Internet-based group cognitive behavioral therapy for depression and anxiety symptoms / 四川精神卫生

This paper presents a systematic review of extant research investigating the effectiveness of Internet-based group cognitive behavioral therapy （IGCBT） for depression and anxiety symptoms with an emphasis on the treatment modalities， treatment protocols， efficacy and mechanism， together with a summary of research limitations and suggestions for future research. Cognitive behavioral therapy （CBT） is a structured， short-term and present-oriented psychotherapeutic treatment， its Internet- and group-delivered modalities have led to its wider application， and has proven to be clinically effective in alleviating depression and anxiety symptoms caused by different diseases， whereas some drawbacks have been reported. Thus this paper elaborates the clinical application， therapeutic effect and underlying mechanisms of IGCBT intervention for depression and anxiety symptoms， so as to provide references for its future application. ［Funded by the Natural Science Foundation of the Inner Mongolia Autonomous Region （number， 2019MS03038）

Modified double-tract reconstruction operation in early SiewertⅡ esophagogastric junction adenocarcinoma / 中华普通外科杂志

Objective:To evaluate the safety and efficiency of a modified double-tract reconstruction procedure─proximal gastrectomy with piggyback interposed jejunal single-channel reconstruction (PJIR-STR) for early SiewertⅡ adenocarcinoma of esophagogastric junction (AEG).Method:Data of 8 SiewertⅡ AEG patients at Shanxi Tumor Hospital and undergoing PJIR-STR from May 2018 to Oct 2019 were retrospectively analyzed. The gastroesophageal reflux disease questionnaire (GerdQ) was used to score the patients at 3, 6, 12, and 18 months after surgery. The severity of postoperative reflux esophagitis was assessed by gastroscopy at 3, 6 months after surgery, using the Los Angeles Classification criteria.Result:All patients recovered well after surgery without serious complications. No obvious gastroesophageal reflux was observed in all patients at different periods (All of the GerdQ scores were <8 points.) The results of gastroscopy showed that 1 patient was diagnosed as grade B reflux esophagitis at 3, 6 months after surgery, which was responsive to conservative treatment, and the other 7 patients had no grade B or above reflux esophagitis.Conclusion:PJIR-STR is a feasible, safe reconstruction with excellent efficiency of dual anti-reflux for the SiewertⅡ AEG.

A phase Ⅱ trial of comprehensive treatment based on radiotherapy in leptomeningeal metastasis / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of comprehensive treatment based on radiotherapy for patients with leptomeningeal metastases (LM) in this prospective study.Methods:A total of 93 patients diagnosed with LM admitted to our hospital undergoing whole brain radiotherapy (WBRT) or craniospinal irradiation (CSI) with or without simultaneous boost from 2014 to 2017 were enrolled. The dynamic changes of clinical signs and symptoms, enhanced magnetic resonance imaging (MRI), cerebrospinal fluid cytology and liquid biopsy detection were recorded. The primary endpoint was overall survival (OS), the secondary endpoints were local control (LC), intracranial progress-free survival (IPFS), brain metastasis specific survival (BMSS) and toxicity.Results:The major primary disease was non-small cell lung cancer. The whole cohort received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60 Gy in 20 f for boost), focal radiation to LM, WBRT and CSI (40 Gy in 20 f or 50 Gy in 25 f for WBRT and 36 Gy in 20 f for CSI). For 20 patients, tumor cells were identified and intrathecal chemotherapy was performed. Sixty-three patients received target therapy. The median follow-up time was 33.8 months. The 1-year OS, LC and IPFS was 62.4%, 77.2% and 52.6%, respectively. The median survival time was 15.9 months, and the median BMSS was 42.2 months. Treatment-related grade 3-4 adverse events were rare and only 8 cases was observed to have grade 3 hematological toxicity.Conclusion:Reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted therapy can be well tolerated and prolong the survival time of LM patients.

Analysis of clinical efficacy of hypofractionated precision radiotherapy for lung metastases / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of hypofractionated radiotherapy for lung metastases (LMs).Methods:From March 2007 to April 2019, 193 patients with 317 LMs including 124 male and 69 female admitted to our hospital were enrolled. The median age was 58 years old and the median KPS was 80. The primary tumors were mainly distributed in the lung (33.7%), colorectum (21.2%), head and neck (13.5%) and breast (10.9%), respectively. The clinical efficacy and side effects of hypofractionated radiotherapy for LMs were evaluated.Results:The median follow-up time was 59.9 months (95% CI: 55.1-64.6 months). Among 193 patients with 317 LMs, 90.7% of them were treated with 4D-CT, 69.4% for intensity-modulated radiation therapy (IMRT), 28.0% for volumetric-modulated arc therapy (VMAT) and 2.6% for tomotherapy (TOMO), respectively. The median gross tumor volume (GTV) and planning target volume (PTV) were 5.0 cm 3(0.2-142.3 cm 3) and 12.0 cm 3(1.0-200.1 cm 3). The prescription dose regimen was 60 Gy in 4 to 15 fractions. The median dose for PTV was 60 Gy (45-70 Gy) and biological effective dose was 96 Gy (60-150 Gy), respectively. The 1-, 3-and 5-year local control rates (LCR) were 95.7%, 91.3% and 89.9%, respectively. The median time from primary cancer diagnosis to lung metastases was a prognostic factor for LCR ( P=0.027). The overall survival (OS) and progression-free survival (PFS) rates were 90.1%, 60.8%, 46.2%, and 54.3%, 30.3%, 19.9%, respectively. The median time from primary cancer diagnosis to lung metastases and extrapulmonary metastases was the prognostic factor for OS and PFS. No Grade 3 toxicities were seen. Conclusion:Image-guided hypofractionated precision radiotherapy is an efficacious and safe treatment for LMs.

Breast board combined with a thermoplastic head mask immobilization can improve the reproducibility of the treatment setup for breast cancer patients receiving whole breast and supraclavicular nodal region irradiation / 中华放射肿瘤学杂志

Objective To quantify the setup errors measured with kV cone-beam CT (CBCT) using breast board with or without a thermoplastic head mask in breast cancer patients who received whole breast and supraclavicular nodal region irradiation.Clinical target volume (CTV) to planning target volume (PTV) in 3 directions were also calculated.Methods The study included thirty patient receiving both whole breast and supraclavicular nodal region irradiation on Elekta Versa HD linear accelerators (Elekta Oncology Systems,Crawley,UK) between June 2016 and January 2018.The setup error data were retrospectively analyzed.All the patients were immobilized in the supine position on a breast board system (Carbon fibre breast board,Civco,Iowa,USA) with both arms raised.Twenty of the patients added an extra thermoplastic head mask to immobilize the neck.A CBCT scan was taken before treatment at the first 3 to 5 fractions and then once every week.Registration with the planning CT was performed and adjusted to match the target volume of the supraclavicular nodal region and the cervical vertebra by experienced medical staff,the position of the arms and the breast were also considered.For all patients the couch shifts in left-right (x),superior-inferior (y),anterior-posterior (z) were recorded.Statistical analysis included two-tails significance tests (t-Student and Manne-Whitney test for means,x2 test for variances).Population of the two groups was compared in terms of distribution of the mean shift (systematic error) and their standard deviations (random error).Van Herk's setup margin defined as MPTV =2.5Σ + 0.7δ was calculated in patients with or without mask immobilization.Results Altogether,56 images and 109 images were acquired in breast board only group and head mask group,respectively.Shifts of the breast board only group and the head mask group in x,y,z were 0.212±0.174 cm vs.0.272±0.242 cm (P=0.070);0.364±0.246 cm vs.0.242±0.171 cm (P=0.001);0.423±0.302 cm vs.0.364±0.269 cm (P=0.204).Proportion of the shift less than 5 mm in the breast board only group and the head mask group were 91.07％ vs.85.32％ (P=0.294);67.86％ vs.89.91％ (P=0.001);67.86％ vs.74.31％ (P=0.381).The CTV to PTV margin in x,y,z were 0.645 cm,0.981 cm,1.317 cm in breast board only group and 0.873 cm,0.709 cm,0.961 cm in head mask group,respectively.Setup error in the x direction was significantly correlated with BMI (P=0.001).Conclusions For the alignment and immobilization of patients who received whole breast and supraclavicular nodal region irradiation,using a breast board in combination of a thermoplastic head mask may significantly help to reduce the shift variance in superior-inferior direction compared to using breast board only.The anterior-posterior error is relatively large,other immobilization device or patient alignment methods are needed to be further explored to improve the accuracy.

Isocenter bilateral tangential fields combined with intensity-modulated radiotherapy for synchronous bilateral whole breast irradiation / 中华放射肿瘤学杂志

Objective@#To investigate the dose characteristics and outcomes of a single isocenter bilateral tangential fields (IBTF) combined with intensity-modulated radiotherapy (IMRT) in bilateral breast radiotherapy (BBR).@*Methods@#Fourteen female patients with synchronous bilateral breast cancer (SBBC) after breast-conserving surgery (BCS) were enrolled in this study. All patients received BBR using IBTF combined with IMRT at a conventional (50 Gy/25f) or hypofractionated (43.5 Gy/15f) dose. For patients with invasive cancer, the additional tumor bed boost was given with sequential electron radiation or simultaneously photon IMRT. The coverage, uniformity and short-term clinical efficacy were evaluated.@*Results@#The number of the irradiation field was 8-11, including 4-7 intensity-modulated fields. The bilateral breast PTV dose coverage reached 95% in all plans. For the tumor bed, the mean dose coverage was (95.54±1.33)%(left) and (94.19±1.03)%(right) using photon, and (90.25±8.79)%(left) and (85.28±8.35)%(right) using electron. The average V20 of bilateral lungs was (16.69±3.90)%. The cardiac Dmean was 5.48 Gy. Three patients presented with grade Ⅱ acute skin toxicities. No ≥ grade Ⅱ pneumonitis was observed. No recurrence occurred with the median follow-up time of 30.1 months. Eleven patients showed excellent cosmetic results.@*Conclusion@#BBR using IBTF combined with IMRT is efficacious and safe for patients with SBBC after BCS.

Isocenter bilateral tangential fields combined with intensity-modulated radiotherapy for synchronous bilateral whole breast irradiation / 中华放射肿瘤学杂志

Objective To investigate the dose characteristics and outcomes of a single isocenter bilateral tangential fields (IBTF) combined with intensity-modulated radiotherapy (IMRT) in bilateral breast radiotherapy (BBR).Methods Fourteen female patients with synchronous bilateral breast cancer (SBBC) after breast-conserving surgery (BCS) were enrolled in this study.All patients received BBR using IBTF combined with IMRT at a conventional (50 Gy/25f) or hypofractionated (43.5 Gy/15f) dose.For patients with invasive cancer,the additional tumor bed boost was given with sequential electron radiation or simultaneously photon IMRT.The coverage,uniformity and short-term clinical efficacy were evaluated.Results The number of the irradiation field was 8-11,including 4-7 intensity-modulated fields.The bilateral breast PTV dose coverage reached 95％ in all plans.For the tumor bed,the mean dose coverage was (95.54± 1.33) ％ (left) and (94.19± 1.03) ％(right) using photon,and (90.25± 8.79) ％ (left) and (85.28± 8.35) ％(right) using electron.The average V20 of bilateral lungs was (16.69±3.90)％.The cardiac Dmean was 5.48 Gy.Three patients presented with grade Ⅱ acute skin toxicities.No ≥ grade Ⅱ pneumonitis was observed.No recurrence occurred with the median follow-up time of 30.1 months.Eleven patients showed excellent cosmetic results.Conclusion BBR using IBTF combined with IMRT is efficacious and safe for patients with SBBC after BCS.

Hypofractionated radiotherapy for 45 cancer patients with hepatic metastasis / 中华放射肿瘤学杂志

Objectives To evaluate the clinical efficacy and safety of hypofractionated radiotherapy for cancer patients with hepatic metastases. Methods From May 2007 to November 2016,45 patients ( male:female=20:25) with inoperable hepatic metastases were enrolled in this investigation. The median age was 58 years old ( range:25-83).The median Karnofsky performance score ( KPS) was 80.Primary colorectal cancer was detected in 14 patients,primary breast cancer in 9 and primary lung cancer in 6 cases. Twenty-one patients had extrahepatic metastases. A total of 52 lesions were treated. Thirty-four cases received radiotherapy for one single lesion. The fractional dose was 45 Gy/3 fractions and 60 Gy/10-15 fractions. The median gross tumor volume (GTV) was 10. 1 cm3(0. 3-175. 2 cm3) and 29. 8 cm3(5. 0-209. 6 cm3) for planning target volume ( PTV).Seventeen CT images were fused with MRI and IMRT was adopted in 43 cases. The median dose of PTV was 60 Gy (40-60 Gy) and 90 Gy (60-132 Gy) for bioequivalent dose (BED). Results The median follow-up time was 23. 5 months and the median survival time was 26. 0 months (95%CI:21.4-30.6 months).The 1-year local control (LC),disease-free survival (DFS) and overall survival ( OS ) were 94%, 27% and 91%, respectively. Six cases died of liver metastases and abnormal liver function. Conclusion Hypofractionated radiotherapy is an efficacious and safe local treatment for inoperable hepatic metastases.

Whole-brain irradiation with simultaneous integrated boost by helical tomotherapy for multiple brain metastases:dosimetric and clinical analyses / 中华放射肿瘤学杂志

Objective To retrospectively analyze the dosimetry and efficacy of whole-brain irradiation (WBRT) with simultaneous integrated boost (SIB) by helical tomotherapy (HT) in the treatment of multiple brain metastases (BMs),and to evaluate the feasibility,efficacy,and safety of HT.Methods From 2014 to 2017,a total of 43 patients with multiple BMs (no less than 3 lesions) were enrolled as subjects.A dose of 40 Gy was delivered to the whole brain in 20 fractions,while a dose of 60 Gy was delivered to the gross target volume (GTV) in 20 fractions.Patients were reexamined by magnetic resonance imaging during treatment.The radiation field would be shrunk if GTV was reduced.Target coverage (TC),conformity index (CI),prescription isodose/target volume (PITV) ratio,and homogeneity index (HI) were assessed.Clinical indices included local recurrence-free survival (LRFS),intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),and toxicities.Results The median lesion number was 6(3-36) and the median total volume of GTV was 8.74 cm3.The TC,CI,PITV,and HI for GTV were 0.96±0.028,0.51±0.164,2.09±1.245,and 0.12±0.066,respectively,while the TC and HI for the whole brain were 0.95±0.033 and 0.43±0.161,respectively.In all the patients,26％ had replarming during treatment.The two-stage treatment reduced the radiation dose to organs at risk.The 1-year LRFS,IPFS,PFS,and OS rates were 96％,80％,39％,and 86％,respectively.No grade ≥3 toxicities were observed.Conclusions WBRT with SIB by HT achieves satisfactory conformity,homogeneity,efficacy,and safety,which is a recommended treatment plan for multiple BMs.Replanning during treatment can better protect normal tissue.

Case-control study of fractionated stereotactic radiotherapy combined with temozolomide for large brain metastases / 中华放射肿瘤学杂志

Objective To retrospectively analyze and compare the clinical efficacy and safety between fractionated stereotactic radiotherapy (FSRT) combined with and without temozolomide in the treatment of large brain metastases.Methods Between 2009 and 2017,84 patients with large brain metastases (tumor size ≥ 6 cm3) were recruited and assigned into the CRT group (concurrent TMZ and FSRT,n=42) and RT group (FSRT alone,n=42).The radiation dose was 52.0 Gy in 13 fractions or 52.5 Gy in 15 fractions.Patients were reexamined by magnetic resonance imaging (MRI) during treatment.The radiation field would be shrunk if the gross target volume (GTV) was reduced.The clinical efficacy was evaluated at postoperative 2 to 3 months.The primary end-point event was local recurrence-free survival (LRFS) and the secondary end-point events included intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),brain metastasis-specific survival (BMSS) and adverse events.The survival rates were assessed with Kaplan-Meier method and log-rank test and monovariate analysis.Results The median GTV in the CRT and RT groups was 16.9 cm3 and 15.7 cm3.During the treatment,75％ of the lesions in the CRT group were reduced compared with 34％ in the RT group (P=0.000).The local control (LC) rate in the CRT and RT groups was 100％ and 98％.The median follow-up time was 16.1 months (range,2.1-105.7 months).In the CRT group,the LRFS (P=0.040),IPFS (P=0.022),PFS (P=0.045),OS (P=0.013) and BMSS (P=0.006) were significantly better than those in the RT group,respectively.In the CRT group,the incidence of grade Ⅰ-Ⅱ gastrointestinal adverse events was 33％,significantly higher compared with 26％ in the RT group (P=0.006).No grade Ⅳ-Ⅴ adverse events occurred in both groups.Conclusion Combined application of temozolomide and FSRT can further enhance the LC and survival rates and do not increase the risk of severe adverse events in patients diagnosed with large brain metastases.

Effects of butylphthalide on serum inflammatory cytokines and oxidative stress products in patients with acute cerebral infarction / 天津医药

Objective To investigate the effects of butylphthalide injection on serum levels of inflammatory factors and oxidative stress products in patients with acute cerebral infarction. Methods A total of 120 patients with acute cerebral infarction were selected in our hospital from March 2014 to September 2016. Patients were divided into conventional treatment group (n=56) and butylphthalide group (n=64) according the therapeutic methods. The conventional treatment group was treated with improving microcirculation and resisting blood platelet aggregation, while the butylphthalide group was injected with butylphthalide (100 mL intravenous drip, twice a day) on the basis of conventional treatment. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17, IL-23 and methane dicarboxylic aldehyde (MDA) were detected before the treatment and 7 days,14 days after the treatment. The clinical efficacy was also accessed. Results The TNF-α, IL-6, IL-17, IL-23 and MDA levels were significantly decreased 7 days and 14 days after the treatment than those before the treatment in two groups of patients (P<0.05). And the above indexes were also decreased in butylphthalide group than those of conventional treatment group (P < 0.05). No obvious adverse reactions were observed in two groups. Conclusion Butylphthalide can improve the clinical symptoms through the inhibition of inflammation and oxidative stress in patients with acute cerebral infarction.

Efficacy of hypofractionated stereotactic radiotherapy combined with temozolomide for large brain metastases:a prospective clinical study / 中华放射肿瘤学杂志

Objective To analyze the efficacy and safety of hypofractionated stereotactic radiotherapy ( FSRT ) combined with temozolomide ( TMZ ) for large brain metastases ( BMs ) in a prospective phaseⅡclinical trial.Methods From 2010 to 2015, a total of 33 patients were enrolled as subjects.The median Karnofsky Performance Status scores before and after treatment were 70 and 80, respectively.The major primary tumor was non-small cell lung cancer (57.6%).The brain metastasis had a diameter of≥3 cm or a volume of ≥6 cm3 .The radiation dose was 52 Gy in 13 fractions or 52.2 Gy in 15 fractions.Patients received TMZ at a dose of 75 mg/m2 per day concurrently.The radiotherapy was followed by 6 cycles of adjuvant treatment with TMZ (150 mg/m2, days 1-5, 28 days per cycle).Patients were reexamined by magnetic resonance imaging ( MRI) during the treatment.The radiation field would be shrunk if the gross target volume ( GTV) was reduced by≥20%.The treatment outcomes were evaluated by MRI at 2-3 months after treatment.Results The total numbers of tumors and GTVs were 95 and 38, respectively. Twenty-four (63%) out of the 38 GTVs had a volume larger than 10 cm3 and the median GTV was 15.3 cm3 (5.7-142.8 cm3).Twenty-two (67%) out of the 33 patients achieved field shrinking during the treatment, and the median reduction rate of GTV was 44%( 21%-88%) .The median total dose was 59.5 Gy, and 100%and 21.2%of patients completed the concurrent and adjuvant treatment with TMZ, respectively.In all patients, the overall response rate was 97.0%;the 1-year local control, intracranial progression-free survival, and overall survival rates were 97%, 70%, and 62%, respectively;the median survival time was 15.3 months.The main adverse reactions were grade 1-2 nausea and vomiting.One patient got grade 3 liver function impairment.Conclusions FSRT combined with TMZ is a safe and effective approach for treating large BMs.More than 50%of patients can achieve field shrinking to shorten treatment duration and reduce toxicity.Clinical Trial Registry ClinicalTrials.gov,registration number:NCT02654106.

Experimental research of immunophenotype CD133,CD34,CD44 in human lung adenocarcinoma / 中国医师杂志

Objective To validate the possibility of CD133 CD34 CD44 be served as biomarkers in cancer stem cell of human lung adenocarcinoma. Methods Two kinds of culturing methods were performed to generate adhesive tumor cells and floating aggregates, and the differences of expression of CD133 CD34 CD44 between 2 kinds of cultured cells were observed by immunofluorescence. Results Floating aggregates grew more slowly, kept activity for longer period than adhesive cells (72.5% vs 47.5%,P＜0.05). Floating aggregates expressed higher level of CD133, CD34 and CD44 than adhesive cells (68.97%,82.76%,93.10% vs 5.26%,15.79%,5.26%,P＜0.01). Conclusions The combination of CD133, CD34 and CD44 probably can be used as surface markers of cancer stem cells for human lung adenocarcinoma.

LUNX mRNA in regional lymph nodes of non-small cell lung cancer patients by RT-PCR and its clinical significance / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the detection of humen-lung-specific X protein (LUNX) gene in micrometastases of patients with non-small cell lung cancer.@*METHODS@#The expression of LUNX gene in tumor tissue, lung and lymph nodes was detected by reverse transcriptase-polymerase chain reaction(RT-PCR) both in 43 non-small-cell lung cancer patients (the experimental group) and 15 lung benign patients (the control group). LUNX mRNA expression in clinic pathology,stage of cancer cell differentiation, clinic stage, age, sex, smoking history, and 4 lung cancer blood markers (CEA,CA125,NSE, and CYFRA211) were evaluated.@*RESULTS@#The expression of LUNX gene was positive in the 2 groups. LUNX gene expression was positive in 33 of the 87 lymph nodes of the 43 patients in the experimental group (37.93%), and in 2 of the 26 lymph nodes in the control group (7.69%). The LUNX mRNA positive in the lymph nodes was closely related to the pathological type, cancer cell differentiation and clinic stage(r=0.660,0.500,0.460; P=0.011,0.017,0.022, all P0.05).@*CONCLUSION@#The LUNX mRNA expression detected by RT-PCR is more sensitive than by traditional ways. The expression of LUNX gene mRNA in the lymph nodes is a valuable index for the detection of micrometastases in patients with non-small cell lung cancer.

Gene knockout strategies for metabolic pathway regulation in industrial microbes / 生物工程学报

Gene knockout, an important technology in molecular biology, has been broadly applied in industrial microbial metabolic engineering. From the basic mechanism of DNA recombination, we summarized and compared in this review different gene knockout strategies. Three most hot and important approaches, including the lambda Red recombination system using the linear dsDNA as recombination substrate, the single or double crossover homologous recombination using the circular plasmid DNA as substrate, and the transposase mediated transposition recombination, were summarized in detail. Developing frontiers and application prospects of gene knockout were further discussed.