Objective To explore the effect of task-oriented training of intelligent mirror gloves combined with low-frequency repeti-tive transcranial magnetic stimulation(rTMS)on hand function recovery in stroke patients. Methods From October 1st,2022 to June 30th,2023,136 stroke patients in Northern Jiangsu People's Hospital were ran-domly divided into control group,mirror group,rTMS group and combination group,with 34 patients in each group.All the groups received routine rehabilitation treatment.In addition,the mirror group received task-orient-ed training of intelligent mirror gloves,rTMS group received low-frequency rTMS,and the combination group received task-oriented training combined with low-frequency rTMS,for four weeks.The Fugl-Meyer Assess-ment-Upper Extremities(FMA-UE)score,Wolf Motor Function Test(WMFT)score,and surface electromyo-graphic root mean square(RMS)of forearm extensor and flexor muscle groups on the affected/healthy side be-fore and after treatment were compared.And the differences of transcranial magnetic stimulation-motor-evoked potentials(MEP)between rTMS group and combination group before and after treatment were also compared. Results Four cases in the control group,seven in the mirror group,five in rTMS group and six in the combination group dropped off.The intra-group effect(F>996.656,P<0.001),inter-group effect(F>20.333,P<0.001)and inter-action effect(F>72.796,P<0.001)were significant in the scores of FMA-UE and WMFT,and the RMS ratio of forearm extensor and flexor muscle groups among four groups,in which the combination group was the best.After treatment,the amplitude of MEP increased in rTMS group and combination group(|t|>3.842,P<0.05),and was higher in the combination group than in rTMS group(t=-3.060,P<0.01). Conclusion The task-oriented training of intelligent mirror gloves combined with low-frequency rTMS could effectively promote the recovery of hand function in stroke patients.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

The current treatment strategy for rectal cancer is a comprehensive treatment centered on surgery. The application of total mesorectal excision (TME) has significantly reduced the local recurrence rate and improved the survival prognosis, but a series of pelvic organ dysfunction caused by pelvic autonomic nerve injury during the operation will reduce the postoperative quality of life of patients. Pelvic autonomic nerve preserving (PANP) radical proctectomy has emerged, but the biggest challenge in the implementation process of this technology is the accurate identification of nerves. A series of studies have shown that pelvic intraoperative autonomic monitoring (pIONM) can effectively assist surgeons to identify nerves, The purpose of this article is to introduce the function of pelvic autonomic nerve, the clinical manifestation of postoperative pelvic dysfunction and its relationship with nerve injury, the key points of implementing PANP, and the current situation and research progress of pIONM technology application.

The current treatment strategy for rectal cancer is a comprehensive treatment centered on surgery. The application of total mesorectal excision (TME) has significantly reduced the local recurrence rate and improved the survival prognosis, but a series of pelvic organ dysfunction caused by pelvic autonomic nerve injury during the operation will reduce the postoperative quality of life of patients. Pelvic autonomic nerve preserving (PANP) radical proctectomy has emerged, but the biggest challenge in the implementation process of this technology is the accurate identification of nerves. A series of studies have shown that pelvic intraoperative autonomic monitoring (pIONM) can effectively assist surgeons to identify nerves, The purpose of this article is to introduce the function of pelvic autonomic nerve, the clinical manifestation of postoperative pelvic dysfunction and its relationship with nerve injury, the key points of implementing PANP, and the current situation and research progress of pIONM technology application.

This article is a summary of the Second China Breast Milk Science Conference, which was held in Beijing from August 5 to 7, 2022, with the theme of "Data sharing, method sharing and science sharing". The purpose of the conference is to summarize the latest progress in breast milk research, identify the unresolved issues, and jointly discuss the direction of future breast milk research. Firstly, we summarize the contents and purpose of breast milk scientific research and prospect of breast milk science. The second part focuses on the research status of breast milk composition and its health effects, and puts forward the future research direction. The third section focuses on the health effects of breastfeeding and scientific support and key aspects of breastfeeding promotion actions. The fourth part elaborates the specific methods of current scientific research of breast milk and emphasize the importance of method standardization and the idea of future methodological research. The fifth part consists of the strategy of feeding infants with medical conditions and ways to better promote the growth and development of these infants. The last part introduces the innovation, deficiencies, and future research directions of infant formula production technology in China. This conference demonstrate the importance of multidisciplinary communication, discussions and collaborations in clinical medicine, nutrition, perinatal health, food science, and policy-making in the scientific research of breast milk, and provides guidance for future multidisciplinary research on the physiology of lactation, the composition of breast milk, breastfeeding, and infants and young children nutrition.

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

Objective: To evaluate the indications, safety, feasibility, and surgical technique for patients with head and neck cancers undergoing transoral robotic retropharyngeal lymph node (RPLN) dissection. Methods: The current study enrolled 12 consecutive head and neck cancer patients (seven males and four females) who underwent transoral robotic RPLN dissection with the da Vinci surgical robotic system at the Sun Yat-sen University Cancer Center from May 2019 to July 2020. Seven patients were diagnosed as nasopharyngeal carcinoma with RPLN metastasis after initial treatments, 4 patients were diagnosed as thyroid carcinoma with RPLN metastasis after initial treatments, and one patient was diagnosed as oropharyngeal carcinoma with RPLN metastasis before initial treatments. The operation procedure and duration time, intraoperative blood loss volume and complications, nasogastric feeding tube dependence, tracheostomy dependence, postoperative complications, and hospitalization time were recorded and analyzed. Results: All patients were successfully treated by transoral robotic dissection of the metastatic RPLNs, none of which was converted to open surgery. RPLNs were completely resected in 10 patients, and partly resected in 2 patients (both were nasopharyngeal carcinoma patients). The mean number of RPLN dissected was 1.7. The operation duration time and intraoperative blood loss volume were (191.3±101.1) min and (150.0±86.6) ml, respectively. There was no severe intraoperative complication such as massive haemorrhage or adjacent organ injury during surgery. Nasogastric tube use was required in all patients with (17.1±10.6) days of dependence, while tracheotomy was performed in 8 patients with (11.6±10.7) days of dependence. The postoperative hospitalization stay was (8.5±5.7) days. Postoperative complications occurred in 4 patients, including 2 of retropharyngeal incision and 2 of dysphagia. During a follow-up of (6.5±5.1) months, disease-free progression was observed in all patients, 10 patients were disease-free survival and other 2 patients were survival with tumor burden. Conclusions: The transoral robotic RPLN dissection is safety and feasible. Compared with the traditional open surgical approach, it is less traumatic and safer, has fewer complications and good clinical application potentiality. The indications for transoral robotic RPLN dissection include thyroid carcinoma, oropharyngeal carcinoma, and some selected nasopharyngeal carcinoma and other head and neck cancers. Metastatic RPLNs from some nasopharyngeal carcinoma with incomplete capsule, unclear border and adhesion to the surrounding vessels are not suitable for transoral robotic RPLN dissection.
Blood Loss, Surgical ; Female ; Head and Neck Neoplasms/pathology* ; Humans ; Lymph Node Excision/methods* ; Lymph Nodes/pathology* ; Male ; Nasopharyngeal Carcinoma/pathology* ; Nasopharyngeal Neoplasms/surgery* ; Neck Dissection/methods* ; Postoperative Complications/surgery* ; Robotic Surgical Procedures/methods* ; Thyroid Neoplasms/pathology*

Objective: To evaluate the therapeutic and prognostic outcomes of transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OSCC). Methods: A retrospective study of 99 OSCC patients treated with TORS in Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center between April 2017 and May 2021 was conducted. There were 84 males and 15 females, with an age range of 35-85 years. Patients' clinical characteristics, including clinical staging, HPV infection status, perioperative management and postoperative adjuvant treatment, were recorded. The overall survival (OS) and progression-free survival (PFS) were analyzed. The survival outcomes were analyzed with Kaplan-Meier method and Log-rank test. Results: The hospital stay of OSCC patients with TORS was (5.3±2.9) days and the average time of postoperative nasal feeding tube indwelling was (15.2±10.8) days. Among the 99 patients, 21 (21.2%) received tracheotomy and the average time of tracheotomy tube indwelling was (11.9±11.4) days. The two-year OS and PFS in patients with follow-up over two years were 94.0% and 87.7%, respectively and the three-year OS and PFS of patients with follow-up over three years were 94.0% and 78.9%, respectively. The two-year OS and PFS were respectively 97.4% and 88.9%, for patients with stages I-II and 86.8% and 88.9% for patients with stages III-IV. HPV-negative and HPV-positive patients had respectively two-year OS (100.0% vs. 91.5%) and PFS (88.9% vs. 87.2%). There was no significantly statistical difference in survival between patients with and without adjuvant radiotherapy after TORS (82.6% vs. 90.5%, HR=0.52, 95%CI: 0.12-2.23, P=0.400). Conclusions: TORS is more suitable for the treatment of patients with early (Ⅰ-Ⅱ) or HPV-positive oropharyngeal squamous cell carcinoma, and the recovery after TORS treatment is good.
Adult ; Aged ; Aged, 80 and over ; Female ; Head and Neck Neoplasms ; Humans ; Male ; Middle Aged ; Oropharyngeal Neoplasms/surgery* ; Papillomavirus Infections/surgery* ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Squamous Cell Carcinoma of Head and Neck/surgery* ; Treatment Outcome

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective: To explore the therapeutic effects of transoral robotic surgery (TORS) and traditional surgical modes in oropharyngeal squamous cell carcinoma (OPSCC). Methods: The clinicopathological data of patients with oropharyngeal squamous cell carcinoma treated at Sun Yat-sen University Cancer Center from 2010 to 2018 were retrospectively analyzed. 135 cases were treated with traditional surgery (non-TORS group), while 52 cases were treated with TORS (TORS group). The prognosis of the two groups of patients were analyzed by Kaplan-Meier method and Log rank test, the influencing factors were analyzed by Cox regression model. Results: The 2-year overall survival (OS, 94.2%) and 2-year progression-free survival (PFS, 93.8%) of patients in the TORS group were better than those in the non-TORS group (71.4% and 71.4%, respectively, P<0.05). The 2-year OS (93.3%) and 2-year PFS (92.8%) of TORS group patients in T1-2 stage were better than those of non-TORS group (73.1% and 72.8%, respectively, P<0.05). The 2-year OS (95.8%) and 2-year PFS (95.2%) of patients with stage Ⅰ to Ⅱ in the TORS group were not significantly different from those in the non-TORS group (84.1% and 83.9%, respectively, P>0.05). The 2-year OS (92.9%) and 2-year PFS rate (92.7%) of patients with stage Ⅲ to Ⅳ in the TORS group were better than those in the non-TORS group (64.7% and 63.9%, respectively, P<0.05). The 2-year OS (94.4%) of HPV-positive patients in the TORS group was not significantly different from that in the non-TORS group (83.3%, P=0.222). The 2-year OS of HPV-negative patients in the TORS group (94.1%) was significantly different from that in the non-TORS group (43.7%, P<0.001). HPV status was an independent prognostic factor (P=0.008). Conclusions: TORS has a better prognosis in the treatment of oropharyngeal squamous cell carcinoma compared with the traditional treatment methods. The patients with T1-T2 can achieve better survival benefits after TORS treatment. The HPV-positive OPSCC patients has a better prognosis than that of HPV-negative OPSCC patients, and regardless of HPV status, OPSCC patients in the TORS group could obtain a better survival prognosis.
Head and Neck Neoplasms ; Humans ; Oropharyngeal Neoplasms/surgery* ; Papillomavirus Infections/complications* ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Squamous Cell Carcinoma of Head and Neck/surgery*