Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*

Concerns has been raised in improving the quality of adaptive design randomized trials reports. Based on the CONSORT 2010 (Consolidated Standards of Reporting Trials), The Adaptive designs CONSORT Extension (ACE) has developed items and reporting specifications for adaptive design trials. This paper presents a brief explanation of the extension and new items of ACE and introduces the applications of ACE checklist with examples.
Checklist ; Humans ; Randomized Controlled Trials as Topic ; Research Design ; Research Report

OBJECTIVE: To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS: In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS: Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Moxibustion ; Osteoarthritis, Knee/therapy* ; Treatment Outcome

OBJECTIVE: To compare the clinical efficacy of lengthened proximal femoral nail anti-rotation(PFNA) combined with minimally invasive percutaneous plate osteosynthesis(MIPPO) and common PFNA in the treatment of AO-A3.3 intertrochanteric fracture. METHODS: The clinical data of 58 patients with AO-A3.3 intertrochanteric fracture treated from January 2015 to April 2020 were retrospectively analyzed. Among them, 27 patients were treated with extended PFNA + MIPPO plate to reconstruct the lateral wall (group A), and 31 patients were treated with closed reduction and PFNA fixation (group B). The bleeding volume, operation time, femoral neck length and tip apex distance(TAD), fracture healing time and postoperative complications were observed and compared between two groups. Harris score was used to evaluate hip joint function 10 months after operation. RESULTS: All patients were followed up for 12 to 28 months. The incision healed well after operation. The bleeding volume and operation time of group A were significantly more than that of group B (P<0.05), and the fracture healing time of group A was significantly less than that of group B(P<0.05). There was no significant difference in the length of femoral neck between two groups at 2 days after operation(P>0.05). The length of femoral neck at 6 months after operation in each group was shorter than that at 2 days after operation(P<0.05), and the shortening of femoral neck at 6 months after operation in group B was significantly shorter than that in group A(P<0.05). There was no significant difference in TAD values between two groups at the same time point(P>0.05) at 2 days and 6 months after operation. There was no significant difference in TAD values between 2 days and 6 months after operation(P>0.05). The incidence of complications in group B was significantly higher than that in group A(P<0.05). The Harris scores of hip joint function in group A were higher than those in group B 10 months after operation (P<0.05). CONCLUSION Compared with the treatment of AO-A3 femoral intertrochanteric fracture with closed reduction and PFNA fixation, the lengthened PFNA combined with MIPPO small plate for reconstruction and fixation of the lateral wall can promote the fracture healing, improve the patient's functional recovery, and significantly reduce the complications.
Humans ; Bone Nails ; Fracture Fixation, Intramedullary ; Retrospective Studies ; Hip Fractures/surgery* ; Bone Plates ; Femoral Fractures/surgery*

Caffeic acid and its oligomers are the main water-soluble active constituents of the traditional Chinese medicine(TCM) Arnebiae Radix. These compounds possess multiple biological activities such as antimicrobial, antioxidant, cardiovascular protective, liver protective, anti-liver fibrosis, antiviral and anticancer activities. The phenylpropanoid pathway in plants is responsible for the biosynthesis of caffeic acid and its oligomers. Glycosylation can change phenylpropanoid solubility, stability and toxic potential, as well as influencing compartmentalization and biological activity. In view of the important role played by de-glycosylation in the regulation of phenylpropanoid homeostasis, the biosynthesis of caffeic acid and its oligomers are supposed to be under the control of relative UDP-glycosyltransferases(UGTs). Through the data mining of Arnebia euchroma transcriptome, we cloned 15 full-length putative UGT genes. After recombinant expression using the prokaryotic system, the crude enzyme solution of the putative UGTs was examined for the glycosylation activities towards caffeic acid and rosmarinic acid in vitro. AeUGT_01, AeUGT_02, AeUGT_03, AeUGT_04 and AeUGT_10 were able to glycosylate caffeic acid and/or rosmarinic acid resulting in different mono-and/or di-glycosylated products in the UPLC-MS analyses. The characterized UGTs were distantly related to each other and divided into different clades of the phylogenetic tree. Based on the observation that each characterized UGT exhibited substrate or catalytic similarity with the members in their own clade, we supposed the glycosylation abilities towards caffeic acid and/or rosmarinic acid were evolved independently in different clades. The identification of caffeic acid and rosmarinic acid UGTs from A. euchroma could lead to deeper understanding of the caffeic acid oligomers biosynthesis and its regulation. Furthermore, these UGTs might be used for regiospecific glycosylation of caffeic acid and rosmarinic acid to produce bioactive compounds for potential therapeutic applications.
Boraginaceae/genetics* ; Caffeic Acids ; Chromatography, Liquid ; Cinnamates ; Cloning, Molecular ; Depsides ; Glycosyltransferases/genetics* ; Phylogeny ; Tandem Mass Spectrometry

OBJECTIVE: To observe the distribution characteristics and rules of pain sensitivity points on body surface in patients with knee osteoarthritis (KOA). METHODS: A total of 916 patients with KOA were selected in this study, the pain sensitivity points of local site of knee joint were probed by thumb palpation. Tape was used to measure the distance between the pain sensitivity points and the most nearby acupoints. The Wagner tenderness measuring instrument was used to measure the tenderness threshold of pain sensitivity points. RESULTS: A total of 3618 pain sensitivity points were probed, among them, 3338 pain sensitivity points were sensitized. The minimum sensitization degree was 1.00, the maximum sensitization degree was 3.39, while the average sensitization degree was (2.16±0.60). Pain sensitivity points were distributed 0.37-1.73 CONCLUSION The pain sensitivity points of patients with KOA may be the expansion effect of acupoint areas in the disease states, pain sensitivity points are more likely to appear on the medial side of knee joint.
Acupuncture Points ; Humans ; Knee Joint ; Osteoarthritis, Knee/therapy* ; Pain Threshold

OBJECTIVE: To observe clinical efficacy of back arm flexion and extension combined with manipulation in treating adhesive scapulohumeral periarthritis. METHODS: From March 2016 to April 2018, 53 patients with adhesive scapulohumeral periarthritis were treated with back arm flexion and extension combined with manipulation, the main symptoms were shoulder pain and limited activity. There were 22 males and 31 females aged from 45 to 71 years old with an average of (51.63±5.79) years;the courses of disease ranged from 3 to 24 months with an average of (8.62±3.73) months. Manipulation treatment was carried out once a week, and back arm flexion and extension were performed for 3 times a day with15 movements each time, totally 4 weeks for a single course. Visual analogue scale (VAS) and Constant-Murley shoulder function score were observed and compared before treatment and one week, one and three months after treatment. RESULTS: All patients were followed up from 3 to 12 months, with an average of (5.91±3.55) months. VAS score before treatment was 4.02±1.46, and was improved to 3.15±1.54, 1.98±1.37, 1.12±0.86 respectively at one week, one and three months after treatment. Constant-Murley score before treatment was 42.70 ±5.72, and improved to 54.25 ±6.34, 67.45 ±6.84, 82.40 ±6.63 at one week, one and three months after treatment respectively;19 patients got excellent result, 22 good, 9 fair and 3 poor. CONCLUSION Back arm flexion combined with manipulation for the treatment of adhesive scapulohumeral periarthritis could effectively relieve pain, improve shoulder function, which is a simple effective treatment strategy.
Aged ; Arm ; Female ; Humans ; Male ; Middle Aged ; Periarthritis ; therapy ; Physical Therapy Modalities ; Treatment Outcome

Objective: To explore the correlation of genetic mutations and clinical features of myelodysplastic syndromes (MDS) with scores of Revised International Prognostic Scoring System (IPSS-R). Methods: Eighty-seven patients with de novo MDS were enrolled. Mutations of MDS-related genes and clinical features were used to determine the incidence and subtype of mutations. Clinical features and IPSS-R scores of the patients with high frequency mutations involving TET2, TP53, ASXL1, RUNX1 and SF3B1 genes were compared. Results: Fifty-four patients (62.1%) harbored at least one point mutation. The incidences of various mutations were significantly different, with the incidence of MDS-EB-2 being 100% and MDS-SLD being only 38.9%. Compared with the wild types, patients harboring mutations had higher lactate dehydrogenase, higher β2 microglobulin, higher percentage of bone marrow blast cells and lower hemoglobin levels (P=0.027, <0.01, <0.01, 0.046, respectively). The IPSS-R scores of MDS patients with mutations were significantly higher than the wild types (P<0.01). The IPSS-R scores of the TP53 mutation groups were 7.82±1.83, which was significantly higher than the control group (3.77±1.66, P<0.01). No difference was found between the IPSS-R between patients carrying TET2, ASXL1, RUNX1, and SF3B1 mutations or the wild types (P>0.05). Conclusion Genetic mutations are commonly found in MDS. MDS patients with mutations have unique clinical laboratory characteristics. Although the prognostic value of most genes is controversial, TP53 is an definite indicator of poor prognosis.

OBJECTIVE: To explore the clinical efficacy of acupuncture combined with granule for nerve-root type cervical spondylosis and its effects on serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and hemorheological indexes. METHODS: A total of 114 patients with nerve-root type cervical spondylosis were randomly divided into an observation group and a control group, 57 cases in each group. The patients in both groups were treated with traction. The patients in the control group were treated with oral administration of granule, 4 g each time, 3 times a day, while based on the treatment of control group, the patients in the observation group were treated with acupuncture at Dazhui (GV 14), Tianzhu (BL 10), Houxi (SI 3), cervical Jiaji (EX-B 2), Quchi (LI 11), Hegu (LI 4) and Waiguan (TE 5), once a day. Both groups were treated for 4 weeks. The simplified McGill pain questionnaire (MPQ), neck disability index (NDI), numbness score, levels of IL-6, TNF-α, IL-1β in serum and hemorheological indexes were observed before and after treatment, and the clinical efficacy was compared between the two groups. RESULTS: The total effective rate was 91.2% (52/57) in the observation group, which was higher than 71.9% (41/57) in the control group (<0.05). Compared before treatment, the scores of MPQ, NDI and numbness in the two groups were reduced after treatment (<0.05). After treatment, the scores of MPQ, NDI and numbness in the observation group were lower than those in the control group (<0.05). After treatment, the serum levels of IL-6, TNF-α and IL-1β in the two groups were reduced (<0.05), and those in the observation group were lower than the control group (<0.05). After treatment, the plasma viscosity, fibrinogen, low shear rate of whole blood viscosity and high shear rate of whole blood viscosity in the two groups were lower than before treatment (<0.05), and those in the observation group were lower than the control group (<0.05). CONCLUSION Acupuncture combined with granule have significant clinical efficacy for nerve-root type cervical spondylosis, which could reduce the serum levels of IL-6, TNF-α and IL-1β and improve hemorheology.
Acupuncture Therapy ; Humans ; Interleukin-1beta ; Interleukin-6 ; Spondylosis ; therapy ; Tumor Necrosis Factor-alpha