Colorectal cancer (CRC) is a common malignant tumor. The treatment of patients with advanced disease still faces severe challenges. Among patients with metastatic colorectal cancer (mCRC), most of those with microsatellite stable (MSS)/proficient mismatch repair (pMMR) tumors are highly insensitive to monotherapy with immune checkpoint inhibitors. With in-depth investigations into the mechanisms of the tumor immune microenvironment in MSS/pMMR CRC, the combination strategies of immunotherapy and targeted therapy have become a key direction to break through the treatment bottleneck in this population. These strategies include combinations of immunotherapy with antiangiogenic agents, epidermal growth factor receptor inhibitors, histone deacetylase inhibitors, and MAPK pathway inhibitors. Although the current relevant evidence is mainly derived from early-phase clinical trials, a number of studies demonstrated that immunotherapy combined with targeted therapy can improve the objective response rate and survival benefit in patients with MSS/pMMR mCRC and shows remarkable efficacy advantages in specific subgroups. This article systematically reviews the biological basis and clinical research progress of relevant combination therapeutic strategies, discusses potential beneficiary subgroups, and prospects future research directions. It aims to provide theoretical evidence and clinical references for optimizing the individualized treatment paradigm for this large patient population.

Objective To evaluate the prognostic value of radiation-induced lymphocytopenia in the survival of patients with primary hepatocellular carcinoma receiving radiation therapy. Methods The clinical data of 98 patients with unresectable primary hepatocellular carcinoma who received radiotherapy were retrospectively analyzed. The minimum absolute lymphocyte count (min ALC) was graded in accordance with CTCAE V4.0. The optimal threshold of min ALC for prognosis was calculated by using the receiver operating characteristic curve, and the correlation of min ALC with clinical characteristics and dosimetry parameters was analyzed. The Kaplan-Meier method was employed to analyze the survival of patients with different levels of min ALC. Univariate and multivariate Cox proportional regression models were applied to analyze prognostic factors. Results The baseline and min ALC of 98 patients during radiotherapy were 1.52×10⁹/L and 0.45×10⁹/L, respectively(P<0.001). The optimal cut-off value of min ALC for the prediction of the one-year survival rate was 0.38×10⁹/L. GTV, the mean dose of the liver and spleen, the V5 and V10 of the liver and spleen, and the V15 of the spleen were correlated with min ALC, and the V5 of the liver was an independent predictor of min ALC. The overall survival of patients with high min ALC was higher than that of patients with low min ALC. Independent prognostic factors were min ALC≤0.38×10⁹/L (HR=0.515, P=0.024), min ALC≥grade 3 (HR=0.576, P=0.032), tumor thrombus in the portal/vena cava, Child-Pugh grade A, increase of ≥2 points in the Child-Pugh score after radiotherapy, and received more than two other therapies. Conclusion Min ALC≤0.38×10⁹/L and min ALC≥grade 3 have independent prognostic value in patients with unresectable hepatocellular carcinoma receiving radiotherapy.

Objective:To investigate the effect of psychological intervention on postpartum depression.Methods:A total of 250 pregnant women who were hospitalized for delivery in the obstetrics ward of Jiaxing Maternity and Child Health Care Hospital from January 2021 to January 2022 were included in this randomized controlled study. The patients were randomly assigned to an observation group ( n = 125) and a control group ( n = 125) using a random number table. The observation group received psychological intervention, while the control group underwent routine ward rounds. Prior to and after intervention, the levels of depression [assessed by Edinburgh Postnatal Depression Scale (EPDS) score and Self-rating Depression scale (SDS) score] and anxiety [measured by Self-rating Anxiety Scale (SAS) score] were compared between the two groups. Results:Before intervention, the EPDS, SDS, and SAS scores in the observation group were (16.95 ± 4.20) points, (65.83 ± 7.52) points, and (61.12 ± 7.59) points, respectively. In the control group, these scores were (16.62 ± 4.03) points, (64.49 ± 7.98) points, and (60.88 ± 7.85) points, respectively. At 7 days post-discharge, the EPDS, SDS, and SAS scores in the observation group were (11.54 ± 2.39) points, (51.12 ± 4.62) points, and (49.71 ± 4.22) points, respectively. In the control group, these scores were (15.93 ± 3.87) points, (63.21 ± 6.95) points, and (59.65 ± 6.43) points, respectively. At 7 days post-discharge, the EPDS, SDS, and SAS scores in the observation group were significantly decreased compared with those before intervention ( t = 18.35, 27.09, 21.60, all P < 0.001). At 7 days post-discharge, the EPDS, SDS, and SAS scores in the observation group were significantly lower than those in the control group ( t = -10.79, -16.19, -14.44, all P < 0.001). There were no significant differences in EPDS, SDS, and SAS scores in the control group between before intervention and 7 days post-discharge ( t = 1.95, 1.91, 1.92, P = 0.051, 0.056, 0.055). Conclusion:Psychological intervention can effectively alleviate postpartum depression and anxiety in postpartum women and deserves clinical promotion.

Objective:To explore the safety and effectiveness of high power short duration (HPSD) ablation technique in elderly patients with atrial fibrillation.Methods:A total of 108 elderly patients with atrial fibrillation in the Department of Cardiology, the First Affiliated Hospital of Bengbu Medical University from January 2021 to June 2023 were randomly divided into the observation group (54 patients), who underwent HPSD catheter ablation and the control group (54 patients), who received conventional low power long duration (LPLD) catheter ablation. The radiation dose, ablation time, fluid infusion volume, pulmonary vein single lap isolation, and surgical complications were compared between the two groups. Follow up for 1 year after surgery to compare the success rates of the two groups.Results:The observation group had significantly lower radiation dose [(51.30±14.71)mGy vs. (77.77±13.97) mGy, P <0.01], ablation time [(57.98±16.95)min vs. (82.19±16.78)min, P <0.01]and saline infusion volume[(1284.31±212.07)mL vs.(1783.33±242.25)mL, P <0.01] compared with the control group. The pulmonary vein single lap isolation rates were similar in the two groups, and there were no serious surgical complications in the two groups. There were 17 cases of atrial fibrillation recurrence in the control group, higher than in the observation group (9 cases of recurrence), but there was no statistically significant difference between the two groups ( P =0.072). KM curve analysis showed that the maintenance time of sinus rhythm in the observation group was longer than that in the control group (Log Rank P =0.043). Conclusions:HPSD can significantly shorten the ablation time, reduce intraoperative saline infusion and radiation dose, and have a longer sinus rhythm time in elderly patients with atrial fibrillation. It is a safe and effective ablation method.

Objective:To evaluate the diagnostic accuracy of the convolutional neural network（CNN） in diagnosing nasopharyngeal carcinoma using endoscopic narrowband imaging. Methods:A total of 834 cases with nasopharyngeal lesions were collected from the People's Hospital of Guangxi Zhuang Autonomous Region between 2014 and 2016. We trained the DenseNet201 model to classify the endoscopic images, evaluated its performance using the test dataset, and compared the results with those of two independent endoscopic experts. Results:The area under the ROC curve of the CNN in diagnosing nasopharyngeal carcinoma was 0.98. The sensitivity and specificity of the CNN were 91.90% and 94.69%, respectively. The sensitivity of the two expert-based assessment was 92.08% and 91.06%, respectively, and the specificity was 95.58% and 92.79%, respectively. There was no significant difference between the diagnostic accuracy of CNN and the expert-based assessment （P=0.282, P=0.085）. Moreover, there was no significant difference in the accuracy in discriminating early-stage and late-stage nasopharyngeal carcinoma（P=0.382）. The CNN model could rapidly distinguish nasopharyngeal carcinoma from benign lesions, with an image recognition time of 0.1 s/piece. Conclusion:The CNN model can quickly distinguish nasopharyngeal carcinoma from benign nasopharyngeal lesions, which can aid endoscopists in diagnosing nasopharyngeal lesions and reduce the rate of nasopharyngeal biopsy.
Humans ; Nasopharyngeal Carcinoma ; Narrow Band Imaging ; China ; Neural Networks, Computer ; Nasopharyngeal Neoplasms/diagnostic imaging*

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Objective To evaluate the short-term efficacy and quality of life of primary hepatocellular carcinoma patients after radiotherapy and pregabalin treatment for neuropathic pain with bone metastasis. Methods 32 patients with primary hepatocellular carcinoma bone metastases were treated with radiotherapy combined with pregabalin treatment.Then, we prospectively studied the analgesic efficacy for neuropathic pain and quality of life, used the brief pain inventory and douleur neuropathique 4 questionnaire (DN4) to evaluate pain at baseline, one and two months after radiotherapy, assessed pain response using the international consensus endpoint definition of bone metastasis, and used European Organization for Research and Treatment of Cancer Research and Treatment Quality of Life Questionnaire (EORTC QLQ-C30) and bone metastasis module (QLQ-BM22) for quality of life assessment. Results One and two months after radiotherapy, the average DN4 score of neuropathic pain decreased, and the objective pain relief rates were 62.8% and 68.6%, respectively.The physical, emotional, social, and role functional scores of EORTC QLQ-C30 functional scale significantly increased in the first month after radiotherapy.Symptom scale of pain (P=0.015), insomnia (P=0.035), and loss of appetite (P=0.022) improved, and fatigue was aggravated (P < 0.05).Two months after radiotherapy, the mean overall health score and all functional scale scores significantly increased than those at baseline.The scores of all symptom scales decreased, except fatigue, constipation, and financial difficulties (P < 0.05).In addition, pain responders showed significant improvement in emotional function (P=0.025) and physical function (P=0.029) in the functional scale and in pain (P=0.014) and fatigue (P=0.035) in the symptom scale.The QLQ-BM22 score showed that the painful sites (P=0.021) and pain characteristics (P=0.04) of the responders significantly improved compared with those of nonresponders two months after radiotherapy. Conclusion Radiotherapy combined with pregabalin can relieve neuropathic pain caused by bone metastasis from primary hepatocellular carcinoma and greatly improve the quality of life, particularly in pain responders.

Objective:To explore the correlation of apparent diffusion coefficient (ADC) of magnetic resonance diffusion weighted imaging (DWI) examination before radiotherapy in patients with advanced cervical squamous cell carcinoma with clinicopathological characteristics and radiotherapy efficacy.Methods:The clinical data of 80 patients with advanced cervical cancer who were admitted to the Second Hospital of Nanjing from September 2019 to March 2022 were retrospectively analyzed. All patients underwent magnetic resonance imaging (MRI) DWI examination. The differences in ADC values among cervical squamous cell carcinoma patients with different clinicopathological characteristics were analyzed. The patients were divided into the effective group (complete remission+partial remission) and the ineffective group (stable disease+progressive disease) based on the radiotherapy effect, and the differences in ADC values between the two groups were compared. The logistic regression model was used to analyze the factors affecting the radiotherapy efficacy of patients with advanced cervical squamous cell carcinoma.Results:Among 80 patients with advanced cervical squamous cell carcinoma, 21 achieved complete remission, 31 achieved partial remission, 25 achieved stable disease, and 3 achieved progressive disease after radiotherapy; there were 52 cases in the effective group and 28 cases in the ineffective group. The ADC value of the effective group before radiotherapy was higher than that of the ineffective group [(0.99±0.14)×10 -3mm 2/s vs. (0.76±0.20)×10 -3mm 2/s], and the difference was statistically significant ( t = 6.01, P < 0.001); after radiotherapy, the ADC value of the effective group was also higher than that of the ineffective group [(1.43±0.25)×10 -3mm 2/s vs. (1.11±0.23)×10 -3mm 2/s), and the difference was statistically significant ( t = 5.61, P < 0.001); the ADC values of both the effective and ineffective groups increased after radiotherapy compared to before radiotherapy (both P < 0.05). The ADC values of patients with different International Federation of Obstetrics and Gynecology (FIGO) stage, degree of pathological differentiation, depth of lesion infiltration, Ki-67 expression, lymph node metastasis, and distant metastasis were statistically significant (all P < 0.05). The results of multivariate logistic regression analysis showed that ≥FIGO stage Ⅲ, low differentiation, lymph node metastasis, lymphatic vessel infiltration, distant metastasis, and low ADC value before radiotherapy were independent risk factors for efficacy of radiotherapy in patients with advanced cervical squamous cell carcinoma (all P < 0.05). Conclusions:The ADC value before radiotherapy is a factor that affects the radiotherapy effect of patients with advanced cervical squamous cell carcinoma. The lower the ADC value before radiotherapy is, the worse the radiotherapy effect of patients will be.

Bipolar disorder (BD) is a severe and disabling mental illness characterized by recurrent episodes of mania/hypomania or depression. Eating disorder (ED) refers to a group of syndromes mainly characterized by abnormal eating behaviors and excessive attention to food, weight, and body shape. Studies have found that BD and ED have high rates of comorbidity. ED is less common in males. We reported a male patient with comorbidity of BD and ED and introduced the diagnosis and therapy process to provide references for clinics.

Bipolar disorder (BD) is a severe and disabling mental illness characterized by recurrent episodes of mania/hypomania or depression. Eating disorder (ED) refers to a group of syndromes mainly characterized by abnormal eating behaviors and excessive attention to food, weight, and body shape. Studies have found that BD and ED have high rates of comorbidity. ED is less common in males. We reported a male patient with comorbidity of BD and ED and introduced the diagnosis and therapy process to provide references for clinics.