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.

OBJECTIVE To screen the potential active components of Polygonum orientale flower against myocardial ischemia- reperfusion injury （MIRI） in rats based on physiological and pathological states. METHODS SD rats were divided into normal control group， normal administration group， MIRI control group and MIRI administration group， with 5 rats in each group. After drug intervention or modeling and drug intervention， chromatographic separation plasma samples were collected， and chromatographic separation and mass spectrometry data collection were performed by using UPLC-Q-TOF/MS. The prototype components and metabolites were analyzed by comparing the reference substance maps， the maps of each plasma sample， and the relevant literature. At the same time， the common peaks in plasma samples of rats in normal administration group and MIRI administration group were identified. Combined with principal component analysis and orthogonal partial least square-discriminant analysis， the differential transitional components were screened out according to the value of variable importance in the projection （VIP）＞1， to speculate the potential active components of P. orientale flower in rats under physiological and pathological states. The SD rats were divided into control group， MIRI group， positive control group （Compound danshen tablets 0.2 g/kg， 3 times a day）， and potentially active compound groups （10 mg/kg， twice a day）， with 5 rats in each group. The rats in administration groups were given relevant medicine intragastrically， for 3 consecutive days. The activity of superoxide dismutase （SOD）， the leakages of lactate dehydrogenase （LDH）， creatine kinase isoenzyme-MB （CK-MB） and cardiac troponin Ⅰ （cTnⅠ） in plasma were detected after the last administration. RESULTS Twenty-six main chromatographic peaks were obtained from the total ion chromatogram of the extract of P. orientale flower， and 14 of them were determined， including gallic acid， catechin， protocatechuic acid and so on. There were fifteen （including 6 absorbed prototype components and 9 metabolites） and nineteen transitional components （including 6 absorbed prototype components and 13 metabolites） in the plasma sample of normal rats and MIRI rats. Eight transitional components were detected in both normal rats and MIRI rats， and the VIP values of kaempferol glucuronidation metabolites， quercetin carbonylation metabolites and N-p-paprazine to the corresponding peak were higher than 1. Compared with MIRI group， the activities of SOD were increased significantly in the plasma of MIRI rats in each potential active compound group （P＜0.01）， and the leakages of LDH， CK-MB， and cTnⅠ in the plasma of MIRI rats were reduced significantly （P＜0.01）. CONCLUSIONS The potential anti-MIRI active components in extract of P. orientale flower are N-p-paprazine， quercetin， kaempferol and kaempferol-3-O-β-D-glucoside.

Objective:To study the minimally invasive fixation with virtual self-designed screws between the iliac plates for acetabular posterior column fractures and compare the differences between genders.Methods:The CT data were collected from the 80 patients with normal pelvis who had undergone pelvic CT scan due to physical examination or trauma at Department of Orthopaedics, The Third Hospital of Xiamen from June 2021 to June 2022. There were 40 males and 40 females with an age of (45.0±12.4) years. The virtual screws between the minimally invasive iliac plates were designed with design software after 3D modeling. The insertion point, screw length, screw diameter, angle between the screw and the coronal plane of the pelvis, angle between the screw and the sagittal plane of the pelvis, angle ε between the screw and the anterior edge bone crest line of the greater sciatic notch, and bone channel volume were measured. Comparisons of the above data were made between genders. Results:The insertion point of the screw between the minimally invasive iliac plates was located between the anterior superior iliac spine and the iliac tubercle nodule, going toward the area between the ischial spine and the small ischial notch. The screw length was (139.64±8.46) mm, the screw diameter (8.95±1.16) mm, and the bone channel volume (51.91±10.77) cm 3. The screw length [144.34±7.58) mm], screw diameter [9.50±0.98) mm], angle between the screw and the sagittal plane of the pelvis (31.14°±2.74°), and bone channel volume [(57.82±8.82) cm 3] for males were significantly larger than those for females [(134.95±6.48) mm, (8.40±1.07) mm, 26.72°±2.74°, and (46.01±9.22) cm 3], while the angle between the screw and the sagittal plane of the pelvis [(35.74°±3.85°) mm] and angle ε between the screw and the anterior edge bone crest line of the greater sciatic notch (11.96°±4.57°) for males were significantly smaller than those for females (36.89°±2.96° and 14.17°±5.15°) (all P < 0.05). Conclusions:Fixation with screws between the iliac plates provides a new treatment for acetabular posterior column fractures, because the screws can be placed percutaneously in a minimally invasive manner or antegradely. The screw length, screw diameter, angle between the screw and the sagittal plane of the pelvis, and bone channel volume for males are significantly larger than those for females, while the angle between the screw and the sagittal plane of the pelvis and the angle between the screw and the anterior edge bone crest line of the greater sciatic notch for males are significantly smaller than those for females. Therefore, the angles between the iliac plate screw and the sagittal and coronal planes of the pelvis should be adjusted according to gender in screw placement.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Artificial intelligence has gradually become an important tool in the field of clinical nutrition. Artificial intelligence can not only simplify the current dietary assessment methods, but also develop nutritional assessment models with favorable accuracy through machine learning. Digital technologies and devices such as mobile applications and wearable devices have expanded the accessibility of dietary nutritional assessment. Mobile applications can be used for convenient and quick dietary nutritional assessment based on food images and videos, with real-time output of the types and amount of nutrients. Wearable devices can provide real-time feedback of individual dynamic nutrient intake and absorption by monitoring the fluctuation of the levels of biomarkers in body fluids. Nutritional assessment based on machine learning can improve the accuracy of malnutrition diagnosis, predict adverse events such as enteral nutrition intolerance, and guide nutritional intervention and prognosis prediction.

Objective To explore the value of serum homocysteine​（HCY） and cystatin C （Cys-C） levels for evaluating the presence and severity of cognitive impairment in elderly patients with both cerebral small vessel disease （CSVD） and obstructive sleep apnea-hypopnea syndrome （OSAHS）.Methods A retrospective study was performed on 150 elderly patients with both CSVD and OSAHS who were treated in our hospital from January to December 2020. The data about HCY and Cys-C levels were collected. According to the presence or absence of cognitive impairment， they were divided into observation group （with cognitive impairment， 41 cases） and control group （without cognitive impairment， 109 cases）. The serum HCY and Cys-C levels of the two groups were compared. The correlations between serum HCY and Cys-C levels and cognitive impairment in patients with both CSVD and OSAHS were analyzed. A binary Logistic regression analysis was performed to determine independent factors affecting cognitive impairment to establish a predictive logistic regression model. Receiver operating characteristic （ROC） curves were plotted to examine the predictive value of HCY， Cys-C， and their combination for cognitive impairment in patients with both CSVD and OSAHS. According to the severity of cognitive impairment， the patients in the observation group were further divided into mild cognitive impairment group （32 cases） and severe cognitive impairment group （9 cases） to compare HCY and Cys-C levels and analyze the value of HCY， Cys-C， and their combination in evaluating the staging of cognitive impairment by using ROC curves.Results The levels of HCY and Cys-C in the observation group were significantly higher than those in the control group （both P<0.05）. The total score of Montreal Cognitive Assessment was negatively correlated with serum HCY and Cys-C level （r=-0.756， -0.713， both P<0.001）. The logistic regression analysis showed that HCY and Cys-C levels were independent influencing factors for cognitive impairment （both P<0.05）. The area under the curve （AUC） of HCY plus Cys-C for prediction was 0.843（0.747-0.934）， which was higher than that of any single indicator （P < 0.05）， with the sensitivity and specificity being 89.32% and 79.25%， respectively. The levels of HCY and Cys-C were significantly lower in the patients with mild cognitive impairment than in those with severe cognitive impairment （both P < 0.05）. The AUC of HCY plus Cys-C in cognitive impairment staging was 0.925（0.849-0.976）， which was higher than that of any single index （P < 0.05）. The sensitivity and specificity were 95.67% and 89.67%， respectively.Conclusion Serum HCY and Cys-C levels are negatively correlated with the development and progression of cognitive impairment in elderly patients with both CSVD and OSAHS. The combined prediction with the two indicators can facilitate the evaluation of the risk and stage of cognitive impairment.
Homocysteine ; Cystatins

Objective:To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer.Methods:This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results:Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7–83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P=0.455); disease free survival was 90.0% and 83.3%, respectively ( P=0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P=0.625); and local recurrence rate both were 3.3% ( P=0.990), respectively. None of these differences was statistically significant. Conclusions:NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.

Objective:To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer.Methods:This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results:Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7–83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P=0.455); disease free survival was 90.0% and 83.3%, respectively ( P=0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P=0.625); and local recurrence rate both were 3.3% ( P=0.990), respectively. None of these differences was statistically significant. Conclusions:NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.