[Analysis of risk factors associated with postoperative pancreatic fistula after robotic-assisted distal pancreatectomy].

Objective: To investigate pertinent risk factors for postoperative pancreatic fistula(POPF) after robotic-assisted distal pancreatectomy(RDP). Methods: This is a retrospective cohort study. Clinical data of 1 211 patients who underwent various methods of distal pancreatectomy at the Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,between January 2021 and December 2023 were retrospectively collected. Among the study participants,440 cases were in the robot-assisted group(173 males and 267 females),with an age(M(IQR)) of 55(29)years;720 cases were in the open surgery group (390 males and 330 females),with an age of 64(15)years;and 51 cases were in the laparoscopic group(17 males and 34 females),with an age of 56(25)years. These 440 patients who underwent RDP were divided into two cohorts based on the presence of clinically relevant pancreatic fistulas(grades B and C). Univariate and multivariate analysis were performed on 27 factors related to POPF. Univariate analysis methods included independent sample t-test,Mann-Whitney U test,and χ2 test,while multivariate analysis utilized binary logistic regression. Results: After stratification by pathological type,there was no significant difference in the incidence of pancreatic fistula between the robot-assisted group and the open surgery group(benign tumor:χ2=1.200,P=0.952;malignant tumor:χ2=0.391,P=0.532). The surgical duration of the RDP group (Z1=15.113,P1<0.01; Z2=4.232, P2<0.01) was significantly shorter than that of the open surgery and laparoscopic groups,so as the intraoperative blood loss (Z1=12.530,P1<0.01;Z2=2.550,P2=0.032). Postoperative hospital stay in the RDP group was significantly shorter than that in the open surgery group (Z1=10.947, P1<0.01), but not different from that in the laparoscopic group (P2>0.05). All 440 patients underwent successful surgery,of which there was only 1 case who underwent a conversion to open surgery. A total of 104 patients(23.6%) developed clinically relevant pancreatic fistulas,and no perioperative mortality was observed. Univariate analysis revealed that 6 factors were associated with POPF after RDP: gender(χ2=12.048,P=0.001),history of smoking (χ2=6.327,P=0.012),history of alcohol consumption (χ2=17.597,P<0.01),manual pancreas division (χ2=9.839,P=0.002),early elevation of amylase in drainage fluid (Z=5.187,P<0.01),and delayed gastric emptying (χ2=4.485,P=0.034). No statistically significant association with POPF was found for the remaining factors(all P>0.05).The cut-off value for the early amylase level in the drainage fluid was determined to be 7 719.5 IU/ml,with an area under curve of 0.676 determined by receiver operating characteristic curve analysis. Binary logistic regression analysis identified a history of alcohol consumption(P=0.002,95%CI:0.112 to 0.623),manual pancreas division(P=0.001,95%CI:1.446 to 4.082),early amylase level of drainage fluid ≥7 719.5 IU/ml(P<0.01,95%CI:0.151 to 0.438),and delayed gastric emptying(P=0.020,95%CI:1.131 to 4.233) as independent risk factors for POPF of RDP. Conclusions: Patients with pancreatic body and tail tumors who receive RDP therapy are at increased risk of developing a pancreatic fistula if they have a history of alcohol consumption,manual pancreas division,early elevation of amylase in drainage fluid to ≥7 719.5 IU/ml, or delayed gastric emptying.

[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

[MiR-132-3p negatively regulates CAMTA1 to promote Schwann cell proliferation and migration and alleviates I-125 seeds-induced exacerbation of facial nerve injury in rats].

OBJECTIVE: To investigate the regulatory effect of miR-132-3p on calmodulin-binding transcription activator 1 (CAMTA1) and Schwann cell activity in rats with facial nerve injury (FNI) treated with I-125 seeds. METHODS: Rat Schwann cells were irradiated with I-125 seeds and transfected with miR-132-3p mimic, miR-132-3p inhibitor or sh-CAMTA1. The expressions of S100B and ß-tubulin Ⅲ in the cells were detected with immunofluorescence assay, and the expressions of miR-132-3p and CAMTA1 protein were determined using RT-qPCR and Western blotting, respectively. EdU staining and Transwell assay were used to evaluate the changes in cell proliferation and migration ability. In a rat model of FNI, I-125 seeds were implanted into the facial tissues near the facial nerve 2 weeks before modeling, and miR-132-3p mimic was injected subcutaneously in the face after modeling. The pathologies of the facial nerve was assessed by HE, LFB and immunofluorescence staining. The targeting relationship between miR-132-3p and CAMTA1 was verified using StarBase v2.0 database and dual-luciferase reporter assay. RESULTS: Rat Schwann cells showed high expressions of S100B and ß-tubulin Ⅲ. I-125 seeds radiation significantly decreased miR-132-3p expression and repressed proliferation and migration of the cells (P < 0.001). Overexpression of miR-132-3p or CAMTA1 knockdown obviously enhanced proliferation and migration of the Schwann cells, while miR-132-3p knockdown produced the opposite effect. MiR-132-3p negatively regulated CAMTA1 expression. In the rat models of FNI, miR-132-3p injection significantly inhibited CAMTA1 expression and attenuated I-125 seeds-induced exacerbation of FNI. CONCLUSION: Overexpression of miR-132-3p suppresses CAMTA1 expression and promotes Schwann cell proliferation and migration to alleviate I-125 seeds-induced exacerbation of FNI in rats.

Comparison of clinical data between the proximal femoral bionic nail (PFBN) and hip replacement for the treatment of femoral intertrochanteric fracture.

OBJECTIVE: The aim of this study was to compare the difference between proximal femoral bionic nail (PFBN) and hip replacement (HR) for femoral intertrochanteric fracture. MATERIALS AND METHODS: A retrospective analysis of the differences in operative time, length of stay, postoperative Harris score, and postoperative mortality between patients with femoral intertrochanteric fracture treated by PFBN and HR admitted to Jinzhai County People's Hospital from October 2020 to September 2022 was performed. RESULTS: A total of 56 patients with femoral intertrochanteric fracture, 26 with PFBN and 30 with HR, were included in the study. There were no differences in the length of surgery, pre- and post-operative hemoglobin, or post-operative Harris score at 3 months between the two groups. Compared to the HR group, the PFBN group had a lower total cost, shorter hospital stays, and lower mortality but a longer ambulation time, with a difference of 3.36 weeks. CONCLUSIONS: PFBN may be a promising new treatment for femoral intertrochanteric fracture.

[Mechanisms and clinical management of small bowel obstruction caused by kinking of the jejunojejunal anastomosis after laparoscopic Roux-en-Y gastric bypass].

Currently, obesity and its complications have become increasingly serious health issues. Bariatric surgery is an effective method of treating obesity and related metabolic complications. Among them, Roux-en-Y gastric bypass (RYGB) is still considered the "gold standard" procedure for bariatric surgery. Small bowel obstruction is one of the possible complications after RYGB, and in addition to the formation of intra-abdominal hernias, kinking of the jejunojejunal anastomosis is an important cause of small bowel obstruction. The early clinical symptoms of kinking of the jejunojejunal anastomosis often lack clarity in the early stages. Therefore, early diagnosis, prevention, and effective treatment of kinking of the jejunojejunal anastomosis are challenging but crucial. The occurrence of kinking of the jejunojejunal anastomosis may be related to surgical techniques and the surgeon's experience. The use of anti-obstruction stitch, mesenteric division, and bidirectional jejunojejunal anastomosis may be beneficial in preventing kinking of the jejunojejunal anastomosis. If kinking of the jejunojejunal anastomosis occurs, timely abdominal CT scans and endoscopic examinations should be performed. Gastric and intestinal decompression should be initiated immediately, and exploratory surgery should be prepared.

[Clinical features and prognostic analysis of checkpoint inhibitor pneumonitis in patients with non-small cell lung cancer].

Objective: To describe the clinical characteristics of patients with non-small cell lung cancer (NSCLC) who developed checkpoint inhibitor pneumonitis (CIP) and to explore potential prognostic factors. Methods: NSCLC patients who were complicated with CIP after immune checkpoint inhibitors (ICIs) therapy in our institute were enrolled in this study from 1 July 2018 to 30 November 2022. Clinical data of NSCLC-CIP patients were collected, including clinical and radiological features and their outcomes. Results: Among the 70 enrolled NSCLC-CIP patients, there were 57 males (81%) and 13 females (19%). The mean age at the diagnosis of CIP was (65.2±6.3) years. There were 46 smokers (66%), 26 patients (37%) with emphysema, 19 patients (27%) with previous interstitial lung disease, and 26 patients (37%) with a history of thoracic radiation. The mean interval from the first application of checkpoint inhibitor to the onset of CIP was (122.7±106.9) days (range: 2-458 days). The main chest CT manifestations were coincided with non-specific interstitial pneumonia (NSIP) pattern and organizing pneumonia (OP) pattern. Most patients had grade 2 (21 cases) or grade 3 (34 cases) CIP. Seventeen patients had been concurrent with other immune-related adverse events such as rash, hepatitis, colitis, and thyroiditis. Half of the enrolled patients (36 patients/51%) had fever, and most patients had elevated C-reactive protein (52 patients/72%) and all patients had elevated erythrocyte sedimentation rate (70 patients/100%). Serum lactate dehydrogenase was elevated in 34 CIP patients. Prednisone≥1 mg·kg-1·d-1 (or equivalent) was the most commonly used initial treatment in CIP patients (50 patients/71.4%). Complications with pulmonary infections (OR=4.44, P=0.03), use of anti-fungal drugs (OR=5.10, P=0.03) or therapeutic dose of sulfamethoxazole (OR=4.86, P=0.04), longer duration of prednisone≥1 mg·kg-1·d-1 (or equivalent) (Z=-2.33, P=0.02) were probable potential risk factors for poor prognosis. Conclusions: Older males with smoking history might be predisposed to develop NSCLC-CIPs after ICIs therapy. NSIP pattern and OP pattern were common chest CT manifestations. Complications with pulmonary infections (especially fungal infection or Pneumocystis jirovecii pneumonia), longer duration, longer duration of high-dose corticosteroids were likely potential risk factors for poor prognosis.

Biomaterials-mediated ligation of immune cell surface receptors for immunoengineering.

A wide variety of cell surface receptors found on immune cells are essential to the body's immunological defense mechanisms. Cell surface receptors enable immune cells to sense extracellular stimuli and identify pathogens, transmitting activating or inhibitory signals that regulate the immune cell state and coordinate immunological responses. These receptors can dynamically aggregate or disperse due to the fluidity of the cell membrane, particularly during interactions between cells or between cells and pathogens. At the contact surface, cell surface receptors form microclusters, facilitating the recruitment and amplification of downstream signals. The strength of the immune signal is influenced by both the quantity and the specific types of participating receptors. Generally, receptor cross-linking, meaning multivalent ligation of receptors on one cell, leads to greater interface connectivity and more robust signaling. However, intercellular interactions are often spatially restricted by other cellular structures. Therefore, it is essential to comprehend these receptors' features for developing effective immunoengineering approaches. Biomaterials can stimulate and simulate interactions between immune cells and their targets. Biomaterials can activate immune cells to act against pathogenic organisms or cancer cells, thereby offering a valuable immunoengineering toolset for vaccination and immunotherapy. In this review, we systematically summarize biomaterial-based immunoengineering strategies that consider the biology of diverse immune cell surface receptors and the structural attributes of pathogens. By combining this knowledge, we aim to advance the development of rational and effective approaches for immune modulation and therapeutic interventions.

[Effects of cognition-related lifestyles on early cognitive decline in community older adults in China].

Objective: To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline. Methods: The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline. Results: In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 (OR=0.683, 95%CI: 0.457-1.019; OR=0.623, 95%CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 (OR=0.491, 95%CI: 0.297-0.812; OR=0.556, 95%CI: 0.332-0.929; trend P=0.024). Conclusion: Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

[Surgical strategies and efficacy analysis for aortic dissection complicating intractable mesenteric artery ischemia].

Objective: To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia. Methods: This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded. Results: Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%. Conclusions: Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.

Three-dimensional bone remodelling of glenoid fossa in patients with skeletal Class III malocclusion after bimaxillary orthognathic surgery.

This study aimed to characterize three-dimensional quantitative morphological changes of glenoid fossa in patients with skeletal Class III malocclusion treated with bimaxillary orthognathic surgery. Ninety-five eligible patients (50 male, 45 female; mean age 22.09 years) were enrolled retrospectively. Cone beam computed tomography obtained at 1 week preoperatively (T0), immediately after surgery (T1), and at ≥ 12 months postoperatively (T2) were registered based on cranial base using voxel-based registration in 3D Slicer. Glenoid fossa surface was divided spatially into four regions, and bone modelling in these regions was visualized with color maps. Our data revealed that the mean surface variations of glenoid fossa were small, with modest bone formation as a whole. No significant associations between anteroposterior or vertical mandibular displacement and overall glenoid fossa remodeling were found (P > 0.05). Moreover, bone deposition was frequently observed in the anterior-lateral region of glenoid fossa in patients with a larger mandibular movement during T0-T1 (P < 0.001). Paired bone formation in the anterior-lateral region of glenoid fossa and bone resorption in the anterior-lateral region of condylar head was frequently observed. Collectively, our results revealed that glenoid fossa underwent complex but modest bone remodeling after bimaxillary surgery in skeletal Class III patients.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Penpulimab combined with anlotinib in patients with R/M HNSCC after failure of platinum-based chemotherapy: a single-arm, multicenter, phase â ¡ study.

BACKGROUND: Treatment regimens for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after failure of platinum-based chemotherapy have been illustrated with limited efficacy. PATIENTS AND METHODS: Here, we report a single-arm, multicenter, phase Ⅱ study of R/M HNSCC patients treated with a programmed cell death-1 antibody penpulimab (200 mg) and anlotinib (12 mg) after failing at least one line of platinum-based chemotherapy. RESULTS: Of 38 patients in total, 13 (34.21%) patients achieved partial response and 16 (42.11%) patients achieved stable disease. After a median follow-up of 7.06 months (range: 4.14-15.70 months), the independent review committee-assessed objective response rate was 34.21%, the disease control rate was 76.32%. The median progression-free survival was 8.35 months (95% confidence interval 5.95-13.11 months). Twelve patients died and the median overall survival (OS) was not reached. The 12-month OS rate was 59.76%. Grade 3/4 treatment-related adverse events occurred in 47.37% of the patients. CONCLUSION: Penpulimab combined with anlotinib demonstrated promising efficacy and manageable safety in R/M HNSCC patients after failure of platinum-based chemotherapy.

TLR4-MyD88-NF-κB signaling imbalances Th17 and Treg cells in thymoma with myasthenia gravis.

OBJECTIVE: Thymus is an immune organ in which pathological changes may cause autoimmune diseases, including myasthenia gravis (MG). Recent studies have focused on Toll-like receptor 4 (TLR4) signaling as the cause of such changes. In our previous study, an imbalance of T helper 17 (Th17) cells and T regulatory (Treg) cells was found in MG thymoma. These results suggest the involvement of TLR4 in the pathogenesis of thymoma MG via an alteration of the Th17/Treg balance. Here, we aimed to assess whether the TLR4-MyD88-NF-κB pathway is upregulated in MG thymoma and its relationship with Th17/Treg cells. PATIENTS AND METHODS: We collect thymoma samples from 54 patients with or without MG, detecting the expression level of TLR4, MyD88, and NF-κB in thymoma tissues. Next, we established an in vitro experiment of coculturing thymoma cells with CD4+ T cells and detected the differentiation of Th17 cells and Treg cells and their marker protein, retinoid-related orphan receptor gamma t (RORγt) and forkhead transcription factor 3 (Foxp3). RESULTS: We found TLR4, MyD88, and NF-κB expressed more in MG thymoma compared with simple thymoma. After the transwell coculturing, we observed an imbalance of Th17/Treg cells after TLR4 stimulation. CONCLUSIONS: TLR4 is stimulated in thymoma, causing an increase of Th17 cells and a decrease of Treg cells, namely an imbalance of Th17/Treg cells, resulting in MG.

[Clinical effects of retrograde anterolateral thigh flaps in repairing anterior knee joint wounds under the concept of precise flap surgery].

Objective: To introduce the methods of retrograde anterolateral thigh flaps in repairing anterior knee joint wounds under the concept of precise flap surgery and to explore the clinical effects. Methods: A retrospective observational study was conducted. From August 2014 to March 2022, 7 patients with anterior knee joint wounds were treated with retrograde anterolateral thigh flap under the guidance of the concept of precise flap surgery in the 920th Hospital of Joint Logistic Support Force of PLA. Among them, 6 were males and 1 was female, aged 36 to 66 years. The sizes of wounds were 7 cm×5 cm to 15 cm×11 cm after debridement. All the patients were performed with computed tomography angiography (CTA), the donor and recipient sites were evaluated according to the precise flap surgery method, and the optimal pedicle, perforator, and pivot of flaps were chosen. The flap sizes were 10 cm×6 cm to 20 cm×9 cm, and all the donor sites of flaps were sutured directly. The consistency of the intraoperative exploration with preoperative CTA was observed. The flap survival and occurrence of complications were observed after surgery. The color, appearance, texture, and occurrence of complications were followed up. At the last follow-up, the blood supply of flaps was evaluated using the blood circulation evaluation indicators of Chinese Medical Association Hand Surgery Branch's trial criteria for digital replantation function evaluation, and the function of knee joint was evaluated using knee joint scoring system of hospital for special surgery. Results: The flap condition of the intraoperative exploration was completely consistent with that of preoperative CTA. The flaps survived completely after surgery in 6 patients, while necrosis at the edge of the flap occurred in 1 patient, which healed after dressing change. All the flaps were hyperperfused after surgery, and the color of the flaps gradually became normal after 1 week. Follow-up of 7 to 44 months showed that the color, appearance, and texture were well in all the patients, while local osteomyelitis at the proximal tibia occurred in 1 patient. At the last follow-up, all the 7 patients had excellent blood circulation; the function score of knee joint was 69 to 91, which was evaluated as excellent in 3 cases, good in 3 cases, and fair in 1 case. Conclusions: The retrograde anterolateral thigh flap has large variations, and the application of precise flap surgery method can accurately understand the variations before surgery, guide the design and cutting of the flaps, thus achieving precise repair of anterior knee joint wounds, with good repair outcome.

[Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study].

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

[JAG1 affects monocytes-macrophages to reshape the pre-metastatic niche of triple-negative breast cancer through LncRNA MALAT1 in exosomes].

OBJECTIVE: To investigate the effect of JAG1 on the activities of monocytes-macrophages in pre-metastatic niche (PMN) of triple-negative breast cancer (TNBC) and explore the possible regulatory mechanism. METHODS: JAG1 expression in human TNBC MDA-MB-231 and MDA-MB-231B cells was detected using quantitative real-time PCR (qRT-PCR).Ten female nude mice were inoculated with MDA-MB-231 cells (n=5) or MDA-MB-231B cells (n=5) in the mammary fat pad, and 6 weeks later, the tumor tissues were collected for immunohistochemistry.Human monocytes THP-1 cells were treated with rhJAG1 or conditioned media (CM) of TNBC MDA-MB-231 and MDA-MB-231B cells to assess the direct effect of JAG1 on monocytes and its effect on monocytes in the PMN using monocyte-endothelial adhesion, Transwell assay, qRT-PCR and Western blotting.Transmission electron microscopy and nanoparticle tracking analyses were used to identify the effect of JAG1 on exosome release from the TNBC cells.MiRNAs interacting with lncRNA MALAT1 were identified by bioinformatics and validated using qRT-PCR. RESULTS: Compared with MDA-MB-231 cells, the invasive strain MDA-MB-231B cells showed significantly higher JAG1 expression and greater liver metastasis potential (P<0.01).Both direct treatment with rhJAG1 and treatment with the conditioned media promoted adhesion and migration and affected differentiation of the monocytes (P<0.05).Transmission electron microscopy and nanoparticle tracking analysis showed that JAG1 strongly enhanced exosome secretion from MDAMB-231 cells (P<0.01) and increased MALAT1 content in the exosomes (P<0.0001).Five candidate miRNAs related to MALAT1 and JAG1 were identified by bioinformatics analysis, and miR-26a-5p was identified as a potential target of MALAT1 in monocytes-macrophages in TMN (P<0.0001). CONCLUSION: JAG1 can promote exocrine secretion of TNBC and increase the expression of MALAT1 to cause targeted downregulation of miR-26a-5p in monocytes-macrophages in the PMN, which in turn increases JAG1 expression in monocytes-macrophages to affect their adhesion, migration and osteoclast differentiation in the PMN.

[Analysis of the common respiratory viruses in children with acute respiratory infection in a hospital in Lanzhou City from 2021 to 2022].

To explore the situation of 8 common respiratory pathogens in children with acute respiratory infection (ARI) from 2021 to 2022.The retrospective study selected 8 710 ARI patients from September 2021 to August 2022 in the Maternal and Child Health Hospital of Gansu Province as the study object, patients aged 0 to 17 years old, including 5 048 male children and 3 662 female children. Indirect immunofluorescence was used to detect 8 common respiratory pathogens, including influenza virus A (FluA), influenza virus B (FluB), parainfluenza virus (PIV), respiratory syncytial virus (RSV), adenovirus (ADV), Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP), and Coxsackie virus group B (CoxB) IgM antibodies. χ2 test was used to analyze the results. The results showed that 1 497 of 8 710 children with ARI were positive, with a positive rate of 17.19%. The detection rate of MP among 8 common respiratory pathogens was 11.34%, accounting for 66.0%, followed by FluB, CoxB, PIV, RSV, ADV, FluA and CP, accounting for 13.83%, 9.55%, 6.01%, 2.61%, 1.47%, 0.40% and 0.13%, respectively. Respiratory tract viruses (FluA, FluB, RSV, ADV, PIV, CoxB) accounted for 33.86%.There were significant differences in the detection rates of PIV, ADV and MP among children of different genders (χ2=6.814, 5.154 and 17.784, P<0.05). The detection rate of school-age children (6-17 years old) was the highest, accounting for 33.27% (184/553). The detection rates of 8 common respiratory pathogens in patients with ARI were higher in spring and winter and lower in summer and autumn. To sum up, from 2021 to 2022, MP and FluB infection were dominant in ARI patients in our hospital. The peak period of 8 common respiratory pathogens was in spring and winter. The physical examination rate of 8 common respiratory pathogens in ARI patients aged 6-17 years old was the highest.