Objective·To use single-cell RNA sequencing(scRNA-Seq)technology to interpret the cellular communication landscape of coronary atherosclerosis(CA),and to explore the dominant cell subsets and their key genes.Methods·The GSE131778 data set was downloaded and preprocessed,and quality controlling,dimension reduction clustering and annotation were carried out.Then cell communication analysis was conducted by using CellChat package to identify dominant cell subsets.The FindAllMarker function was used to screen differentially expressed genes(DEGs)between the dominant cell subpopulation and other cell subpopulations,and its protein-protein interaction(PPI)network was constructed.The DEGs ranked in the top five of the Degree algorithm were taken as key genes.Then,the key genes were matched and mined with the cell communication network analyzed by CellChat to obtain the ligand-receptor pairs(L-R)and the signal pathways mediated by the key genes,and the results were visualized.At the same time,the atherosclerosis mouse model was constructed and RT-PCR was used to detect the expression of key genes in carotid atherosclerosis lesions.Results·A total of 11 cell subsets were identified in CA lesions,including smooth muscle cells,endothelial cells,macrophages,monocytes,etc.Cell communication results showed that CellChat detected 70 significant L-R and 26 related signal pathways in 11 cell subsets.Smooth muscle cell was the dominant cell subgroup with the most significant interaction frequency and intensity with other cell subgroups in the active state of communication.The results of DEGs screening showed that there were 206 DEGs between smooth muscle cell subsets and other cell subsets,among which ITGB2,PTPRC,CCL2,DCN and IGF1 were identified as key genes.The results of cell communication mediated by key genes showed that CCL2 and ACKR1 formed L-R and participated in the communication network between smooth muscle cells and endothelial cells through mediating CCL signaling pathway.ITGB2 formed receptor complexes with ITGAM and ITGAX respectively,and then formed L-R with C3 to mediate the complement signal pathway,participating in the communication network among smooth muscle cells,macrophages and monocytes.The validation results of hub genes in animal experiments were consistent with the results of bioinformatics analysis.Conclusion·Smooth muscle cells are the dominant cells in the pathological process of CA,and have extensive communication networks with other cells.They can construct cellular communication networks with endothelial cells,macrophages and monocytes through CCL and complement signaling pathways mediated by CCL2-ACKR1,C3-(ITGAM+ITGB2)and C3-(ITGAX+ITGB2).

ObjectiveTo explore the mechanism of Buzhong Yiqitang in improving autoimmune thyroiditis （AIT） by regulating helper T cell 17（Th17） cells through microRNA-155 （miR-155）/Nedd4 family interaction protein 1 （Ndfip1）/phosphatase and tensin homology （Pten） axis. MethodThe 100 SPF grade 8 week-old NOD.H-2^h4 mice were fed with high iodine water （0.05% NaI） for 8 weeks， and AIT model was made. They were divided into model group， Buzhong Yiqitang low-，medium-，and high-dose groups （4.78，9.56，19.12 g·kg^-1·d^-1） and selenium yeast tablet group （3.033×10^-5 g·kg^-1） according to random number table method. There were 20 mice in each group and 20 mice in the control group. The control group and the model group were given the same amount of distilled water. After 8 weeks of continuous administration， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of miR-155-5p， Ndfip1， Pten， protein tyrosine kinase 1 （Jak1）， signaling and transcriptional activator 3 （Stat3） retinoic acid-associated orphan receptor γt （RORγt）， and interleukin-17 （IL-17） mRNA in mouse thyroid tissue. Western blot was used to detect the expression of Ndfip1， Pten， Jak1， Stat3， RORγt， and IL-17 proteins in mouse thyroid tissue， immunohistochemical method was used to detect the expression of Ndfip1 and Pten proteins in mouse thyroid tissue； flow cytometry was used to detect the proportion of Th17 cells in mouse spleen. ResultCompared with the control group， the proportion of Th17 cells was increased （P<0.01）. The expressions of miR-155-5p， Jak1， Stat3， RORγt and IL-17 were increased （P<0.01）， while the expressions of Ndfip1 and Pten were decreased （P<0.01）. Compared with model group， the proportion of Th17 cells was decreased （P<0.05，P<0.01）. The expressions of miR-155-5p， Jak1， Stat3， RORγt and IL-17 were decreased （P<0.05，P<0.01）， while the expressions of Ndfip1 and Pten were increased （P<0.05，P<0.01）. ConclusionThe application of Buzhong Yiqitang can improve the autoimmune disorder of AIT mice， the mechanism of which may be related to the regulation of Ndfip1/Pten axis by miR-155 and then the regulation of Th17 cell differentiation.

ObjectiveTo investigate the effects of Buzhong Yiqitang on the tumor necrosis factor receptor superfamily member 6 （Fas）/Fas related death domain protein （FADD）/Caspase-8 cell apoptotic signaling pathway in mice model with autoimmune thyroiditis （AIT）. MethodThere were 120 SPF grade NOD.H-2^h4 mice aged 8 weeks， 100 of which were fed with high iodine water （0.05% NaI）， and the AIT model was made after 8 weeks. According to random number table method， they were divided into model group， Buzhong Yiqitang low-dose， medium-dose and high-dose groups （4.78， 9.56， 19.12 g·kg^-1）， selenium yeast tablet group （3.033×10^-5 g·kg^-1）， with 20 mice in each group and 20 control group. The apoptosis of thyroid cells was detected by in situ end labeling （TUNEL） after 8 weeks of administration. The real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Fas， FADD， Caspase-8， and Caspase-3 in thyroid tissue. Western blot was used to detect the protein expression of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8， and cleaved Caspase-3 in thyroid tissue， and the immunohistochemical method was used to detect the protein expression of Fas and Caspase-3 in thyroid tissue. ResultCompared with control group， there were more positive expressions of apoptotic cells in model group under fluorescence microscope， and the expressions of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8 and cleaved Caspase-3 were significantly increased （P<0.05， P<0.01）. Compared with model group， the positive expression of thyroid apoptotic cells in each administration group was decreased under fluorescence microscope， and the expressions of Fas， FADD， Caspase-8， Caspase-3， cleaved Caspase-8， cleaved Caspase-3 were significantly decreased （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve thyroid cell apoptosis and inflammatory injury in AIT mice. The mechanism may be related to the inhibition of Fas/FADD/Caspase-8 signaling pathway.

Ureteral stenosis and bladder contracture after radiotherapy for cervical cancer are challenging issues in urology. Ileal ureteroplasty combined with ileal bladder augmentation is a potential method to improve hydronephrosis and voiding function of patients, however, the surgical procedure is complex, with high surgical risks and numerous intraoperative and postoperative complications, which have hindered the widespread application of this surgical technique. This article introduces our hospital's experience through a typical surgical case. During the surgery, ileal substitution for bilateral ureters was performed in combination with ileal " N-shaped" augmentation. Two weeks after the surgery, the single-J stent was removed, and the urinary catheter was removed three weeks after the surgery. The patient achieved voluntary urination control with smooth voiding. Follow-up examinations at 3 months and 18 months postoperatively showed no hydronephrosis in the bilateral ureters, normal renal function, and a significantly expanded bladder capacity.

Objective:To assess the efficacy and safety of computed tomography (CT)-guided percutaneous cryoablation in treating malignant liver tumors located explicitly at high-risk sites.Methods:Data were collected retrospectively from patients with malignant liver tumors undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. In all, 46 patients with malignant liver tumors at non-high-risk sites were matched 1∶1 according to the maximum tumor diameter. Technical success rate, complete ablation rate, and complications at 12 and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted. Univariate and multivariate logistic regression analyses were performed to identify risk factors.Results:Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. The complete ablation rate was 82.6% (38/46) and 71.7% (33/46) in the high-risk group and 84.8% (39/46) and 73.9% (34/46) in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups ( P>0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤5 mm and preoperative trans-arterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. Conclusion:CT-guided percutaneous cryoablation is a safe and effective approach for patients with malignant liver tumor at high-risk sites. Our results emphasize the importance of proper preoperative planning and intraoperative manipulation.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

【Objective】 To compare the clinical effects and screw placement accuracy for treating lumbar disc herniation between robot-assisted minimal invasive transforaminal lumbar interbody fusion (RA-MIS-TLIF) and minimal invasive transforaminal lumbar interbody fusion (MIS-TLIF). 【Methods】 We retrospectively recruited 69 patients with single segment lumbar disc herniation treated between January 2018 and August 2019 at Honghui Hospital of Xi’an Jiaotong University. There were cases of 33 RA-MIS-TLIF (RA group) and 36 MIS-TLIF (MIS-TLIF group). Subsequently, the patients’ baseline characteristics were collected, including age, gender, body mass index, complication with diabetes, duration of symptoms, operated segment, and follow-up time. We also collected perioperative parameters such as operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, screw placement accuracy, wound drainage, hospitalization duration, postoperative complicatins, and fusion rate. Lower back pain, lower extremity pain visual analogue score (VAS), and lumbar Japanese Orthopaedic Association Scores (JOA) were obtained preoperatively, postoperative 3 days/6 months/12 months, and the last follow-up. 【Results】 All the procedures were successfully completed and the follow-up time was 14.82±1.83 (RA group) and 15.11±1.62 (MIS-TLIF group) months, without significant difference (P>0.05). Compared with MIS-TLIF group, RA group had less intraoperative blood loss [(116.67±18.48) min vs. (128.06±22.53) min], fluoroscopy frequency [(12.42±2.28) vs. (15.67±2.46)], screw placement accuracy (93.18% vs. 84.03%), postoperative drainage [(73.03±23.52) mL vs. (88.33±28.54) mL], and shorter hospitalization stay [(6.45±1.52)d vs. (7.69±1.85) d] (all P<0.05). However, operation time did not significantly differ (P>0.05). The VAS of lower back pain and lower extremity pain, and lumbar JOA were significantly improved after the operation (P<0.001). At the same time point, there was no significant difference between the two groups (P>0.05). Meanwhile, fusion rate and incidence of complications did not significantly differ between the two groups (P>0.05). 【Conclusion】 Both robot-assisted MIS-TLIF and MIS-TLIF can achieve excellent clinical effects in treating single-segment lumbar disc herniation. However, the former can improve the accuracy of screw placement and reduce intraoperative blood loss, fluoroscopy frequency, postoperative drainage and hospitalization time, which indicates a promising application.

Ex vivo-expanded mesenchymal stem cells(MSCs)have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative,multipotential,and immunomodu-latory capacities.However,the exact characteristics of MSCs remain largely unknown.By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly,we revealed five distinct subpopulations.The developmental trajectory of these five MSC subpopulations was mapped,revealing a differentiation path from stem-like active proliferative cells(APCs)to multipotent progenitor cells,followed by branching into two paths:1)unipotent preadipocytes or 2)bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondro-cytes.The stem-like APCs,expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES,uniquely exhibited strong proliferation and stemness signatures.Remarkably,the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to sup-press activated CD3+T cell proliferation in vitro,supporting the role of this population in immunoregulation.In summary,our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation.Our findings advance the definition of MSCs by identifying the specific functions of their heteroge-neous cellular composition,allowing for more specific and effective MSC application through the purification of their functional subpopulations.