Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Objective To explore the effect of follow-up management based on the digital information platform on the compliance of early screening and follow-up of liver cancer in patients with chronic liver diseases,and to provide a management method for clinical practice.Methods Convenience sampling was adopted to include 3,959 patients who had chronic liver diseases and visited the outpatient clinic of the Department of Infectious Liver Diseases in our hospital from January 2022 to December 2023.Before the application of the digital information platform for management,it was the medical staff of the Infectious Liver Disease Department who conducted telephone follow-ups and handwritten registrations for patients with chronic liver diseases within one week after their visits.After management,A liver cancer prediction model installed in the digital information platform of the hospital automatically collected data of the patients,including information about the diseases and results of examinations for intelligent risk stratification of liver cancer.The nurses who were in charge of the follow-up performed individualised follow-up reviews based on the levels of risk.Follow-up re-visit rate of the patients in very high-and high-risks were calculated.Scores of chronic disease self-efficacy and medication compliance were compared before and at 3 months after the follow-up management.Results A total of 3,860 patients completed the study.After the follow-up management,the total follow-up re-visit rate of the patients was 88.2%(1,818/2,062)and that of the high-risk patients was 95.3%(246/258)in 2022,while those in 2023 were 94.0%(1,691/1,798)and 98.3%(232/236),respectively.After 3 months of follow-up management,scores for medication compliance and chronic disease self-efficacy showed significant improvement in comparison with those before the implementation of follow-up management(P<0.001).Conclusion The follow-up management based on a digital information platform is suitable for screening of early liver cancer in the patients with chronic liver diseases,as it improves the re-visit rate of patients for follow-up,medication compliance and self-efficacy.

This paper summarizes clinical experience in treating depression with a combined approach of acupuncture and herbal medicine under the guiding principle of deficiency and excess. Given the complex pathogenesis of depression， it is proposed that syndrome differentiation based on deficiency and excess should serve as the overarching principle. Acupuncture is prioritized， supplemented by Chinese herbal medicine. Acupuncture is based on the spirit-regulating protocol； for excess syndromes， it is combined with the calming and restoring protocol， while for deficiency syndromes， it is combined with the five zang organs tonification protocol. In cases of mixed deficiency and excess， the two protocols are alternated， and adjustments are made dynamically throughout the treatment based on syndrome evolution. Herbal prescriptions are also guided by the differentiation of deficiency and excess. For excess patterns， dispersion and clearance should be emphasized， focusing on soothing the liver， clearing heat， relieving irritability， regulating qi， transforming phlegm， and calming the mind； for deficiency patterns， tonification is emphasized， aiming to strengthen the spleen， nourish the blood， calm the spirit， tonify qi， and consolidate the root.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

Objective To explore the effect of follow-up management based on the digital information platform on the compliance of early screening and follow-up of liver cancer in patients with chronic liver diseases,and to provide a management method for clinical practice.Methods Convenience sampling was adopted to include 3,959 patients who had chronic liver diseases and visited the outpatient clinic of the Department of Infectious Liver Diseases in our hospital from January 2022 to December 2023.Before the application of the digital information platform for management,it was the medical staff of the Infectious Liver Disease Department who conducted telephone follow-ups and handwritten registrations for patients with chronic liver diseases within one week after their visits.After management,A liver cancer prediction model installed in the digital information platform of the hospital automatically collected data of the patients,including information about the diseases and results of examinations for intelligent risk stratification of liver cancer.The nurses who were in charge of the follow-up performed individualised follow-up reviews based on the levels of risk.Follow-up re-visit rate of the patients in very high-and high-risks were calculated.Scores of chronic disease self-efficacy and medication compliance were compared before and at 3 months after the follow-up management.Results A total of 3,860 patients completed the study.After the follow-up management,the total follow-up re-visit rate of the patients was 88.2%(1,818/2,062)and that of the high-risk patients was 95.3%(246/258)in 2022,while those in 2023 were 94.0%(1,691/1,798)and 98.3%(232/236),respectively.After 3 months of follow-up management,scores for medication compliance and chronic disease self-efficacy showed significant improvement in comparison with those before the implementation of follow-up management(P<0.001).Conclusion The follow-up management based on a digital information platform is suitable for screening of early liver cancer in the patients with chronic liver diseases,as it improves the re-visit rate of patients for follow-up,medication compliance and self-efficacy.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Objective To investigate the distribution of B cells in both tumor and non-tumor tissues of gastric cancer patients,analyze their phenotypic characteristics and explore the impact on T cell proliferation.Methods Immunohistochemical staining was utilized to detect the expression of B cell surface marker CD 19 in tumor and non-tumor tissues from 33 gastric cancer patients.The expression levels of chemokine receptors and immunoglobulin molecules on B cells in both tumor and non-tumor tissues were measured using flow cytometry.Chemotaxis experiments were conducted to examine the role of the CXCL12-CXCR4 axis in B cell chemotaxis.B cells isolated and purified from both tissue types were co-cultured with autologous peripheral T cells to assess their effect on T cell proliferation.Results There were significantly more B cells infiltrated in tumor tissues than those infitrated in the non-tumor tissues of gastric cancer patients(P＜0.01),and CXCR4 was highly expressed on tumor-infiltrating B cells compared with B cells derived from non-tumor tissues(P＜0.05).The Cancer Genome Atlas(TCGA)analysis indicated that the expression level of CXCL12 in tumor tissues was positively correlated with the expression level of CD19 in gastric cancer patients(r=0.15,P＜0.01).And the expression level of CXCL12 in tumor tissues of the gastric cancer patients was also positively correlated with the number of B cells infiltrated in tumor tissues.Chemotaxis experiments confirmed that the CXCL12-CXCR4 axis was involved in promoting B cell chemotaxis(P＜0.05).Although B cells in tumor and non-tumor tissues had similar levels of IgM,IgG,and IgA expression,tumor-infiltrating B cells significantly inhibited the proliferation of T cells when compared with B cells derived from non-tumor tissues(P＜0.01).Conclusion There are more B cells infiltrated in gastric cancer tissues,which may be recruited to tumor tissues through the CXCL12-CXCR4 axis,and then inhibit T cell proliferation to promote the progression of gastric cancer.

Objective:To investigate the clinical value of deep learning model based on contrast enhanced ultrasound (CEUS) video in the differential diagnosis of benign and malignant liver tumors.Methods:Between May 2010 and June 2022, 1 213 patients who underwent CEUS examination for liver masses in the Affiliated Hospital of Southwest Medical University were retrospectively collected, and the enrolled patients were divided into training and independent test cohorts with December 31, 2021 as the time cut-off. In the training cohort, the TimeSformer algorithm was used as the infrastructure, and multiple fixed-time segments were obtained from CEUS arterial videos by using the sliding window of the video, and the classification results of the entire video were obtained after fusing the features of multiple segments, so as to build a deep learning model based on CEUS videos. In the independent test cohort, ROC curves were used to verify the validity of the model and compared with three radiologists with different CEUS experience (R1, R2, and R3, with 3, 6, and 10 years of CEUS experience, respectively).Results:A total of 1 213 patients with liver masses were included in the study, including 1 066 patients in the training cohort (426 cases of malignancy) and 147 patients in the independent test cohort (50 cases of malignancy). The area under curve (AUC)value of deep learning model was 0.93±0.01 in the training cohort and 0.89±0.01 in the independent test cohort, and the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 80.42%, 74.19%, 92.00%, 94.52% and 65.71%, respectively. Among the three radiologists, R1 had the lowest diagnostic performance, with accuracy, sensitivity, specificity, PPV and NPV of 67.83%, 51.61%, 98.00%, 97.96% and 52.13%, respectively, while the above indicators of R3 were 82.52%, 76.36%, 94.00%, 95.95% and 68.12%, respectively. McNemar′s test showed that the difference between R1 and the deep learning model was statistically significant ( P<0.001), while the differences between R2 and R3 and the deep learning model were not statistically significant ( P=0.720, 0.868). In addition, the analysis time of the model for a single case was (340.24±16.32)ms, while the average analysis time of radiologists was 62.9 s. Conclusions:The deep learning model based on CEUS can better identify benign and malignant liver masses, and may reach the diagnostic level of experienced radiologists.

AIM: To analyze the research status and future development trends of intermittent exotropia(IXT)by bibliometric study.METHODS: Bibliometrics methods were used and the related literatures in the Web of Science Core Collection(WoSCC)database from 2003 to 2022 were retrieved. CiteSpace6.2.R2 software was used to conduct visualized analysis of publications of one year, countries, institutions, journals, authors, references and keywords.RESULTS: A total of 620 literatures on IXT were retrieved from 2003 to 2022, and there has been a progressive increase in the number of publications. South Korea and the United States, Mayo Clinc and Holmes JM were the most productive and impactful country, institution and author, respectively. The Journal of American Association for Pediatric Ophthalmology and Strabismus(J AAPOS)published the most manuscripts(78 publications). The keywords with the strongest citation burst were surgery, epidemiology, alignment and recurrence.CONCLUSION: Visualized analysis conducted by CiteSpace software could objectively show the quantity changes and distribution of literatures on IXT from 2003 to 2022. Furthermore, the research hotspot of IXT has gradually shifted from surgery and epidemiology to fusion and recurrence.