Objective:To report the follow-up status of patients participating phase Ⅲ clinical trial (ZGDD3) of Donafenib tosilate (abbreviated as Donafenib) in the treatment of progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), and to explore its efficacy, safety and prognostic factors.Methods:This study was a randomized controlled trial, and the clinicopathological data and follow-up results of 29 patients (16 males, 13 females, age 40-68 years) who participated in the clinical trial ZGDD3 between August 2018 and March 2021 were analyzed. Patients were divided into Donafenib group and placebo group using the central dynamic randomization method with the ratio of 2∶1. Adverse reactions (AE) during the trial were observed. Independent-sample t test, Mann-Whitney U test and Fisher exact test were used to analyze the differences of baseline characteristics between the two groups. Progression-free survival (PFS) and overall survival (OS) were followed up. Kaplan-Meier method was used to draw the survival curve (log-rank test) and Cox regression analysis was used to analyze the prognostic factors. Results:There were 22 patients in Donafenib group and 7 patients in placebo group. There were no significant differences of baseline characteristics between the two groups ( t values: -0.68, Z values: from -1.47 to -0.56, all P>0.05). The follow-up was 32.07(21.07, 49.85) months. During the trial, drug-related AEs occurred in all patients in Donafenib group, mostly was grade Ⅰ-Ⅱ, no grade Ⅳ or Ⅴ AEs were found. The median PFS was significantly longer in Donafenib group than that in placebo group (13.23 vs 4.03 months; χ2=9.68, P=0.002), and the median OS was 55.00 and 24.30 months respectively ( χ2=2.07, P=0.150). Metastasis to less common sites was the independent risk factor for OS (hazard ratio ( HR)=6.789, 95% CI: 1.272-36.246, P=0.025). Conclusions:Donafenib shows good clinical application in the treatment of RAIR-DTC, demonstrating good safety and efficacy. Metastasis to less common sites is closely related to OS.

OBJECTIVE To evaluate the efficacy and safety of letermovir in preventing cytomegalovirus(CMV)infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT).METHODS A retrospective cohort study was conducted,enrolling patients who underwent allo-HSCT at the Department of Hematology,Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,from August 30,2022,to February 21,2024.Patients who initiated letermovir prophylaxis within 28 days post-transplantation were assigned to the experimental group(99 cases),while those who did not initiate letermovir within this period were assigned to the control group(18 cases).The incidence and clinical characteristics of CMV infection(including the number of CMV infection cases,the number of cases progressing to CMV disease,recurrent CMV disease,onset time of CMV infection,and treatment duration),immune function recovery within 120 days post-transplantation,and the occurrence of transplantation-related complications(including CD4+and CD8+T-cell recovery,Epstein-Barr virus infection,acute graft-versus-host disease,human herpesvirus 6 infection,and posttransplant lymphoproliferative disorders)and adverse events were recorded.Univariate and multivariate Cox regression analyses were performed to identify factors influencing CMV infection.RESULTS A total of 117 patients were included,among whom 15 developed CMV infection,5 progressed to CMV disease,and 2 experienced recurrent CMV disease.The CMV infection rate in the experimental group was significantly lower than that in the control group(P＜0.001),and the onset time of CMV infection was significantly delayed(P=0.014).The proportion of patients with CD4+T-cell counts≥200 cells/μL in the experimental group was significantly lower than that in the control group(P=0.022).During the follow-up period,elevated creatinine levels were observed in 1 patient,and nausea and vomiting were observed in 2 patients.Multivariate Cox regression analysis revealed that the use of high-dose corticosteroids was a risk factor for CMV infection(HR=6.230,95%CI of 1.255-30.926,P=0.025),while initiating letermovir within 28 days post-transplantation was a protective factor(HR=0.125,95%CI of 0.045-0.348,P＜0.001).CONCLUSIONS Early initiation of letermovir after allo-HSCT significantly reduces the CMV infection rate and delays the onset of infection,with favorable short-term safety.

Objective:To report the follow-up status of patients participating phase Ⅲ clinical trial (ZGDD3) of Donafenib tosilate (abbreviated as Donafenib) in the treatment of progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), and to explore its efficacy, safety and prognostic factors.Methods:This study was a randomized controlled trial, and the clinicopathological data and follow-up results of 29 patients (16 males, 13 females, age 40-68 years) who participated in the clinical trial ZGDD3 between August 2018 and March 2021 were analyzed. Patients were divided into Donafenib group and placebo group using the central dynamic randomization method with the ratio of 2∶1. Adverse reactions (AE) during the trial were observed. Independent-sample t test, Mann-Whitney U test and Fisher exact test were used to analyze the differences of baseline characteristics between the two groups. Progression-free survival (PFS) and overall survival (OS) were followed up. Kaplan-Meier method was used to draw the survival curve (log-rank test) and Cox regression analysis was used to analyze the prognostic factors. Results:There were 22 patients in Donafenib group and 7 patients in placebo group. There were no significant differences of baseline characteristics between the two groups ( t values: -0.68, Z values: from -1.47 to -0.56, all P>0.05). The follow-up was 32.07(21.07, 49.85) months. During the trial, drug-related AEs occurred in all patients in Donafenib group, mostly was grade Ⅰ-Ⅱ, no grade Ⅳ or Ⅴ AEs were found. The median PFS was significantly longer in Donafenib group than that in placebo group (13.23 vs 4.03 months; χ2=9.68, P=0.002), and the median OS was 55.00 and 24.30 months respectively ( χ2=2.07, P=0.150). Metastasis to less common sites was the independent risk factor for OS (hazard ratio ( HR)=6.789, 95% CI: 1.272-36.246, P=0.025). Conclusions:Donafenib shows good clinical application in the treatment of RAIR-DTC, demonstrating good safety and efficacy. Metastasis to less common sites is closely related to OS.

BACKGROUND:The effect of electroacupuncture on the proliferation and differentiation of hippocampal oligodendrocytes in model mice with Alzheimer's disease remains poorly understood while demyelinating reaction related to oligodendrocytes is a common pathological reaction of Alzheimer's disease. OBJECTIVE:To investigate the effects and mechanism of electroacupuncture stimulation of"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)in Alzheimer's disease model mice on the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes. METHODS:Forty 6-week-old SPF APP/PS1 transgenic male Alzheimer's disease model mice were randomly divided into electroacupuncture group(n=20)and Alzheimer's disease model group(n=20).Healthy male C57BL/6J mice of the same age were used as normal controls(n=20).The mice in the electroacupuncture group received electroacupuncture at"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)for 16 weeks(20 minutes/day and one day off a week).After electroacupuncture,Morris water maze was used to detect the changes of learning and memory function.Immunohistochemistry was utilized to detect hippocampal dentate gyrus β-amyloid senile plaques.The expression of BrdU/NeuN and BrdU/GALC in the hippocampal dentate gyrus was detected by immunofluorescence double labeling.Western blot assay was used to detect the expression levels of neuron specific protein Nestin and oligodendrocyte specific protein GALC in the hippocampus.mRNA and protein levels of Notch1 and Hes1 in the hippocampus were detected by real-time fluorescence quantitative PCR and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the normal control group,the ability of learning and memory in the Alzheimer's disease model group decreased significantly;hippocampal dentate gyrus β-amyloid senile plaques increased significantly(P<0.01);the expression of GALC and Nestin in the hippocampus decreased significantly(P<0.01,P<0.05).(2)Compared with the Alzheimer's disease model group,the learning and memory ability of the electroacupuncture group was significantly increased;β-amyloid senile plaque in the hippocampal dentate gyrus decreased significantly(P<0.01).BrdU/NeuN double labeled positive cells in the hippocampal dentate gyrus and Nestin protein expression in the hippocampus increased significantly(P<0.01,P<0.05);GALC expression in hippocampus increased significantly(P<0.01).The mRNA and protein levels of Notch1 in the hippocampus were significantly increased(P<0.05,P<0.01).The mRNA and protein levels of Hes1 in the hippocampus decreased significantly(P<0.05).(3)These findings indicate that electroacupuncture at"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)of the Alzheimer's disease model infant mice can promote the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes,which may be regulated through the Notch1/Hes1 pathway.

Objective To investigate the effect and mechanism of HHQ 16, a derivative of astragaloside Ⅳ, on hepatocyte lipid accumulation. Methods Free fatty acids were used to stimulate lipid hepatocyte accumulation. Triglyceride and Oil Red O staining were detected to reflect hepatocyte lipid accumulation. The expression of α1-acidglycoprotein （ORM） and its regulators were detected by real-time quantitative PCR and immunoblotting. The expression of ORM1 was interfered with siRNA to determine whether it mediated the action of HHQ16.The expression of ORM1 was interfered by siRNA to determine whether it mediated the action of HHQ16. Results HHQ16 significantly ameliorated FFA-induced hepatocyte lipid deposition. HHQ16 elevated ORM expression, and the protective effect of HHQ16 on hepatocyte lipid accumulation was reversed by ORM interference. Conclusion HHQ16 could ameliorate hepatocyte lipid accumulation by elevating ORM.

Objective:To explore the value of serum inflammation-related indicators in predicting the effect of neoadjuvant chemotherapy and postoperative disease-free survival (DFS) of triple-negative breast cancer (TNBC) patients with axillary lymph node metastasis.Methods:A retrospective case series study was conducted. The data of 99 TNBC patients with axillary lymph node metastasis who underwent surgery after EC-T regimen (sequential docetaxel followed by epirubicin and cyclophosphamide) neoadjuvant chemotherapy at Suzhou Municipal Hospital and Xiangcheng People's Hospital from June 2016 to May 2022 were collected. All patients were required to collect peripheral blood samples within one week prior to puncture, and platelet, neutrophil and lymphocyte counts were analyzed using the blood analyzer. C-reactive protein level was analyzed using the fully automated biochemical analyzer, and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and immune inflammatory index (SII) were further calculated. Patients were divided into pathological complete remission (pCR) group and non-pCR group based on postoperative Miller Payne score, and the levels of various serum inflammation-related indicators before neoadjuvant chemotherapy were compared between the two groups; non-pCR patients were divided into high and low groups based on the median level of each indicator. Kaplan-Meier method was used to analyze the postoperative DFS status of each group. The impact of serum inflammatory-related indicators before neoadjuvant chemotherapy on postoperative DFS of patients was analyzed using Cox proportional hazards model for univariate and multivariate analyses.Results:The median age [ M ( Q1, Q3)] of 99 patients was 50 years old (39 years old, 64 years old); 47 cases were human epidermal growth factor receptor (HER2)-, 33 cases were HER2+, and 19 cases were HER2++ and fluorescence in situ hybridization-negative; there were 22 cases of pCR patients and 77 cases of non-pCR patients. Twenty-nine patients experienced recurrence or metastasis after surgery. The platelet count, PLR and SII of pCR group before neoadjuvant chemotherapy were lower than those of non-pCR group, and the differences were statistically significant (all P < 0.05). Among non-pCR patients, the DFS of high lymphocyte count before neoadjuvant chemotherapy group was better than that of low lymphocyte count group, while the DFS of high CRP, NLR, PLR, and SII groups was worse than that of low CRP, NLR, PLR, and SII groups, and the differences were statistically significant (all P < 0.05). Univariate analysis showed that lymphocyte count, NLR, PLR, CRP, and SII before neoadjuvant chemotherapy were all influencing factors for postoperative DFS in TNBC patients with axillary lymph node metastasis after neoadjuvant chemotherapy (all P < 0.05). Multivariate analysis showed that SII was an independent influencing factor for postoperative DFS in TNBC patients with axillary lymph node metastasis after neoadjuvant chemotherapy ( HR = 2.406, 95% CI: 1.147-5.617, P = 0.024). Conclusions:Serum inflammation-related indicators before neoadjuvant chemotherapy can serve as predictive factors for the efficacy of neoadjuvant chemotherapy and postoperative DFS in TNBC patients with axillary lymph node metastasis.

Objective:To explore the efficacy of ansa cervicalis anterior root-recurrent laryngeal nerve (RLN) anastomosis in the treatment of unilateral vocal fold paralysis (UVFP) and to analyze the effect of different pathogenic factors on efficacy.Methods:From January 2010 to January 2022, 428 patients (187 males and 241 females) at Changhai Hospital with UVFP who underwent ansa cervicalis anterior root-RLN anastomosis due to thyroid surgery, thoracic surgery, idiopathic vocal ford paralysis or high cranial base injury were analyzed. The course of nerve injury ranged from 6 to 24 months. Videostroboscopy, auditory perceptual evaluation parameters (GRBAS including Grade, Roughness, Breathiness, Asthenia, Strain), Voice Handicap Index (VHI-10), acoustic analysis including Jitter, Shimmer and noise to harmonic ratio (NHR), maximum phonation time (MPT) and laryngeal electromyography were used to evaluate the surgery efficacy, and the therapeutic difference of the above 4 different etiology patients receiving the operation was compared. Data processing was performed using SPSS 26.0 statistical software, and Wilcoxon signed rank test was used. Kruskal Wallis one-way ANOVA was used for those with equal variance.Results:At 12 months after operation, the affected vocal ford position, vocal ford edge, glottal closure, symmetry and regularity of vocal ford vibration were significantly improved in all four groups ( P<0.01). G, R, B, A, S, VHI-10, Jitter, Shimmer and NHR were significantly lower than those before operation, while, MPT was significantly longer ( P<0.01). Also, the maximum voluntary motor unit recruitment (VMUR) in the affected thyroarytenoid muscles and posterior cricoarytenoid muscles was significantly improved after surgery ( P<0.01). However, the results of thyroid surgery group, thoracic surgery group and idiopathic vocal ford paralysis group were better than those of high cranial base injury group respectively, and the differences were statistically significant ( P<0.05). Conclusion:Ansa cervicalis anterior root-RLN anastomosis has an obvious efficacy on the recovery of phonatory function in UVFP patients with different causes, but the high cranial base injury is significantly worse than that of vocal ford paralysis caused by other causes.

Objective:To explore the value of serum inflammation-related indicators in predicting the effect of neoadjuvant chemotherapy and postoperative disease-free survival (DFS) of triple-negative breast cancer (TNBC) patients with axillary lymph node metastasis.Methods:A retrospective case series study was conducted. The data of 99 TNBC patients with axillary lymph node metastasis who underwent surgery after EC-T regimen (sequential docetaxel followed by epirubicin and cyclophosphamide) neoadjuvant chemotherapy at Suzhou Municipal Hospital and Xiangcheng People's Hospital from June 2016 to May 2022 were collected. All patients were required to collect peripheral blood samples within one week prior to puncture, and platelet, neutrophil and lymphocyte counts were analyzed using the blood analyzer. C-reactive protein level was analyzed using the fully automated biochemical analyzer, and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and immune inflammatory index (SII) were further calculated. Patients were divided into pathological complete remission (pCR) group and non-pCR group based on postoperative Miller Payne score, and the levels of various serum inflammation-related indicators before neoadjuvant chemotherapy were compared between the two groups; non-pCR patients were divided into high and low groups based on the median level of each indicator. Kaplan-Meier method was used to analyze the postoperative DFS status of each group. The impact of serum inflammatory-related indicators before neoadjuvant chemotherapy on postoperative DFS of patients was analyzed using Cox proportional hazards model for univariate and multivariate analyses.Results:The median age [ M ( Q1, Q3)] of 99 patients was 50 years old (39 years old, 64 years old); 47 cases were human epidermal growth factor receptor (HER2)-, 33 cases were HER2+, and 19 cases were HER2++ and fluorescence in situ hybridization-negative; there were 22 cases of pCR patients and 77 cases of non-pCR patients. Twenty-nine patients experienced recurrence or metastasis after surgery. The platelet count, PLR and SII of pCR group before neoadjuvant chemotherapy were lower than those of non-pCR group, and the differences were statistically significant (all P < 0.05). Among non-pCR patients, the DFS of high lymphocyte count before neoadjuvant chemotherapy group was better than that of low lymphocyte count group, while the DFS of high CRP, NLR, PLR, and SII groups was worse than that of low CRP, NLR, PLR, and SII groups, and the differences were statistically significant (all P < 0.05). Univariate analysis showed that lymphocyte count, NLR, PLR, CRP, and SII before neoadjuvant chemotherapy were all influencing factors for postoperative DFS in TNBC patients with axillary lymph node metastasis after neoadjuvant chemotherapy (all P < 0.05). Multivariate analysis showed that SII was an independent influencing factor for postoperative DFS in TNBC patients with axillary lymph node metastasis after neoadjuvant chemotherapy ( HR = 2.406, 95% CI: 1.147-5.617, P = 0.024). Conclusions:Serum inflammation-related indicators before neoadjuvant chemotherapy can serve as predictive factors for the efficacy of neoadjuvant chemotherapy and postoperative DFS in TNBC patients with axillary lymph node metastasis.

Objective:To explore the efficacy of ansa cervicalis anterior root-recurrent laryngeal nerve (RLN) anastomosis in the treatment of unilateral vocal fold paralysis (UVFP) and to analyze the effect of different pathogenic factors on efficacy.Methods:From January 2010 to January 2022, 428 patients (187 males and 241 females) at Changhai Hospital with UVFP who underwent ansa cervicalis anterior root-RLN anastomosis due to thyroid surgery, thoracic surgery, idiopathic vocal ford paralysis or high cranial base injury were analyzed. The course of nerve injury ranged from 6 to 24 months. Videostroboscopy, auditory perceptual evaluation parameters (GRBAS including Grade, Roughness, Breathiness, Asthenia, Strain), Voice Handicap Index (VHI-10), acoustic analysis including Jitter, Shimmer and noise to harmonic ratio (NHR), maximum phonation time (MPT) and laryngeal electromyography were used to evaluate the surgery efficacy, and the therapeutic difference of the above 4 different etiology patients receiving the operation was compared. Data processing was performed using SPSS 26.0 statistical software, and Wilcoxon signed rank test was used. Kruskal Wallis one-way ANOVA was used for those with equal variance.Results:At 12 months after operation, the affected vocal ford position, vocal ford edge, glottal closure, symmetry and regularity of vocal ford vibration were significantly improved in all four groups ( P<0.01). G, R, B, A, S, VHI-10, Jitter, Shimmer and NHR were significantly lower than those before operation, while, MPT was significantly longer ( P<0.01). Also, the maximum voluntary motor unit recruitment (VMUR) in the affected thyroarytenoid muscles and posterior cricoarytenoid muscles was significantly improved after surgery ( P<0.01). However, the results of thyroid surgery group, thoracic surgery group and idiopathic vocal ford paralysis group were better than those of high cranial base injury group respectively, and the differences were statistically significant ( P<0.05). Conclusion:Ansa cervicalis anterior root-RLN anastomosis has an obvious efficacy on the recovery of phonatory function in UVFP patients with different causes, but the high cranial base injury is significantly worse than that of vocal ford paralysis caused by other causes.

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8⁺ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8⁺ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8⁺ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.