AIM:To explore the synergistic sensitization effect of human umbilical cord mesenchymal stem cell culture supernatant(hUMSC-CM)combined with temozolomide(TMZ)on various glioma cell lines,and to elucidate the underlying mechanisms.METHODS:The hUMSC-CM was harvested using two different serum deprivation tech-niques at 24 and 48 h,and was converted into freeze-dried powder,which was then given to rat malignant glioma cell line RG-2,human astrocytoma cell line U251 and human glioblastoma cell line LN-428 at 5 concentrations(0,1,3,6 and 9 g/L).The effectiveness and sensitivity of hUMSC-CM for inhibiting growth of glioma cells at 24,48 and 72 h were as-sessed using CCK-8 assay.Hematoxylin-eosin(HE)staining combined with CCK-8 assay was employed to evaluate the chemotherapy sensitivity of glioma cells after 48 h of treatment with TMZ at 6 concentrations(0,25,50,100,200 and 400 μmol/L).Two concentrations(3 and 9 g/L)of hUMSC-CM and 3 concentrations(50,100 and 200 μmol/L)of TMZ were chosen for concurrent treatment of glioma cells to assess the proliferation and pathological alterations.TUNEL staining was utilized to detect apoptosis.Flow cytometry was utilized to analyze cell cycle modifications.The expression alterations of apoptosis-inducing proteins,cleaved caspase-3,cleaved caspase-8 and cleaved PARP1,as well as autophagy-inducing proteins beclin-1 and LC3,were examined using Western blot to investigate the synergistic sensitization mechanism of hUMSC-CM combined with TMZ in vitro.RESULTS:The susceptibility of glioma cell lines to hUMSC-CM and TMZ varied,with RG-2 showing the highest sensitivity,followed by U251,and then LN-428.The inhibitory effect of hUMSC-CM(3 and 9 g/L)and TMZ(50,100 and 200 μmol/L)combined treatment on glioma cells was significantly greater than that that of single-agent treatments(P＜0.05),demonstrating a dose-and concentration-dependent enhancement.Notably,the combination of 9 g/L hUMSC-CM(C9)with 50 μmol/L TMZ(T50)effectively suppressed glioma cell growth.CCK-8 as-say indicated a significant reduction of cell viability in C9+T50 group compared with either C9 or T50 alone(P＜0.05).HE staining and TUNEL staining revealed pronounced morphological changes and significant apoptotic features in glioma cells treated with C9+T50.Flow cytometric analysis confirmed that C9+T50 induced cell cycle arrest in glioma cells.Fur-thermore,compared with control group,the levels of cleaved caspase-3,cleaved caspase-8,cleaved PARP1,beclin-1,and LC3-Ⅱ/LC3-Ⅰ were significantly elevated in the C9+T50-treated glioma cells(P＜0.01).CONCLUSION:(1)The concomitant administration of hUMSC-CM and TMZ exerts a broad inhibitory effect on glioma cells,with a synergistic sen-sitization observed across different cell lines.(2)The enhancement of glioma cell sensitivity to TMZ by hUMSC-CM may be attributed to the modulation of caspase-8/caspase-3/PARP1 signaling pathway and the induction of both apoptosis and autophagy in glioma cells.

Objective:To explore the clinical value of multidisciplinary team (MDT) treatment model for retroperitoneal soft tissue sarcoma (RPS) in the context of a regional medical center.Methods:The diagnosis and treatment of a patient with RPS in MDT model who were admitted to Xiamen Branch, Zhongshan Hospital, Fudan University in October 2020 were summarized, and the literature was reviewed.Results:The patient was a 59-year-old male, he was diagnosed with retroperitoneal INI-1-deficient poorly differentiated sarcoma with multiple systemic metastases. After several rounds of MDT discussions in Shanghai headquarter and Xiamen Branch of Zhongshan Hospital, Fudan University, the patient received systemic antitumor therapy combined with local therapy. After active treatment, the patient obtained a good curative effect. During the follow-up period, the liver and lung lesions slowly enlarged, and the treatment plan was adjusted. The patient had survived for more than 3 years.Conclusions:The diagnosis and treatment of RPS is complex, and the MDT model in the context of a regional medical center can help to formulate the optimal treatment plan for patients and may maximize the survival benefit of patients.

Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.

Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.

OBJECTIVE: To explore the pathological characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A) with cutaneous lichen amyloidosis (CLA). METHODS: Clinical data of 51 members from 7 unrelated pedigrees of MEN2A-CLA were collected. Systemic clinical investigations including biochemical testing, imaging examination, germline RET variant screening and histopathological examination were carried out. RESULTS: RET gene variants were detected in 28 patients with MEN2A (C634G/F/R/S/W and C611Y) including 12 males and 16 females, with the mean age of diagnosis being (41.1 ± 18.3) years old, which were consistent with their clinical manifestations. The incidence of medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), hyperparathyroidism (HPTH) and CLA among 28 MEN2A patients were 89.3%, 28.6%, 7.1% and 28.6%, respectively. Comparison of the incidence of MTC/PHEO/HPTH and CLA between C611Y and C634G/F/R/S/W, only PHEO and CLA in C611Y were lower than those in C634G/F/R/S/W (P < 0.05; P < 0.05). Among 8 patients with CLA, the male to female ratio was 2 : 6. The clinical features included pruritus in the interscapular region and presence of dry, thickened, scaly, brown pigment, clustered or desquamate-like plaques. The mean onset age of CLA [(18.4 ± 4.6) years] versus the mean age at diagnosis of CLA or MEN2A were significantly different (P < 0.001; P < 0.001). CONCLUSION MEN2A-CLA may be the early clinical manifestation of MEN2A and most frequently occurred along with RET-C634 variant. To facilitate the recognition of MEN2A-CLA, to combine family investigation and screening of RET variant are helpful for early diagnosis and standardized treatment, which can improve the long-term outcome of MEN2A-specific tumors.
Adolescent ; Adrenal Gland Neoplasms ; Adult ; Amyloidosis, Familial ; Carcinoma, Neuroendocrine ; China ; Female ; Humans ; Lichens ; Male ; Middle Aged ; Multiple Endocrine Neoplasia Type 2a/genetics* ; Pheochromocytoma ; Proto-Oncogene Proteins c-ret/genetics* ; Skin Diseases, Genetic ; Thyroid Neoplasms/genetics* ; Young Adult

Objective To detect the radiation of ¹³¹I in treatment site of a grade A tertiary hospital. Methods A total of 25 patients with thyroid cancer were administrated ¹³¹I at a total dose of 82880 MBq. After administration, the ambient dose equivalent rate of the ward was detected with X- and γ-ray detectors. After patient discharge, surface contamination of the ward was detected with α/β surface contamination meter. During patient hospitalization and on the day of discharge, air samples were collected from ¹³¹I treatment site and office area. The air samples were measured using a HPGe γ-ray spectrometer and the concentration of ¹³¹I in air was calculated. Results The ambient dose equivalent rate in the ward ranged from 0.15 to 0.46 μSv/h. Before ward cleaning, surface contamination ranged from 0.53 to 40.1 Bq/cm² and the highest value was recorded on the toilet. Within 4 h after administration, the concentrations of ¹³¹I in air in treatment site and the corridor of the office area were 1.74 Bq/m³ and 0.66 Bq/m³, respectively. The ventilation air flow rate in the treatment site was 0.50 m/s. Ventilation decreased the concentration of ¹³¹I in air by 29.7%, 79.7%, and 53.3% compared with the previous day during hospitalization and on the day of discharge. Conclusion The radiation of external exposure of ¹³¹I in the treatment site is low and the shielding is effective. Before ward cleaning, the surface contamination is lower than the required limits except for the toilet. Ventilation is the primary way to reduce the concentration of ¹³¹I in air.

Objective:To evaluate the efficacy and safety of bendamustine monotherapy in Chinese patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) .Methods:This prospective, multicenter, open label, single-arm, phase Ⅱ study investigated bendamustine’s efficacy and safety in Chinese patients with R/R B-NHL. A total of 78 patients with B-NHL in 11 hospitals in China from March 2012 to December 2016 were included, and their clinical characteristics, efficacy, and survival were analyzed.Results:The median age of all patients was 58 (range, 24-76) years old, and 69 (88.4% ) patients had stage Ⅲ/Ⅳ disease. 61 (78.2% ) patients were refractory to previous treatments. Patients received a median of 4 (range, 1-10) cycles of bendamustine treatment. The overall response rate was 61.5 (95% CI 49.8-72.3) % , the median response duration was 8.3 (95% CI 5.5-14.0) months, and the complete remission (CR) rate was 5.1 (95% CI 1.4-12.6) % . In the full analysis set, median progression-free survival (PFS) and median OS were 8.7 (95% CI 6.7-13.2) months and 25.5 months (95% CI 14.2 months to not reached) , respectively, after a median follow-up of 33.6 (95% CI 17.4-38.8) months. Lymphopenia (74.4% ) , neutropenia (52.6% ) , and leukopenia (39.7% ) , thrombocytopenia (29.5% ) and anemia (15.4% ) were the most common grade 3-4 hematologic adverse events (AE) . The most frequent non-hematologic AEs included nausea (43.6% ) , vomiting (33.3% ) , and anorexia (29.5% ) . Univariate and multivariate analysis showed that <4 cycles of bendamustine treatment was a poor prognostic factor for PFS ( P=0.003) , and failure to accept fludarabine containing regimen was a poor prognostic factor for OS ( P=0.009) . Conclusion:Bendamustine monotherapy has good efficacy and safety in the treatment of patient with R/R B-NHL.

Objective:To study the variation in activity in patient′s body with differentiated thyroid cancer (DTC) treated with 131I and external dose level, analyze the relationship between the both, and estimate the correction factor for the dose equivalent rate for the patients with residual activity of 400 MBq. Methods:A total of 43 DTC patients who received 131I therapy for the first time after total thyroidectomy were studied. The dose was 1 850-3 700 MBq and average dose was (2 405±777) MBq. The measurements of residual activity in patient′s body and of dose equivalent rate at 0.3, 1 and 3 m in front of the patients were performed at 2, 6, 20, 22, 24, 27, 30, 44, 46, 48, 54, 68 and 72 h after administration of 131I. Results:The residual activity in patient′s body after 131I therapy varied with time as a function of A= A0 (1.033 16e -0.062 4t+ 0.017 17). It can be estimated that the effective half-life of DTC patients treated with thyroid remnant 131I ablation therapy is 12.19 h. It needs only 26.4-38.9 h to reduce the internal activity to the 400 MBq. The functions of variation with time of normalized dose equivalent rate at 0.3, 1, and 3 m away from patients were: H· 0.3=127.220 7e -0.054 8t+ 3.765 71; H· 1=30.225 8e -0.064 4t+ 0.824 67; and H· 3=4.161 9e -0.061 5t+ 0.167 97, respectively. There was a positive correlation between residual activity and dose equivalent rate at 1 m ( r=0.982, P<0.05), and the function is H· 1=0.025 A+ 1.245. When residual activities in DTC patient′s body were 1 000, 700 and 400 MBq, the corresponding dose equivalent rates at 1 m from patients were 26.2, 18.7 and 11.2 μSv/h, respectively. The correction factors for dose equivalent rate at 0.3, 1 and 3 m from patients with 400 MBq were 0.25, 0.49 and 0.70, respectively. Conclusions:DTC patients with administration of 131I activity below 3 700 MBq need only to be hospitalized for two days to reach the discharge standards. When the residual activity in DTC patient′s body drops to 400 MBq, the dose equivalent rate at 1 m is far less than 25 μSv/h. Simply using the point source formula to estimate the dose equivalent rate around the patient will result in overestimation. Therefore, the correction factor used in the estimation of radiation doses to patients by using the formula needs to be further studied so as to make the model-based estimated result more consistent with the actual situation.

Objective:To explore the expression of Fbxw7 protein and its clinical significance in diffuse large B-cell lymphoma (DLBCL), and to provide a basis for prognostic judgement and searching the new therapeutic targets of DLBCL.Methods:A total of 72 patients with newly diagnosed DLBCL who received immunohistochemical detection of c-myc protein from January 2011 to September 2017 in Cancer Hospital Affilicoted to Zhengzhou University were enrolled. The paraffin-embedded specimens after lymph node biopsy and the clinical data of patients were also collected. At the same time, 22 samples of lymph node reactive hyperplasia were selected as the control group. Immunohistochemical method was used to detect the expression of Fbxw7 protein in DLBCL tissues and control tissues. The relationship between the expression of Fbxw7 protein and c-myc protein, the association of Fbxw7 protein expression with DLBCL patients' clinicopathological characteristics, efficacy and prognosis were analyzed.Results:The positive rate of Fbxw7 protein in DLBCL tissues was lower than that in control tissues, and the difference was statistically significant [63.89% (46/72) vs. 86.36% (19/22), χ 2 = 3.990, P = 0.046]. Among DLBCL patients, the positive rate of Fbxw7 protein in non-germinal center B cell (non-GCB) group was lower than that in germinal center B cell (GCB) group, and the difference was statistically significant [48.15% (13/27) vs. 73.33% (33/45), χ 2 = 4.639, P = 0.031]. There were no statistically significant differences in the positive rate of Fbxw7 protein among patients with different age, gender, neoplasm staging, international prognostic index (IPI) scores, B symptom, Eastern Cooperative Oncology Group (ECOG) score, lactate dehydrogenase (LDH) level, β 2 microglobulin level, and therapeutic efficacy after initial treatment (all P > 0.05). In DLBCL tissues, the expression of Fbxw7 and c-myc protein was negatively correlated ( r = -0.255, P = 0.031). The 3-year overall survival (OS) rate and 3-year progression-free survival (PFS) rate (88.3% and 82.0%) of the Fbxw7 positive group were higher than those of the Fbxw7 negative group (70.2% and 60.1%). Cox multivariate analysis showed that the down-regulation of Fbxw7 protein expression was an independent risk factor affecting OS and PFS in DLBCL patients ( HR = 3.656, 95% CI 1.055-12.674, P = 0.041; HR = 2.897, 95% CI 1.092-7.688, P = 0.033). Conclusions:The expression of Fbxw7 protein and c-myc protein in DLBCL patients is negatively correlated. Fbxw7 protein is down-regulated in DLBCL, and it is more obvious in non-GCB subtype. The down-regulated expression of Fbxw7 protein is related to the poor prognosis of DLBCL, and Fbxw7 may become a new therapeutic target of DLBCL.

Objective:To evaluate the clinical effect of the treatment of scar formation after severe acne type Ⅳ by acupuncture.Methods:In Henan Traditional Chinese Medicine Hospital, 60 patients with acne who met the inclusion criteria were selected and divided into observation group and control group according to the randomized controlled grouping method. The observation group(9 male and 21 female, age 18-29) was treated with fire needle and salicylic acid.The control group(10 male and 20 female, age 18-27 ) was treated with needle and salicylic acid.The patients in both groups were treated with tanshinone capsule and salicylate acne pill orally.The course of treatment was 8 weeks. The two groups of clinical efficacy, acne severity score scale (Gags) to evaluate symptom improvement, vancouver scar scale, acne scar weight score were observed and compared.Results:Eight weeks after treatment, the effect rate was 90.00% (27/30) in the observation group and 68.97% (20/29) in the control group. The scores of Vancouver scar scale were (3.66 ± 0.91) in the observation group and (5.06 ± 1.09) in the control group ( P< 0.01). The scores of acne scar weight score were (39.40 ± 16.90) in the observation group and (53.16 ± 17.19) in the control group( P< 0.01). The scores of Gags in the observation group and the control group were (10.31 ± 2.14) and (17.55 ± 2.63)( P< 0.01), respectively. Conclusions:The treatment of Ⅳ grade severe acne skin lesions by fire needle is safe, effective, reliable and easy to operate. It can safely and effectively improve the patient’s facial skin lesions, and reduce the possibility of scar formation and pigmentation, so it is worthy of clinical application.