000 1).Through LC-MS analysis of serum metabolites and KEGG enrichment analysis,we found that interven-tion with Qingchang Huashi Formula could significantly affect the primary bile acid synthesis,secondary bile acid synthesis and bile se-cretion.Using total bile acid reagent kit,we found that the total bile acid in the liver of colitis mice did not show significant changes when compared with the Ctrl group of mice,and the concentration of total bile acid in the serum was significantly reduced,the concen-tration of TBA in the colon was significantly increased(P<0.05).After intervention with the Qingchang Huashi Formula,the concen-tration of total bile acid in the serum of mice was significantly increased,while the concentration of total bile acid in the colon was re-duced(P<0.05).Compared with mice in Ctrl group,the levels of deoxycholic acid(DCA)and taurine deoxycholic acid(TDCA)in serum of colitis mice were significantly reduced(P<0.05).After intervention with Qingchang Huashi Formula,the levels of DCA,TD-CA and Ursodeoxycholic acid(UDCA)in serum of mice were restored(P<0.01).CONCLUSION Qingchang Huashi Formula can effectively relieve DSS-induced colitis in mice,reducing immune inflammatory response,reregulating the disorder of serum metabolism and enterohepatic circulation.

AIM:To study the clinical characteris-tics of hyperuricemia(HUA)in ulcerative colitis(UC)patients and the role of uric acid in UC through clinical and animal experiments.METH-ODS:The clinical research included UC patients hospitalized for the first time in the Department of Gastroenterology,Affiliated Hospital of Nanjing Uni-versity of Chinese Medicine from April 2019 to April 2023.The patients were divided into two groups based on the presence of HUA,and the clin-ical data and laboratory indicators were collected.In the animal experiment,24 SPF male C57BL/6J mice were randomly divided into ctrl group(Ctrl),model group(DSS),potassium oxonate group(PO),and uric acid group(UA).The body mass index,dis-ease activity index(DAI)score,pathology,inflam-mation,and intestinal barrier function indexes were compared among groups.RESULTS:The clini-cal research showed that the prevalence of HUA in UC patients was 9％(41/455).Patients with HUA had a significantly higher proportion of male and BMI levels,and more extensive colonic types(P＜0.05)than those without.In laboratory indicators,patients with HUA had significantly higher levels of C-reactive protein and triglyceride,and a substan-tially lower level of high-density lipoprotein choles-terol(P＜0.05)than those without.The animal ex-periment found that compared with the Ctrl group,the DSS group significantly decreased body weight,shortened colon length,and increased DAI score.Pathological results showed a large number of in-flammatory infiltrations and significant damage to the crypt structure.Moreover,the expression level of IL-6 in colon tissue was significantly increased,and the expression levels of MUC-2 and ZO-1 were significantly decreased(P＜0.05).Compared with the DSS group,both the PO group and UA group could aggravate the above symptoms,indicating that uric acid has a significant pro-inflammatory ef-fect on DSS-induced UC model mice.CONCLUSION:HUA is not uncommon in UC patients and such pa-tients have a wider range of lesions and more se-vere inflammation.The mechanism may be that high uric acid aggravates inflammation.

Objective·To evaluate the clearance and pharmacokinetics/pharmacodynamics(PK/PD)of antibiotics from the perspective of protein binding rates in critically ill patients undergoing intermittent hemodialysis(IHD),in order to explore the association between protein binding rate and dialysis clearance of antibiotics,and to provide theoretical basis for developing antibiotic dosing regimens during hemodialysis.Methods·Nineteen patients undergone low-flux hemodialysis and received antibiotic therapy at the Department of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,were enrolled and divided into the meropenem group(n=7),the vancomycin group(n=5)and the ceftriaxone group(n=7)according to the type of antibiotics.A liquid chromatography with tandem mass spectrometry(LC-MS/MS)method was established to detect meropenem,vancomycin,and ceftriaxone in human plasma/serum and dialysate.A two-compartment pharmacokinetic model was established using MATLAB.Instantaneous and total dialysis clearance rates were calculated,and PK/PD parameters were analyzed.Results·No significant differences were found in the clinical characteristics of subjects among the three groups.The dialysis clearance rates were as follows:meropenem group(5.14?5.97 L/h)>vancomycin group(2.87?3.77 L/h)>ceftriaxone group(1.21?1.90 L/h),with statistically significant differences(P<0.001).All three antibiotics showed good fit in the two-compartment pharmacokinetic model with a dialysate chamber(fval%<2),and the calculated PK/PD parameters were consistent with previous literature.For meropenem,the fraction of time that the free drug concentration remained above the minimal inhibitory concentration(%fT>MIC)values were 95.2%,60.8%and 32.4%at minimal inhibitory concentration(MIC)values of 2,8 and 16 μg/mL,respectively.For ceftriaxone(free concentration),the%fT>MIC values were all above 45.0%at MICs of 0.25,4 and 16 μg/mL.For vancomycin,only 14.0%of the trough concentrations reached the target range of 15?20 mg/L.Conclusion·The three antibiotics are well described by the two-compartment model.The plasma protein binding rate has a significant effect on the dialysis clearance of antibiotics in low-flux IHD,with higher protein binding associated with lower clearance.The regimens of meropenem(0.5 g/d)and ceftriaxone(2.0 g/d)are generally effective among patients undergoing low-flux IHD,while the vancomycin regimen with a loading dose of 1.0 g and a maintenance dose of 0.5 g/2 d carries a risk of treatment failure.

Senile trichiasis is primarily manifested by eyelid laxity, decreased horizontal elasticity and tension of the eyelids, leading to friction between the eyelashes and the cornea, which subsequently causes corneal damage and vision decline. Surgical intervention remains the most effective therapeutic approach for senile trichiasis. This article elaborates on the epidemiological characteristics, pathological mechanisms, and clinical manifestations of senile trichiasis and systematically reviews the surgical treatment method for upper and lower eyelid trichiasis, including traditional surgical techniques and emerging minimally invasive procedures combined with personalized therapies. Through a literature review, the effectiveness and recurrence rates of surgical treatment are summarized, emphasizing the importance of preoperative assessment and individualized treatment. Additionally, strategies and recommendations for preventing senile trichiasis are proposed.