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.

AIM:To investigate the oncolytic effect of human umbilical cord mesenchymal stem cells(hUMSCs)delivering reovirus type 3(Reo3)on chronic myeloid leukemia(CML)K562 cells.METHODS:The expression of junc-tional adhesion molecule-A(JAM-A),a receptor susceptible to Reo3,on the surface of hUMSCs and K562 cells was as-sessed by flow cytometry.Intracellular viral inclusion body distribution 72 h after Reo3 infection in hUMSCs was observed by electron microscopy.The hUMSCs were infected with various multiplicities of infection(MOI)of Reo3(MOI=0,1,2 and 3)for 24,48,72,96 and 120 h,and the most suitable MOI was identified by CCK-8 assay.Subsequently,hUMSCs were infected with the optimal titer of Reo3 for the same durations,and supernatants were collected.The titer of Reo3 in the supernatant from each group was measured using mouse fibroblast L929 cells combined with median tissue culture in-fectious dose(TCID50)method,determining the optimal infection time.The K562 cells were divided into 4 groups:con-trol group,hUMSCs group,Reo3 group,and hUMSCs-Reo3 group.Ratios of hUMSCs to K562 cells in hUMSCs group and hUMSCs-Reo3 group were set at low,medium and high(5∶1,10∶1 and 20∶1).The changes of K562 cell viability af-ter co-cultured with hUMSCs-Reo3 for 24,48 and 72 h were analyzed by CCK-8 assay.The apoptosis of K562 cells was evaluated by flow cytometry.The half maximal effective concentration(EC50)of anti-Reo3 monoclonal antibody was deter-mined using L929 cells.The oncolytic effect of hUMSCs-Reo3 on K562 cells with antibody present in vitro was verified.Western blot analysis was used to detect the protein levels of Bcl-2,Bax,survivin and cleaved caspase-3 in K562 cells af-ter treatment.A BALB/c nude mouse subcutaneous tumor model was constructed with K562 cells(n=6)to analyze the in vivo anti-tumor effect of hUMSCs-Reo3.RESULTS:The expression levels of JAM-A on the surfaces of hUMSCs and K562 cells were found to be 11.0%and 99.0%,respectively.Electron microscopy revealed a significant presence of viral inclusion bodies within hUMSCs 72 h following infection with Reo3.Within 120 h,no statistically significant difference was observed in the viability of hUMSCs between Reo3(MOI=1)group and uninfected group,establishing the optimal MOI.The TCID50 results indicated that the highest virus titer in the lysate of hUMSCs in Reo3(MOI=1)group occurred 48 h after infection,determining 48 h as the optimal infection time.The K562 cells co-cultured with hUMSCs-Reo3 for 24,48 and 72 h showed a dose-and time-dependent inhibition of cell viability.The EC50 of the anti-Reo3 monoclonal antibody was found to be 1∶34.Even in the presence of antibodies at various concentrations(1∶34,1∶300 and 1∶600),hUMSCs were capable of transporting Reo3 to inhibit K562 cell viability and induce apoptosis in vitro.Compared with control group,significant down-regulation of Bcl-2 and survivin expression levels in K562 cells was noted after 48 h of co-culture with hUMSCs-Reo3(P<0.05),while Bax and cleaved caspase-3 expression levels were significantly up-regulated(P<0.05 or P<0.01).In the BALB/c nude mouse tumor-bearing model,determination of tumor volume changes,pathological examination of tumor tissue and major organs,and assessment of cathepsin B/L activity using a small animal live imaging system confirmed the oncolytic effect of hUMSCs-Reo3 on K562 cells in vivo without adverse effects on normal tissues.CONCLUSION:The hUMSCs are effective in transporting Reo3,and this delivery system is capable of releasing suffi-cient quantities of Reo3 in both in vivo and in vitro settings to inhibit the malignant proliferation of K562 cells and promote apoptosis,thereby exerting an oncolytic effect.

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 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 characterize the humeral head necrosis after open reduction and anatomic locking plate fixation of complex proximal humeral fractures.Methods:A retrospective study was conducted of the 20 patients who had been treated for humeral head necrosis after surgery of complex proximal humeral fracture at Department of Traumatic Orthopaedics, Beijing Jishuitan Hospital from September 2012 to June 2020. They were 7 males and 13 females with an average age of 57.4 years (from 35 to 84 years). Analyzed were their fracture types, time for diagnosis of humeral head necrosis, length of the medial residual bone, thickness of the humeral head and shoulder function.Results:The 20 patients were followed up for 8 to 104 months (average, 48.3 months). According to the Neer classification, there were 8 three-part fractures and 12 four-part fractures; shoulder dislocation was complicated in 10 cases. According to the AO-OTA classification, there were 16 type C fractures and 4 type B fractures. The length of the medial residual bone averaged 4.8 mm (from 0 to 10.7 mm); the medial soft tissue hinge was damaged in 18 cases and the thickness of the humeral head averaged 20.6 mm (from 13.6 to 33.0 mm). All fractures got united at the first stage after an average time of 8.4 weeks (from 5 to 12 weeks). The time for diagnosis of humeral head necrosis averaged 16.5 months (from 8 to 24 months). At the final follow-up, the Constant-Murley score of the affected side averaged 53.4 (from 22 to 74) while that of the healthy side 85.5 (from 53 to 98), with a ratio of affected side to healthy side of 62.43% (from 27.95 to 82.70%).Conclusions:Necrosis of the humeral head was common after surgery for complex proximal humerus fractures, most of which were three- or four-part ones or combined with shoulder dislocation. In most of the patients, the medial soft tissue hinge was damaged and the length of the residual medial bone usually shorter than 8 mm. Necrosis of the humeral head happened late after surgery. The function of the affected shoulder was significantly lower than that of the healthy side.

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 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 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.

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.