ObjectiveTo investigate the effects of Trpc6 knockout on chronic lipopolysaccharide （LPS）-induced myocardial inflammation and fibrosis in mice and its potential mechanisms. MethodsMale C57BL/6 wild-type （WT） mice and Trpc6 knockout （Trpc6^-/-） mice of the same background were randomly divided into four groups： WT control， WT+LPS （200 μg/kg）， Trpc6^-/- control， and Trpc6^-/-+LPS （200 μg/kg）. Group with LPS received intraperitoneal LPS injections for 21 consecutive days to induce chronic myocardial inflammatory injury. Cardiac ultrasound assessed changes in left ventricular ejection fraction （EF）， left ventricular shortening fraction （FS）， and cardiac output （CO）. Hematoxylin and eosin （HE） staining and periodic acid-Schiff （PAS） staining were used to examine morphological alterations in myocardial tissue. Masson’s trichrome staining was used to assess myocardial fiber alterations； Western blot analysis was used to measure myocardial tissue expression of transient receptor potential calcium channel 6 （TRPC6）， NOD-like receptor family pyrin domain-containing 3 inflammasome （NLRP3），absent in melanoma 2 inflammasome （AIM2）， Caspase-1， interleukin （IL）-6， and IL-1β in mouse myocardial tissue. ResultsCompared with the WT control group， the WT+LPS group exhibited decreased cardiac EF （P<0.01）， FS （P<0.01）， and CO （P<0.05）， along with significantly increased myocardial tissue damage， glycoprotein deposition， and fibrosis （P<0.01）. Further analysis revealed that compared with the WT control group， the WT+LPS group exhibited markedly increased myocardial tissue expression of TRPC6， NLRP3， AIM2， Caspase-1， IL-6， and IL-1β （P<0.01）. Compared with the WT+LPS group， mice in the Trpc6^-/- +LPS group exhibited elevated EF （P<0.01） and FS （P<0.05）， along with reduced myocardial tissue injury， glycoprotein deposition， and fibrosis （P<0.05）. ConclusionChronic LPS treatment can activate NLRP3/AIM2 inflammasomes through the up-regulation of TRPC6 expression， and then lead to chronic myocardial inflammatory injury and fibrosis， while Trpc6 knockdown can reduce myocardial inflammatory injury and fibrosis， and the mechanism is related to inhibiting the activation of NLRP3/AIM2 inflammasomes.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To explore the role of diffusion tensor imaging (DTI) in monitoring prognosis after contralateral C7 nerve transfer in patients with central paralysis.Methods:The clinical data of a 56-year-old male patient with right limb motor impairment after cerebral infarction, admitted to the Department of Neurosurgery at Brain Hospital of Hunan Province in October 2023, were retrospectively analyzed. The patient had experienced right limb motor dysfunction for over 2 years following a cerebral infarction and was treated with contralateral C7 nerve transfer. Follow-ups were conducted at 2 and 6 months postoperatively. Motor function was assessed using the Fugl-Meyer Assessment (FMA) and Activities of Daily Living (ADL) scale, while changes in fractional anisotropy (FA) in the lesion area and corticospinal tract were monitored via DTI.Results:Postoperative follow-up of patient showed: (1) Significant improvement in motor function: ADL scores increased from 65 preoperatively to 75 (2 months postop) and 80 (6 months postop); FMA scores increased from 46 to 58 (2 months postop) and 61 (6 months postop). Muscle tension in the affected upper limb decreased markedly, and range of motion in the right shoulder joint improved. (2) Imaging improvements: DTI revealed an increase in FA values from 0.157 to 0.174 in the lesion area and from 0.52 to 0.53 in the corticospinal tract, indicating partial restoration of neural tract integrity.Conclusions:Contralateral C7 nerve transfer can effectively improve motor function in stroke patients. DTI technology provides an objective imaging basis for clinically assessing functional recovery by quantitatively evaluating changes in neural tract integrity, demonstrating significant value in guiding rehabilitation.

Objective:To investigate the risk factors for delirium after free flap reconstruction surgery in elderly patients with head and neck cancer.Methods:This study retrospectively collected clinical data from 309 elderly patients with head and neck cancer who underwent radical resection and free flap reconstruction surgery in the Department of Operation & Anesthesiology, College & Hospital of Stomatology, Guangxi Medical University from January 2018 to December 2022. Among them, there were 197 males (63.8%) and 112 females (36.2%), with an average age of (66.8±5.5) years old. Based on the delirium diagnostic criteria outlined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, patients were evaluated for postoperative delirium within one week after surgery. They were then divided into a delirium group ( n=75) and a non-delirium group ( n=234). Perioperative indicators potentially related to postoperative delirium, including age, gender, past medical history, tumor characteristics, hematological tests, perioperative sleep disturbances, surgical procedures, intraoperative fluid intake and output, anesthetic dosage, postoperative pain, etc, were collected from the relevant medical record system.Variables with P<0.05 were included in a multivariate Logistic regression model to screen for independent risk factors for delirium. Results:The incidence of delirium after free flap reconstruction surgery for head and neck cancer in elderly patients was 24.3% (75/309). Multivariate Logistic regression analysis showed that male gender ( OR=2.802, P=0.005), perioperative sleep disturbances ( OR=7.104, P<0.001), and moderate-to-severe postoperative pain ( OR=6.903, P<0.001) were risk factors for postoperative delirium. Conclusions:Male gender, perioperative sleep disturbances, and moderate-to-severe postoperative pain are independent risk factors for delirium in these patients.

Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.

Objective:To investigate the safety and feasibility of the domestic single-port serpentine-arm robotic surgical system for pyeloplasty in children with congenital ureteropelvic junction obstruction(UPJO).Methods:Data of UPJO patients who underwent pyeloplasty using a domestic single-port ser-pentine-arm robotic surgical system(Beijing Surgerii Robotics Co.,Ltd.)in Beijing Children's Hospital from November 2023 to February 2024 were retrospectively collected.The patients who were not receiving surgical treatment for the first time,had hydronephrosis caused by other reasons(such as ureterovesical junction obstruction,posterior urethral valve,urinary tract stones,vesicoureteral reflux,ureterocele,etc.),had other urinary tract malformations(such as duplicated kidneys,congenital renal dysplasia,etc.),had severe atrophy of the affected kidney,severe urinary tract infection or severe renal insufficien-cy were excluded.All the surgeries were performed through the umbilicus and abdominal cavity,and the operation time,number of intraoperative incisions,incision size,intraoperative blood loss,and peri-operative complications were recorded.Statistical analysis was performed to compare changes in the an-teroposterior pelvic diameter(APD)and renal cortical thickness before surgery and 6 months postopera-tively.Results:A total of 10 patients were included(8 males and 2 females),with an average age of(10.20±3.12)years.Nine patients were on the left side and one patient was on the right side.The average height was(142.0±17.8)cm and the average weight was(37.6±17.9)kg.All the patients underwent surgery using the domestic single-port robotic surgery system,and no patient was converted to open pyeloplasty.The total operation time was(237±96)min,and the operation time on the operating table was(162.0±69.3)min.The intraoperative blood loss was 5.00(2.25,5.00)mL.No compli-cations,such as bleeding,urine extravasation,fever,and poor wound healing occurred during the perioperative period.Compared with the preoperative measurements,the APD was significantly shortened postoperatively(P=0.005),and the renal cortical thickness significantly increased(P=0.011).Con-clusion:The domestic single-port serpentine arm robotic surgical system is safe and feasible for UPJO pyeloplasty in children,with good surgical results,and can be promoted and applied in most domestic medical centers.

Objective:To investigate the safety and feasibility of the domestic single-port serpentine-arm robotic surgical system for pyeloplasty in children with congenital ureteropelvic junction obstruction(UPJO).Methods:Data of UPJO patients who underwent pyeloplasty using a domestic single-port ser-pentine-arm robotic surgical system(Beijing Surgerii Robotics Co.,Ltd.)in Beijing Children's Hospital from November 2023 to February 2024 were retrospectively collected.The patients who were not receiving surgical treatment for the first time,had hydronephrosis caused by other reasons(such as ureterovesical junction obstruction,posterior urethral valve,urinary tract stones,vesicoureteral reflux,ureterocele,etc.),had other urinary tract malformations(such as duplicated kidneys,congenital renal dysplasia,etc.),had severe atrophy of the affected kidney,severe urinary tract infection or severe renal insufficien-cy were excluded.All the surgeries were performed through the umbilicus and abdominal cavity,and the operation time,number of intraoperative incisions,incision size,intraoperative blood loss,and peri-operative complications were recorded.Statistical analysis was performed to compare changes in the an-teroposterior pelvic diameter(APD)and renal cortical thickness before surgery and 6 months postopera-tively.Results:A total of 10 patients were included(8 males and 2 females),with an average age of(10.20±3.12)years.Nine patients were on the left side and one patient was on the right side.The average height was(142.0±17.8)cm and the average weight was(37.6±17.9)kg.All the patients underwent surgery using the domestic single-port robotic surgery system,and no patient was converted to open pyeloplasty.The total operation time was(237±96)min,and the operation time on the operating table was(162.0±69.3)min.The intraoperative blood loss was 5.00(2.25,5.00)mL.No compli-cations,such as bleeding,urine extravasation,fever,and poor wound healing occurred during the perioperative period.Compared with the preoperative measurements,the APD was significantly shortened postoperatively(P=0.005),and the renal cortical thickness significantly increased(P=0.011).Con-clusion:The domestic single-port serpentine arm robotic surgical system is safe and feasible for UPJO pyeloplasty in children,with good surgical results,and can be promoted and applied in most domestic medical centers.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Objective:To investigate the risk factors for delirium after free flap reconstruction surgery in elderly patients with head and neck cancer.Methods:This study retrospectively collected clinical data from 309 elderly patients with head and neck cancer who underwent radical resection and free flap reconstruction surgery in the Department of Operation & Anesthesiology, College & Hospital of Stomatology, Guangxi Medical University from January 2018 to December 2022. Among them, there were 197 males (63.8%) and 112 females (36.2%), with an average age of (66.8±5.5) years old. Based on the delirium diagnostic criteria outlined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, patients were evaluated for postoperative delirium within one week after surgery. They were then divided into a delirium group ( n=75) and a non-delirium group ( n=234). Perioperative indicators potentially related to postoperative delirium, including age, gender, past medical history, tumor characteristics, hematological tests, perioperative sleep disturbances, surgical procedures, intraoperative fluid intake and output, anesthetic dosage, postoperative pain, etc, were collected from the relevant medical record system.Variables with P<0.05 were included in a multivariate Logistic regression model to screen for independent risk factors for delirium. Results:The incidence of delirium after free flap reconstruction surgery for head and neck cancer in elderly patients was 24.3% (75/309). Multivariate Logistic regression analysis showed that male gender ( OR=2.802, P=0.005), perioperative sleep disturbances ( OR=7.104, P<0.001), and moderate-to-severe postoperative pain ( OR=6.903, P<0.001) were risk factors for postoperative delirium. Conclusions:Male gender, perioperative sleep disturbances, and moderate-to-severe postoperative pain are independent risk factors for delirium in these patients.