Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Objective To compare the outcomes of transvaginal natural orifice transluminal endoscopic surgery(vNOTES)and laparoendoscopic single-site surgery(LESS)for total uterine excision in obese patients with benign uterine lesions,and to investigate the utility of vNOTES in this patient population.Methods A total of 100 obese patients(BMI>28.0 kg/m2)diagnosed with benign uterine lesions requiring total uterine and bilateral salpingectomy between January 2022 and January 2023 were included in this study.They were randomly assigned to two groups:the LESS group(n=51)and the vNOTES group(n=49).Patient demographics,surgical duration,intraoperative blood loss,changes in hemoglobin levels,pain scores,time to first flatus postoperatively,length of hospital stay,pelvic floor function,sexual quality of life,and postoperative complications were compared between the two groups.Results The two groups did not show any statistically significant differences in terms of blood loss,pre-and postoperative hemoglobin changes,pelvic floor function,sexual quality of life,or postoperative complications(P>0.05).However,the vNOTES group exhibited shorter surgical durations,time to first flatus postoperatively,and length of hospital stay compared to the LESS group(P<0.05).Additionally,the vNOTES group demonstrated lower intraoperative pain scores than the LESS group.(P<0.05).Conclusions In obese patients with benign uterine lesions,vNOTES total uterine excision surgery demonstrated shorter surgical durations and postoperative hospital stays,lower postoperative pain scores,and better adherence to the principles of en-hanced recovery after surgery(ERAS),indicating its potential for broader application.

Objective To explore the effect of repetitive transcranial direct current stimulation(tDCS)on anti-fatigue capacity,power output,and muscle activation during continuous vertical jumps of aver-age undergraduates.Methods Thirty healthy male college students were randomly assigned to an anodal tDCS(a-tDCS)group and a sham tDCS(sham-tDCS)group,receiving a total of 10 repeated anodal tDCS and sham tDCS for 5 consecutive days on the primary motor cortex respectively.Before and right after the intervention,as well as one month after the intervention,all students underwent the continuous vertical jump test.The two-factor repeated measure ANOVA(stimulation condition×time)was employed to evaluate alterations in fatigue index,total jump height,lower limb stiffness and mus-cle activation characteristics.Results The fatigue index of the a-tDCS group was significantly lower than the sham-tDCS group(P<0.05).After a-tDCS,the total jump height was significantly higher than before(P<0.05).In the sham-tDCS group,the touchdown time during continuous vertical jumps in-creased more significantly right and a month after the intervention(P<0.05 for both).Moreover,lower limb stiffness of the a-tDCS group at the last moment of the continuous vertical jumps was significant-ly higher than the sham-tDCS group(P<0.05).After a-tDCS,the activation of the rectus femoris mus-cle increased significantly in the eccentric phase of the end of the test(P<0.05).However,no signifi-cant differences were found in the mean power and post-test rating of perceived exertion after the stim-ulation.Conclusion Ten sessions of tDCS conducted over five consecutive days demonstrates an en-hancement in neuromuscular activation during high-intensity jumping exercise.This observed augmenta-tion contributes to attenuating the decline in exercise capacity associated with fatigue.

This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2 ) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E2 expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective:To investigate difficult-to-treat sites in patients with psoriasis receiving biological therapy.Methods:Clinical data were retrospectively collected from 73 adult patients with psoriasis in the database of Psoriasis Center, National Clinical Research Center for Skin and Immune Diseases from June 2020 to September 2021, who had received sufficient and standardized treatment with biological agents for ≥ 24 weeks, and were still treated with biological agents at the time of enrolment into this study with the psoriasis area and severity index (PASI) score being 1 - 5 at the time of enrolment into the database of Psoriasis Center. Distribution of psoriatic lesions resistant to biological therapy were analyzed, and differences in refractory sites were compared between different biologics. Chi-square test or Fisher′s exact test was used to analyze differences in the anatomical distribution of residual skin lesions after treatment with different biologics, McNemar test to compare the anatomical distribution of skin lesions before and after biological therapy, and Kruskal-Wallis H test to analyze the association between PASI scores for residual skin lesions and dermatology life quality index (DLQI) scores. Results:After ≥ 24 weeks of sufficient and standardized biological therapy in the 73 patients, refractory skin lesions mostly involved the lower limbs (46 cases, 63.01%) , followed by the scalp (36 cases, 49.32%) and upper limbs (27 cases, 36.99%) ; proportions of patients with residual skin lesions on the face and neck, trunk, upper limbs, lower limbs, hands and feet significantly decreased after biological therapy compared with those before treatment (paired χ2 = 5.14, 7.69, 9.90, 4.17 and 6.13, P = 0.016, 0.003, 0.001, 0.031 and 0.008, respectively) , while there was no significant difference in the proportions of patients with skin lesions on the scalp and genital areas before and after treatment (both P > 0.05) . No significant difference in the anatomical distribution of residual skin lesions was observed between the 13 patients receiving treatment with tumor necrosis factor inhibitors (adalimumab, infliximab, or tumor necrosis factor receptor-antibody fusion protein) and 59 receiving treatment with interleukin-17 (IL-17) inhibitors (secukinumab or ixekizumab) (all P > 0.05) . There was no significant difference in the anatomical distribution of residual skin lesions in the 13 patients before and after the treatment with tumor necrosis factor inhibitors (all P > 0.05) ; in the 59 patients treated with IL-17 inhibitors, the proportions of patients with residual skin lesions on the trunk, upper limbs, hands and feet significantly decreased after treatment (paired χ2 = 4.90, 9.09 and 7.11, P = 0.021, 0.001 and 0.004, respectively) , while there was no significant difference in the distribution of skin lesions on the scalp, face and neck, lower limbs and genital area before and after treatment (all P > 0.05) . Among the 73 patients, the PASI scores for lesions on the upper and lower limbs and the total PASI scores were all associated with the DLQI scores ( H = 7.52, 12.61, 6.75, respectively, all P < 0.05) , and were significantly higher in the patients with DLQI scores of > 10 points than in those with DLQI scores of ≤ 5 points (all P < 0.05) . Conclusions:Biological therapy-resistant psoriatic lesions were mostly located on the scalp, and refractory skin lesions mostly involved the lower limbs, scalp and upper limbs. No significant difference in the anatomical distribution of residual skin lesions was observed between patients treated with tumor necrosis factor inhibitors and IL-17 inhibitors, but IL-17 inhibitors may result in lesion clearance at more anatomical sites compared with tumor necrosis factor inhibitors.

Objective:To explore the risk factors of intensive care unit-acquired weakness (ICU-AW), and to establishment and verify its risk prediction model.Methods:A modeling group of 231 patients who met the inclusion criteria and were admitted to the intensive care unit (ICU) of the First Hospital of Jiaxing from July 2019 to June 2020 was collected by convenience sampling method. According to whether they developed ICU-AW, they were divided into ICU-AW group (55 cases) and non ICU-AW group (176 cases). The clinical data were collected concerning patients' individual information, disease-related factors, treatment-related factors and laboratory indicators, and the differences of the above indexes between two groups were compared. Logistic regression was used to analyze the ICU-AW risk factors and a risk prediction model was constructed. Calculate the area under ROC curve (AUC) to test the prediction effect of the model. At the same time, 60 patients who admitted to ICU from July to October 2020 and met the standards were collected to verify the model.Results:Compared with non ICU-AW group, there were more males in ICU-AW group [61.8% (34/55) vs. 44.3% (78/176), P < 0.05], with higher levels of systemic inflammatory response syndrome (SIRS), sepsis, immobilization and the use of neuromuscular blockers [SIRS: 30.9% (17/55) vs. 3.4% (6/176), sepsis: 12.7% (7/55) vs. 2.3% (4/176), immobilization: 72.7% (40/55) vs. 39.2% (69/176), the use of neuromuscular blockers: 50.9% (28/55) vs. 14.2% (25/176), all P < 0.05], and acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, blood lactic acid level and duration of mechanical ventilation, length of hospital stay were all increased [APACHEⅡ score: 18 (15, 24) vs. 12 (8, 17), blood lactic acid (mmol/L): 2 (1, 2) vs. 1 (1, 2), duration of mechanical ventilation (days): 7 (4, 12) vs. 2 (2, 5), length of hospital stay (days): 10 (6, 16) vs. 5 (3, 9), all P < 0.05]. SIRS, APACHEⅡ score, duration of mechanical ventilation and blood lactic acid were included to construct a risk prediction model [odds ratio ( OR) values were 4.835, 1.083, 1.210, 1.790, P values were 0.018, 0.013, 0.015, 0.013]. The model equation was P = exp [-5.207+(1.576×SIRS)+(0.079×APACHEⅡ)+(0.191×duration of mechanical ventilation)+(0.582×blood lactic acid)]. Internal verification: Calibration diagram showed the calibration curve above the ideal curve, AUC = 0.888, 95% confidence interval (95% CI) was 0.839-0.938; when the cut-off value was 0.166, the sensitivity was 89.1%, the specificity was 75.6%, and the maximum index was 0.649. External verification: Calibration diagram showed that the calibration curve was above the ideal curve, and the plotted AUC = 0.853, 95% CI was 0.753-0.953. When the cut-off value of the corresponding predictive risk value was 0.367, the sensitivity was 68.8%, the specificity was 86.4%, and the maximum approximate index was 0.552. Conclusion:The risk prediction model of ICU-AW constructed in this study has good consistency and prediction efficiency, which can provide reference for medical personnel to identify high-risk groups of ICU-AW patients in the early stage and provide targeted interventions in advance.

Objective? To explore the clinical effects of evidence-based psychological intervention on nursing care for middle-aged patients with ischemic stroke. Methods? Totally 120 patients aged 45-59 years who were hospitalized in the Department of Neurology, Cangzhou People's Hospital between February and July were selected, and stratified into intervention (n=60) and control (n=60) groups. Patients in the control group received conventional nursing care, while patients in the intervention group received psychological intervention based on conventional nursing care. Self-Depression Scale (SDS) was used to assess the status of patients in the two groups. Results? After 4 weeks, the SDS score of the intervention group was (52.37±4.38), whereas the SDS score of the control group was (58.81±3.44). The SDS score was lower in the intervention group than in the control group, and there was statistically significant difference between the two groups (P＜ 0.01). Conclusions? The evidence-based psychological intervention model helps to ameliorate the depression in middle-aged patients with ischemic stroke, which is worthy applying and promoting in clinical practice.