Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Colorectal cancer(CRC)is one of the most common malignant life-threatening tumors,with serious impacts on patient quality of life.Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)has recently become a hot topic in the field of cancer research,and has demonstrated a close relationship with CRC.SHP2,encoded by the PTPN11 gene,is a non-receptor tyrosine kinase commonly present in various tissues and cells of the human body.Existing research shows that SHP2 plays a crucial role in regulating CRC and colitis-associated colon cancer(CAC),and the emergence of SHP2 allosteric inhibitors has identified SHP2 as a potential new therapeutic target for patients with CRC.Here we review the structure of SHP2 and its roles in CRC and CAC.

Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.

Objective:To assess the current status of geriatrics department development in public general hospitals at or above the second grade in Shandong province.Methods:A cross-sectional survey was conducted from October 27 to November 3, 2023 using a web-based electronic questionnaire to investigate the current status of geriatrics department development in all public general hospitals at or above the second grade across 16 prefecture-level cities in Shandong province.The survey included participation from medical department staff and managers of geriatric medicine departments.Results:Shandong province has 355 public general hospitals at or above the second grade, of which 337 completed the questionnaire.Among these 337 hospitals, 92.28%(311/337)have established geriatric departments, 83.09%(280/337)have set up geriatric clinics, 69.14%(233/337)have independent geriatric wards, and 71.51%(241/337)have implemented comprehensive geriatric assessments(CGA).Regarding the configuration of geriatric departments, 60.24%(203/337)of hospitals met the requirement of having at least 20 ward beds, 34.42%(116/337)met the doctor-to-bed ratio requirement of at least 0.3, and 22.26%(75/337)met the nurse-to-bed ratio requirement of at least 0.6.Only 13 hospitals met all the requirements for geriatric wards, beds, doctors, and nurses, accounting for 3.86%(13/337)of the participating hospitals.Conclusions:The establishment of geriatrics departments in second-grade or higher public general hospitals in Shandong province has surpassed the national target in China ahead of schedule.Most hospitals have established geriatric clinics and wards and have implemented CGA.However, significant challenges remain, including a shortage of ward beds and a lack of medical staff.

Objective:To analyze risk factors for immune checkpoint inhibitor-related pneumonitis (CIP) in non-small cell lung cancer (NSCLC) patients based on clinical and radiological characteristics, and to develop and validate a nomogram model for predicting the risk of CIP.Methods:A retrospective case-controlled study was conducted. The clinical data of 159 patients diagnosed with NSCLC in Shanxi Province Cancer Hospital between January 2020 and December 2023 who received immune checkpoint inhibitor (ICI) therapy were retrospectively analyzed. Based on the development of CIP after immunotherapy, the patients were divided into the CIP group (30 cases) and the control group (129 cases). The clinical data of NSCLC patients, hematological indicators and the data of imaging characteristics before their first ICI treatment were collected. Quantitative assessments were performed on pretreatment chest CT images, including lung total tumor volume, number of involved lung segments, and pulmonary infection index. Logistic regression analysis was used to screen out the factors influencing the development of CIP. R 4.3.0 statistical software was used to construct a nomogram model for predicting CIP based on the statistically significant risk factors identified in the multivariate logistic regression analysis. The predictive performance of the model was evaluated by using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration curves and decision curve analysis (DCA) were employed to assess the model's consistency and clinical benefit.Results:There were statistically significant differences in the proportions of patients with a history of chest radiotherapy and those receiving different immunotherapy regimens between the control group and the CIP group (both P < 0.001). The difference in the lactate dehydrogenase (LDH) [ M ( IQR)] between the both groups was statistically significant [211.00 U/L (57.00 U/L) vs. 276.00 U/L (136.00 U/L), Z = -3.41, P < 0.001]; additionally, the difference in lung status score between the 2 groups was statistically significant ( P < 0.001). Multivariate logistic regression analysis revealed that a history of chest radiotherapy (with vs. without: OR = 4.200, 95% CI: 1.466-12.036), the combination of immunotherapy (monotherapy vs. the combined therapy: OR = 0.106, 95% CI: 0.022-0.509), LDH ≥ 255.5 U/L (< 255.5 U/L vs. ≥ 255.5 U/L: OR = 0.988, 95% CI: 0.981-0.995), and severe lung status score(mild vs. moderate vs. severe: OR = 0.187, 95% CI: 0.059-0.593) were independent risk factors for CIP development in NSCLC patients after immunotherapy (all P < 0.05). A nomogram model for predicting CIP occurrence was constructed based on chest radiotherapy history, immunotherapy regimen, LDH, and lung status score. ROC curve analysis showed the AUC was 0.878 (95% CI: 0.813-0.942). The calibration curve demonstrated the good consistency between the predicted risk probability of CIP and the observed outcomes; DCA indicated that the model had favorable clinical benefits. Conclusions:The constructed nomogram prediction model shows a good predictive performance.

Objective To investigate the effect of pneumoperitoneum pressure during robotic-assisted kidney transplantation (RAKT) on the function of the transplant kidney. Methods The data of 243 kidney transplant recipients were retrospectively analyzed and divided into open kidney transplantation (OKT) group (n=105) and RAKT group (n=138). The RAKT group was further divided into 13 mmHg group (n=67) and 7 mmHg group (n=71) based on pneumoperitoneum pressure. The donor information, recipient's preoperative general data, intraoperative data, and postoperative recovery of the three groups were compared. In the RAKT group, the renal artery, segmental artery, interlobar artery, and venous flow velocity of the transplant kidney were measured using laparoscopic ultrasound. Results There was a statistically significant difference in donor types among the groups (P<0.05), while other donor information and recipient's preoperative general data showed no statistically significant differences (all P>0.05). There were no statistically significant differences in serum creatinine and complications at 30 days and 1 year postoperatively among the groups (all P>0.05). The OKT group and 7 mmHg group had more intraoperative urine output than the 13 mmHg group. Both RAKT groups had less intraoperative blood loss and shorter hospital stays than the OKT group, and longer operation times than the OKT group (all P<0.05). There were no statistically significant differences in operation time, intraoperative blood loss, and hospital stay between the two RAKT groups (all P>0.05). The vascular flow velocity of the transplant kidney decreased at 13 mmHg compared to 7 mmHg pneumoperitoneum pressure, but the differences were not statistically significant (all P>0.05). Conclusions Controllable pneumoperitoneum pressure has a limited impact on the vascular flow velocity of the transplanted kidney. RAKT is a safe and effective surgical method under appropriate pneumoperitoneum pressure, and choosing a lower pneumoperitoneum pressure is more conducive to the early recovery of renal function postoperatively.

Objective To investigate the clinical efficacy of the Lower Limb Detumescence Formula(derived from Taohong Siwu Decoction)in treating lower limb swelling in patients with qi stagnation and blood stasis syndrome after total knee arthroplasty(TKA),and to analyze the changes in traditional Chinese medicine(TCM)syndrome types before and after surgery.Methods A total of 60 patients diagnosed with knee osteoarthritis and lower limb swelling with qi stagnation and blood stasis syndrome after TKA,hospitalized in the Department of Artificial Joints and Knee Surgery,The First Affiliated Hospital of Guangzhou University of Chinese Medicine between November 2024 and January 2025,were selected.Based on patients' preferences and postoperative medication,the patients were divided into three groups:the Chinese medicine Group(25 cases),the Lishang Group(15 cases),and the Aescuven Forte Group(20 cases).Changes in limb circumference on the affected side were used to describe knee volume changes,and were measured preoperatively and on postoperative days 1,3,and 30.Results(1)Regarding lower limb swelling,the calf and thigh circumferences of the affected side in all three groups showed a trend of early exacerbation(on postoperative days 1 and 3)followed by later relief(on postoperative day 30).Peak swelling occurred on postoperative day 3,with statistically significant differences compared to preoperative measurements(P＜0.05).Subsequently,swelling gradually alleviated,and the calf and thigh circumferences of the affected side progressively decreased,the circum ferences on postoperative day 30 differed from those on postoperative days 1 and 3(P＜0.05).However,there were no statistically significant differences in improving calf and thigh circumferences among the three groups(P＞0.05).(2)In terms of adverse reactions,the Lishang Group and the Aescuven Forte Group each reported two adverse events,including postoperative wound bleeding,subcutaneous ecchymosis,pulmonary infection,and constipation.The Chinese medicine group reported no gastrointestinal adverse events,and patient treatment compliance was better than that in the Lishang Group and the Aescuven Forte Group.(3)Regarding TCM syndrome differentiation,each patient received four assessments at different time points(preoperatively and on postoperative days 1,3,and 30),resulting in 240 valid data entries.Among these,qi stagnation and blood stasis syndrome was the most common(170 cases,70.83％),followed by liver and kidney deficiency syndrome(64 cases,26.67％),and qi and blood deficiency syndrome was the least common(6 cases,2.50％).(4)Comparison of the relationship between different groups and syndrome types revealed no significant association between group distribution and syndrome type(P＞0.05).Further generalized estimating equation analysis showed that grouping had no significant effect on TCM syndrome differentiation(P＞0.05).(5)Comparison of the relationship between different time points and syndrome types revealed that preoperative syndromes predominantly consisted of liver and kidney deficiency(96.67％),while on postoperative days 1 and 3,all cases were classified as qi stagnation and blood stasis syndrome(100.00％).On postoperative day 30,qi stagnation and blood stasis syndrome remained the most common(80.00％).There was a significant association between time points and syndrome distribution(P＜0.05).Further generalized estimating equation analysis indicated that time points significantly influenced TCM syndrome differentiation(P＜0.001).Conclusion The Lower Limb Detumescence Formula demonstrates efficacy comparable to Lishang Xiaozhong Oral Liquid and Aescuven Forte Tablets in improving lower limb swelling in patients with qi stagnation and blood stasis syndrome after TKA.By promoting blood circulation,resolving stasis,strengthening the spleen,and eliminating accumulation,this formula reduces the incidence of adverse reactions such as postoperative wound bleeding,subcutaneous ecchymosis,and constipation.It provides a new pharmacological option for treating lower limb swelling after TKA,and is particularly suitable for patients with qi stagnation and blood stasis syndrome accompanied by spleen deficiency.

AIM:To investigate the efficacy of Shenxiankang(SXK)in mitigating renal fibrosis in unilateral ureteral obstruction(UUO)mice,and elucidate its regulatory mechanism targeting the differentiation antagonizing non-protein coding RNA(DANCR)/TGF-β1/Smad3 signaling axis.METHODS:Mice were randomly assigned to:normal group(NC),model group(UUO),low,medium and high doses(1 500,3 000 and 4 500 mg·kg-1·d-1)of SXK group,and benazepril(10 mg·kg-1·d-1)group.Chronic kidney disease was modeled via unilateral ureteral ligation.Renal DAN-CR overexpression was induced using tail vein injection coupled with ultrasound microbubble technology.In vitro,human renal tubular epithelial cells(HK-2)were stimulated with TGF-β1;DANCR was either knocked down or overexpressed,followed by SXK intervention in both in vivo and in vitro models.Renal tissues were harvested for pathological assessment.DANCR expression and localization were analyzed using fluorescence in situ hybridization.Fibrosis deposition was evaluat-ed by immunohistochemistry(IHC).Western blot quantified the expression of fibrosis markers(α-SMA,FN)and key components of the TGF-β1/Smad3 signaling axis(p-Smad3,Smad3,TGF-β1).RESULTS:UUO mice exhibited signifi-cant renal tubular dilation.SXK intervention ameliorated renal lesions and reduced fibrosis.In UUO mice with DANCR overexpression,levels of renal fibrosis markers(α-SMA,FN)and TGF-β1/Smad3 signaling axis proteins(p-Smad3,Smad3,TGF-β1)were increased;these effects were reversed by SXK.In vitro,DANCR knockdown decreased the expres-sion of fibrotic proteins/mRNA and TGF-β1/Smad3 signaling axis components.SXK treatment effectively counteracted the fibrotic injury and TGF-β1/Smad3 signaling axis activation induced by DANCR overexpression.CONCLUSION:SXK ef-fectively mitigates renal fibrosis in UUO mice,potentially through regulation of the DANCR/TGF-β1/Smad3 signaling axis.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.