Objective:To investigate the relationship between the radioresistance of anaplastic thyroid cancer (ATC) and the induction of epithelial-mesenchymal transition (EMT).Methods:Firstly, the radiotherapy sensitivity of differentiated thyroid cancer cells (TPC-1, FTC-133) and ATC cells (CAL-62, 8305C), and the protein levels of E-cadherin, N-cadherin and vimentin proteins after 6 Gy irradiation were detected. The changes in transcriptional levels before and after 4 Gy X-ray radiation of ATC cells were analyzed using mRNA sequencing. Then, the ATC radio-resistant cell models were constructed and validated, and the cell line with the highest radio-resistance was selected for subsequent experiments. Radio-resistant cells were classified into the control group (no treatment), EMT-inhibitor group (EMT-inhibitor-1 pre-treatment), Vactosertib group [transforming growth factor-β(TGF-β) inhibitor Vactosertib pre-treatment), and si-Snail group (knockdown of Snail gene by siRNA transfection), respectively. The expression level of EMT related proteins and TGF-β/Smad signaling pathway related proteins, the cloning efficiency, and the phosphorylated-histone H2A family member X (γH2AX) positive cells rate in the treatment groups and the control group were detected by Western blotting, clone formation assay, immunofluorescence, respectively, reflecting the changes in EMT level and DNA repair ability. Comparison between two groups was performed by Dunnett t-test. Comparison among multiple groups was conducted by one-way ANOVA. Results:The radiosensitivity of ATC cells were lower than that of differentiated thyroid cancer cells. After irradiation, the expression level of E-cadherin was low, those of N-cadherin and vimentin were high, EMT level was increased, and the expression levels of TGF-β/Smad signaling pathway-associated proteins were up-regulated in ATC cells. After use of EMT inhibitor, Vactosertib and Snail knockdown, the expression levels of EMT-associated proteins were down-regulated, cell survival fraction was declined, γH2AX positive cell rate was increased, DNA damage repair ability was weakened and the radiosensitivity was enhanced in radiotherapy-resistant ATC strains. Conclusions:The level of radiotherapy resistance in ATC cells is positively correlated with the EMT level, and the mechanism of radiotherapy resistance is related to the activation of the TGF-β/Smad/Snail pathway after irradiation.

Myelodysplastic syndrome (MDS) is a heterogeneous clonal myeloid malignancy with a variable prognosis. Some myeloid-related gene alterations have been found to be associated with the diagnosis and prognosis of MDS. As a result, multiple myeloid-related gene mutations have been added to International Working Group for Prognosis in MDS (IWG-PM) and other MDS prognosis evaluation systems as diagnostic and prognostic indications. Further research using the variable allele frequency (VAF) detection technique demonstrated that myeloid-related genes evolve dynamically during the course of MDS with some regularity. Furthermore, significant relevance have been found between the VAF evolution of particular myeloid-related genes and MDS subtypes, risk classification, and prognosis. This article provides an overview of the application of VAF of myeloid-related gene mutations in MDS research, highlighting the critical role of gene mutation VAF in MDS subtype categorization, risk stratification, and therapy response assessment.

Myelodysplastic syndrome (MDS) is a heterogeneous clonal myeloid malignancy with a variable prognosis. Some myeloid-related gene alterations have been found to be associated with the diagnosis and prognosis of MDS. As a result, multiple myeloid-related gene mutations have been added to International Working Group for Prognosis in MDS (IWG-PM) and other MDS prognosis evaluation systems as diagnostic and prognostic indications. Further research using the variable allele frequency (VAF) detection technique demonstrated that myeloid-related genes evolve dynamically during the course of MDS with some regularity. Furthermore, significant relevance have been found between the VAF evolution of particular myeloid-related genes and MDS subtypes, risk classification, and prognosis. This article provides an overview of the application of VAF of myeloid-related gene mutations in MDS research, highlighting the critical role of gene mutation VAF in MDS subtype categorization, risk stratification, and therapy response assessment.

Objective:To investigate the relationship between the radioresistance of anaplastic thyroid cancer (ATC) and the induction of epithelial-mesenchymal transition (EMT).Methods:Firstly, the radiotherapy sensitivity of differentiated thyroid cancer cells (TPC-1, FTC-133) and ATC cells (CAL-62, 8305C), and the protein levels of E-cadherin, N-cadherin and vimentin proteins after 6 Gy irradiation were detected. The changes in transcriptional levels before and after 4 Gy X-ray radiation of ATC cells were analyzed using mRNA sequencing. Then, the ATC radio-resistant cell models were constructed and validated, and the cell line with the highest radio-resistance was selected for subsequent experiments. Radio-resistant cells were classified into the control group (no treatment), EMT-inhibitor group (EMT-inhibitor-1 pre-treatment), Vactosertib group [transforming growth factor-β(TGF-β) inhibitor Vactosertib pre-treatment), and si-Snail group (knockdown of Snail gene by siRNA transfection), respectively. The expression level of EMT related proteins and TGF-β/Smad signaling pathway related proteins, the cloning efficiency, and the phosphorylated-histone H2A family member X (γH2AX) positive cells rate in the treatment groups and the control group were detected by Western blotting, clone formation assay, immunofluorescence, respectively, reflecting the changes in EMT level and DNA repair ability. Comparison between two groups was performed by Dunnett t-test. Comparison among multiple groups was conducted by one-way ANOVA. Results:The radiosensitivity of ATC cells were lower than that of differentiated thyroid cancer cells. After irradiation, the expression level of E-cadherin was low, those of N-cadherin and vimentin were high, EMT level was increased, and the expression levels of TGF-β/Smad signaling pathway-associated proteins were up-regulated in ATC cells. After use of EMT inhibitor, Vactosertib and Snail knockdown, the expression levels of EMT-associated proteins were down-regulated, cell survival fraction was declined, γH2AX positive cell rate was increased, DNA damage repair ability was weakened and the radiosensitivity was enhanced in radiotherapy-resistant ATC strains. Conclusions:The level of radiotherapy resistance in ATC cells is positively correlated with the EMT level, and the mechanism of radiotherapy resistance is related to the activation of the TGF-β/Smad/Snail pathway after irradiation.

Objective:To analyze the short- and medium-term efficacy, factors influencing the efficacy, and safety of dupilumab alone or in combination for the treatment of bullous pemphigoid (BP) .Methods:A single-center retrospective cohort study was conducted. Clinical data were collected from adult BP patients, who were regularly followed up and treated with dupilumab at the Department of Dermatology, Peking University First Hospital between March 2021 and June 2022. Dupilumab was administered subcutaneously every 2 weeks at a dose of 300 mg (except for the initial dose being 600 mg). Previous medications included glucocorticoids, minocycline, immunosuppressants, etc., and their dose remained unchanged or decreased according to patient condition. The short- and medium-term response rates were evaluated at weeks 2 and 16 after the first injection of dupilumab, respectively. Multivariate logistic regression analysis was conducted to identify factors influencing the disease control rate at week 2, and odds ratios ( ORs) were calculated; a multivariate Cox regression model was employed to analyze factors influencing the disease control rate within 16 weeks of follow-up, and hazard ratios ( HRs) were calculated; multiple linear regression analysis was performed to determine factors associated with the time to pruritus relief. Results:A total of 104 BP patients were eligible, including 60 males and 44 females; they were aged 75.6 ± 12.8 years, and the disease duration ( M [ Q1, Q3]) was 4.0 (2.0, 17.0) months. According to the percentage of the lesion area to the total body surface area, the disease severity was graded, and there were 17 mild cases, 30 moderate cases, 31 severe cases, and 26 extremely severe cases; 56 patients (53.9%) were treated with dupilumab combined with oral glucocorticoids at doses of 20.0 (15.0, 30.0) mg/d. At week 2 after the start of treatment, 63 patients (60.6%) achieved disease control, and 37 (35.6%) achieved marked disease control, resulting in a short-term response rate of 96.2%. Fifty-five patients were followed up for 16 weeks, 54 (98.2%) achieved improvement, and the systemic glucocorticoid dose was reduced to 10.0 (10.0, 17.5) mg/d. Disease control was achieved in 92 of 104 patients (88.5%) within 16 weeks, with the time to disease control being 14.0 (13.0, 26.0) days and the time to pruritus relief being 12.0 (3.0, 14.0) days. Multivariate logistic regression analysis showed that the higher the baseline disease severity, the lower the disease control rate at week 2 (compared with extremely severe cases, mild cases: OR = 37.655, 95% CI: 3.664, 386.981; moderate cases: OR = 12.143, 95% CI: 2.609, 56.528; severe cases: OR = 4.014, 95% CI: 1.121, 14.369, all P < 0.05). Multivariate Cox regression analysis showed that compared with severe BP patients, mild ( HR = 2.478, 95% CI: 1.200, 5.114, P = 0.014) and moderate BP patients ( HR = 2.076, 95% CI: 1.067, 4.038, P = 0.031) were more likely to achieve disease control during the 16-week treatment and follow-up. Multiple linear regression analysis revealed that the disease duration significantly influenced the time to pruritus relief ( P = 0.006), and the longer the disease duration, the longer the time to pruritus relief. During the follow-up, 13 adverse events occurred in 11 patients (10.6%), including 6 with pulmonary infections, 2 with heart failures, 1 with scabies, 1 with viral conjunctivitis, 1 with pericardial effusion (with a high likelihood of idiopathic pericarditis), 1 with organ failure, and 1 with intracerebral hemorrhage, but none of them were clearly related to dupilumab and most of them did not affect the treatment continuation; 3 deaths were reported, including 2 due to organ failures and 1 due to lung infection, which were all unrelated to dupilumab as determined by specialists. Conclusion:Dupilumab combination therapy for BP could result in rapid disease control, relieve pruritus, and reduce systemic glucocorticoid dosage, with a good safety profile.

OBJECTIVE: To compare the effectiveness of robot-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open freehand TLIF for the treatment of single-level degenerative lumbar spondylolisthesis (DSL) and analyse the influence on postoperative adjacent segmental degeneration (ASD). METHODS: The clinical data of 116 patients with L _4、5 DLS who were admitted between November 2019 and October 2021 and met the selection criteria were retrospectively analyzed. According to the surgical methods, they were divided into the robotic group (45 cases, who underwent robot-assisted MIS-TLIF) and the open group (71 cases, who underwent open freehand TLIF). There was no significant difference in baseline data such as gender, age, body mass index, DLS Meyerding grading, and preoperative Pfirrmann grading, Weishaupt grading, L _{3, 4} intervertebral disc height (DH), L _{3, 4} intervertebral mobility, sagittal parameters [including pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT)], and Cage height ( P>0.05). The grade of facet joint violation (FJV) by pedicle screws on the superior articular process was assessed postoperatively. Sagittal parameters, L _{3, 4} DH, L _{3, 4} DH loss, and L _{3, 4} intervertebral mobility were measured preoperatively and at last follow-up in order to determine whether ASD occurred. Based on the occurrence of postoperative ASD, logistic regression analysis was used to identify the risk factors for ASD after TLIF. RESULTS: Patients in both groups were followed up 21-47 months, with a mean of 36.1 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The occurrence of postoperative FJV was significantly better in the robotic group than in the open group ( P<0.05). At last follow-up, the difference in the change values of sagittal parameters PI, PT, SS, and LL was not significant when comparing the two groups of patients ( P>0.05); the change values of L _{3, 4} DH and L _{3, 4} DH loss in the robotic group were smaller than those in the open group, and the change value of L _{3, 4} intervertebral mobility was larger than that in the open group, and the differences were significant ( P<0.05). At last follow-up, ASD occurred in 8 patients (17.8%) in the robotic group and 35 patients (49.3%) in the open group, and the difference in ASD incidence between the two groups was significant ( P<0.05). logistic regression analysis showed that open surgery, preoperative Pfirrmann grading Ⅳ-Ⅴ, preoperative Weishaupt grading ≥2, and postoperative FJV grading ≥1 were risk factors for the development of ASD after TLIF ( P<0.05). CONCLUSION Compared with traditional open surgery, orthopedic robot-assisted MIS-TLIF in the treatment of single-level DLS can more accurately insert pedicle screws, reduce the loss of DH and the occurrence of FJV, and effectively reduce the incidence of mid-postoperative ASD. Preoperative disc and synovial joint degeneration in adjacent segments, nonrobotic-assisted minimally invasive therapy, and FJV are risk factors for ASD after TLIF.
Humans ; Spinal Fusion/methods* ; Spondylolisthesis/surgery* ; Lumbar Vertebrae/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Robotic Surgical Procedures/methods* ; Male ; Treatment Outcome ; Female ; Intervertebral Disc Degeneration/surgery* ; Retrospective Studies ; Postoperative Complications/etiology* ; Risk Factors ; Middle Aged

Objective:To retrospectively analyze the efficacy and safety of dupilumab in the treatment of bullous pemphigoid (BP) .Methods:Clinical data were collected from BP patients who received injections of dupilumab at an initial dose of 600 mg followed by an every-2-week regimen at a dose of 300 mg (the frequency of injections could be increased if necessary) in Department of Dermatology, Peking University First Hospital from October 2020 to October 2021, and their clinical manifestations and changes in laboratory indices were analyzed.Results:A total of 21 BP patients treated with dupilumab were included in this study. Nineteen (90.5%) patients achieved complete or marked disease control after 2-week treatment with dupilumab; 12 patients were followed up for 16 weeks, and all maintained complete disease control at 16 weeks. All patients had a bullous pemphigoid disease area index (BPDAI) score of 122.5 ± 51.1 points at baseline, which decreased to 30.6 ± 27.4 points after 2-week treatment with dupilumab ( t = 8.53, P < 0.001) , and continued to decrease to 12.7 ± 9.1 points after 4-week treatment ( t = 9.73, P < 0.001) . Pruritus was markedly relieved in all the 21 patients within 4-week treatment with dupilumab. Among 10 patients with elevated eosinophil counts at baseline, the eosinophil counts markedly decreased in 9 after treatment. The serum IgE level was elevated in 7 patients at baseline, which markedly decreased in 6 after treatment. Viral conjunctivitis occurred in 1 (4.8%) patient, and no adverse reactions were observed in other patients. Conclusion:Dupilumab is effective in the control of BP and relief of pruritus, with a favorable safety profile.

ObjectiveTo observe the clinical efficacy of electroacupuncture at Baihuanshu (BL30) and Huiyang (BL35) in treating chronic abacterial prostatitis.MethodSixty patients with chronic abacterial prostatitis were divided into a treatment group(n=30) and a control group (n=30), respectively to receive electroacupuncture plus Chinese herbal medicine and Chinese herbal medicine alone.ResultAfter intervention, the scores of National Institutes of Health-Chronic Prostatitis symptom index (NIH-CPS) dropped in both treatment and control groups, while the decrease was more significant in the treatment group (P<0.05); the pain or discomfort score from the NIH-CPS dropped in both groups, while the decrease was more marked in the treatment group (P<0.05).ConclusionElectroacupuncture and Chinese herbal medicine both are effective in treating chronic abacterial prostatitis, and electroacupuncture plus Chinese herbal medicine can produce a more significant efficacy than Chinese herbal medicine alone.