[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

[Prognostic analysis of definitive radiotherapy for early esophageal carcinoma(T1-2N0M0): a multi-center retrospective study of Jing-Jin-ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group].

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.

[Epidemic trend of COVID-19 in Chinese mainland].

Objective: In order to understand the epidemic trend of COVID-19 and evaluate the effect of prevention and control, this study aims to evaluate the epidemic dynamics of COVID-19 in Chinese mainland from January 16 to February 14, 2020. Methods: The daily number of new confirmed COVID-19 cases detected by nucleic acid was collected from the National Health Commission from January 16, 2020 to February 14, 2020. The analysis included the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in Chinese mainland was 50 031, including 37 930 in Hubei Province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei Province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion: The epidemic prevention and control measures taken by the state and governments at all levels have effectively curbed the spread of the COVID-19 epidemic in Chinese mainland.

Evaluation of the standardized ileal digestibility of amino acids of rapeseed meals varying in protein solubility for Pekin ducks.

This study was conducted to determine whether protein solubility (PS) of rapeseed meals (RSM) can affect standardized ileal amino acid digestibility (SIDAA) in meat ducks. A total of 1,168, 14-days-old ducks were randomly allotted to 23 treatments (6 cages per diet, 8 ducks per cage) and 1 nitrogen-free diet treatment (8 cages, 8 ducks per cage) based on body weight. The 23 experimental diets consisted of a corn-soybean meal basal diet, and 22 diets containing 15% RSM: 85% basal diet. Titanium dioxide (0.5%) was included in all diets as an indigestible marker. On day 18, all ducks were euthanized by carbon dioxide asphyxiation and digesta samples from the ileum. The contents of PS, ether extract (EE), glucosinolate, isothiocyanate, and oxazolidine were significantly different (P < 0.05) in the 22 RSM, with the CV being 52.62, 49.23, 86.84, 90.19, and 81.98%, respectively. The content of lysine (Lys) and methionine in the 22 RSM samples ranged from 1.03 to 2.71% (CV 24.19%) and from 0.33 to 0.65% (CV 15.17%), respectively. The SIDAA, except for leucine (Leu) and tyrosine, of the 22 RSM samples varied significantly (P < 0.05). A positive correlation was observed (P < 0.05) between PS and standardized ileal digestibility (SID) of Lys, isoleucine, valine, phenylalanine, histidine, serine, cysteine, and tyrosine. The R2 value of multiple linear regression equations for predicting the SID of amino acids (AA) was best for Lys (R2 = 0.958 using dry matter, crude protein, EE, crude fiber, acid detergent fiber, and PS) and least significant for Leu (R2 = 0.348 using crude fiber and ash) with intermediate values for other AA (R2 = 0.359-0.837, P < 0.05). These results suggest that PS varying from 15.06 to 98.08%, also varied considerably in the proximate nutrient content, AA composition, and antinutritional factor content, which was reflected in considerable differences in the duck's SID of AA in RSM. Therefore, PS value can partly reflect the quality of RSM.

[Evaluation of CT-guided iodine-125 seeds brachytherapy for intracranial malignant tumors under control of target and dose].

Objective: To assess the efficacy and safety of CT-guided iodine-125 seeds in the treatment of intracranial malignancies under control of target and dose. Methods: From November 2003 to May 2016, with the clinical data of 412 operations on 310 patients in 12 hospitals in the past 14 years, this study analyzed the method of CT guided iodine-125 particles brachytherapy in the treatment of intracranial malignant tumors and evaluated the efficacy and complications. Stratification analysis of intracranial malignant tumors was performed. Results: Overall survival (OS) of patients with single brain metastases, low-grade glioma, high-grade gliomas, recurrence after surgery, recurrence after radiotherapy and others were 19, 67, 41, 26, 23, 46 months respectively.And the progression free time (PFS) of patients with single brain metastases, low-grade glioma, high-grade gliomas, recurrence after surgery, recurrence after radiotherapy and others were 19, 42, 6, 9, 11, 12 months respectively.Various complications were observed with a relatively low incidence of 10.4%.Three cases deceased at an interval of 7-45 days after treatment. Conclusions: For patients with intracranial malignancies, iodine-125 seeds brachytherapy could achieve a satisfactory treatment efficacy with tolerated complications.Iodine-125 seeds brachytherapy may act as a first-line regimen.

Effects of Ti-C:H coating and plasma nitriding treatment on tribological, electrochemical, and biocompatibility properties of AISI 316L.

Ti-C:H coatings were deposited on original, nitrided, and polished-nitrided AISI 316L stainless steel substrates using a closed field unbalanced magnetron sputtering system. Sliding friction wear tests were performed in 0.89 wt.% NaCl solution under a load of 30 N against AISI 316L stainless steel, Si3N4, and Ti6Al4V balls, respectively. The electrochemical properties of the various specimens were investigated by means of corrosion tests performed in 0.89 wt.% NaCl solution at room temperature. Finally, the biocompatibility properties of the specimens were investigated by performing cell culturing experiments using purified mouse leukemic monocyte macrophage cells (Raw264.7). In general, the results showed that plasma nitriding followed by Ti-C:H coating deposition provides an effective means of improving the wear resistance, anti-corrosion properties, and biocompatibility performance of AISI 316L stainless steel.

Intravesical treatment of advanced urothelial bladder cancers with oncolytic HSV-1 co-regulated by differentially expressed microRNAs.

Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, local administration of oncolytic Herpes Simplex virus (oHSV-1) can provide a promising new therapy for this disease. However, its inherent neurotoxicity has been a perceived limitation for such application. In this study, we present a novel microRNA-regulatory approach to reduce HSV-1-induced neurotoxicity by suppressing viral replication in neurons while maintaining oncolytic selectivity toward urothelial tumors. Specifically, we designed a recombinant virus that utilizes differentially expressed endogenous microR143 (non-cancerous, ubiquitous) and microR124 (neural-specific) to regulate expression of ICP-4, a gene essential for HSV-1 replication. We found that expression of ICP-4 must be controlled by a combination of both miR143 and miR124 to achieve the most effective attenuation in HSV-1-induced toxicity while retaining maximal oncolytic capacity. These results suggest that interaction between miR143 and miR124 may be required to successfully regulate HSV-1 replication. Our resent study is the first proof-in-principle that miRNA combination can be exploited to fine-tune the replication of HSV-1 to treat human cancers.

Late Permian marine ecosystem collapse began in deeper waters: evidence from brachiopod diversity and body size changes.

Analysis of Permian-Triassic brachiopod diversity and body size changes from different water depths spanning the continental shelf to basinal facies in South China provides insights into the process of environmental deterioration. Comparison of the temporal changes of brachiopod diversity between deepwater and shallow-water facies demonstrates that deepwater brachiopods disappeared earlier than shallow-water brachiopods. This indicates that high environmental stress commenced first in deepwater settings and later extended to shallow waters. This environmental stress is attributed to major volcanic eruptions, which first led to formation of a stratified ocean and a chemocline in the outer shelf and deeper water environments, causing the disappearance of deep marine benthos including brachiopods. The chemocline then rapidly migrated upward and extended to shallow waters, causing widespread mass extinction of shallow marine benthos. We predict that the spatial and temporal patterns of earlier onset of disappearance/extinction and ecological crisis in deeper water ecosystems will be recorded during other episodes of rapid global warming.

Serological survey of Toxoplasma gondii infection in the domestic goose (Anser domestica) in southern China.

In the present study, the antibodies to Toxoplasma gondii in 191 farm-bred and 83 house-bred geese (Anser domestica) were assessed for the prevalence of T. gondii infection in southern China with the modified agglutination test. Antibodies to T. gondii (MAT ≥ 1 : 5) were found in 27 (14.14%) of farm-bred geese and 14 (16.87%) of house-bred geese. Geese infected with T. gondii may be a source of T. gondii infection for humans and cats.

An epidemiological survey of low back pain and axial spondyloarthritis in a Chinese Han population.

OBJECTIVE: To investigate the prevalence of low back pain (LBP) and axial spondyloarthritis (SpA) in a Chinese Han population. METHODS: A face-to-face investigation was performed in the Han population of Dalang Town, Yangshan County, Guangdong Province, China, using a questionnaire established in France in 1999. First the clinical features associated with SpA were investigated, then the human leucocyte antigen (HLA)-B27 and sacroiliac joint radiographic examinations were carried out. Finally, the diagnosis of SpA was determined by rheumatologists. RESULTS: A total of 13 315 subjects participated in the study and 10 921 were aged >16 years; of these, 787 (7.21%) had LBP. There were 92 axial SpA patients (0.782% in subjects >16 years old and 11.96% in subjects with LBP). There were 29 (0.253%) cases of ankylosing spondylitis (AS), 60 (0.507%) undifferentiated axial SpA (USpA), and three (0.022%) psoriatic arthritis (PsA). Patients in the SpA groups had higher percentages in onset <40 years, insidious onset, morning stiffness, and affected for >3 months compared with those in other LBP groups. Simultaneous symptoms associated with spondylitis, such as buttock pain, heel pain, psoriasis, and SpA family history, were more commonly present. Of the axial SpA patients, 82.67% were HLA-B27 positive, clearly a greater percentage than those (11.65%) in other LBP groups. CONCLUSIONS: The survey questionnaire for SpA in this study is useful for axial SpA screening in China. In southern China, the prevalence of LBP is 7.21%. The prevalence of axial SpA is 0.782%. USpA is the most common subtype of SpA, followed by AS.

Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells.

In this study, we took advantage of the overexpression of human epidermal growth factor receptor 2 (HER-2) in prostate cancers to design lentiviruses with modified envelope proteins that bind antibodies to specific cell-surface antigens. When bound to trastuzumab (Herceptin, Genentech, CA), lentiviruses were able to selectively infect androgen-sensitive LNCaP and castration-resistant C4-2 human prostate cancer cell lines, both of which express high levels of HER-2. To test for a therapeutic effect, we engineered our antibody-binding lentiviruses to express thymidine kinase, which can convert the non-toxic pro-drug ganciclovir (GCV) into a cytotoxic form. LNCaP and C4-2 cells infected by these viruses were sensitive to GCV killing. In vivo, C4-2 xenograft tumors treated either intratumorally or i.v. with trastuzumab-bound lentivirus expressed luciferase, although the latter route was less tumor specific. When a prostate-specific promoter for governing luciferase expression was combined with trastuzumab-mediated delivery, there was a further enrichment in targeting viral gene expression in prostate tumors. In conclusion, we found that although prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by viruses with envelope proteins engineered to bind this antibody.

Expression of Cdv-iR gene in mouse epididymis as revealed by in situ hybridization.

We have previously studied mouse Cdv (carnitine deficiency-associated gene expressed in ventricle)-1 related gene Cdv-1IR and its human counterpart CDV-1R, and revealed that mouse Cdv-1R was predominantly expressed in testis by multiple tissue northern analysis. To further localize the Cdv-1R mRNA in mouse testis and epididymis tissue, in situ hybridization study was reported in this article. In the adult mice, the Cdv-1R expression was intensively found in the epithelial cells of the caput and corpus epididymis, whereas it was moderately detected in the initial segment, and weakly in the cauda epididymis. In the seminiferous tubles of the testis, no obvious hybridization signals were observed above the background level. This Cdv-1R region-specific expression pattern in the epididimis suggests Cdv-1R may play an important role in sperm maturation. Moreover, considering the Cdv-1R has a similar expression distribution in epididymis to the OCTN2, it would appear that Cdv-1R might be involved in the carnitine pathway in the epididimis.

Diagnosis of Liddle syndrome by genetic analysis of beta and gamma subunits of epithelial sodium channel--a report of five affected family members.

OBJECTIVE: To screen the gene mutation in beta and gamma subunits of the epithelial sodium channel (ENaC) of a Chinese family, some of whose members are clinically diagnosed as suffering from Liddle syndrome. METHODS: Twelve family members were recruited to the study. Among them, two brothers had been clinically diagnosed as suffering from Liddle syndrome. Peripheral blood samples were collected from all members of the family and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction (PCR) was used for amplifying the last exon of beta (codon 513-673) and gamma (codon 503-632) subunits of the ENaC gene. PCR products were purified and subjected to a direct DNA sequence analysis. RESULTS: Genetic analysis of the beta ENaC gene revealed a missense mutation of CCC to CTC at codon 616 in four middle-aged men of the second generation and one young woman of the third generation. There was no mutation of the gamma ENaC gene in any of the individuals examined. CONCLUSION: Through direct DNA sequencing analysis, we diagnosed the disease present in five members of a Chinese family as Liddle syndrome, and excluded it in some other young offspring suffering from the monogenic disease. Our results provide further evidence that Pro616 is a critical amino acid that has a key role in the inhibition of sodium channel activity.

[Strategies and methods to identify genes for complex diseases].

Genes underlie numerous human diseases and traits. Although we have witnessed a great deal of success in identifying disease-susceptible genes, the task remains challenging for most of the complex diseases. This paper reviews evidence for the role of genetic factors in complex diseases, and strategies that can potentially optimize our chance of success in identifying genes involved in complex diseases. Advances in molecular biology, particularly mapping of the human genome, statistical methods that provide more accurate models of complex patterns of inheritance, and advances in basic medical science, which have increased our understanding of disease pathophysiology, will ultimately strengthen the ability of the current generation of genetic epidemiological studies to identify the genetic basis of complex human disorders.

[HLA-DQ molecules associated with myasthenia gravis in Chinese patients].

Myasthenia Gravis (MG) is an autoimmune disease which is a neuromuscular disorder of autoimmune origin. MG in different races or ethnic groups has different genetic susceptibility. To search for the associations of MG in the Chinese patients with HLA-DQ molecules, PCR-RFLP method was employed for genotyping HLA-DQA1 and -DQB1 genes of MG patients and the normal Chinese. The distributions of alleles of DQA1 and DQB1 in the normal Chinese and the MG patients were listed. The DQB allele, DQB1 * 0302 was positively associated with MG (RR = 2.990, Pc = 0.0307), and a negative association was found for DQA1 * 0501 (RR = 0.4166, Pc = 0.0315). DQ haplotype DQA1 * 0301-DQB1 * 0302 was significantly increased in patients when compared to controls (RR = 7.727, Pc = 0.0109).

Improvement of dysphagia following cricopharyngeal myotomy in a group of elderly patients. Histochemical and biochemical assessment of the cricopharyngeal muscle.

Cricopharyngeal myotomy is not effective in all cases of dysphagia. However, it should be the specific treatment in cases of dysphagia caused by a primary cricopharyngeal muscle dysfunction. Of a group of 10 patients with swallowing disorders in the absence of any defined cause, 7 (mean age, 81.6 years) were improved by a myotomy and 3 were not. The cricopharyngeal muscle was studied histologically and biochemically and compared to muscle obtained from nondysphagic subjects. In the muscle of the 7 improved patients, homogeneous histologic abnormalities were demonstrated: connective tissue infiltration, inflammatory cell infiltration, and degenerative changes of the muscle fibers. Conversely, muscles of the nonimproved patients and of the controls did not present the same degree of histologic lesions.

[Effect of biological response modifiers against pulmonary candidiasis in neutropenic mice].

We investigated the prophylactic and therapeutic effects of biological response modifiers (rHG-CSF, M-CSF, rhIL-2) on pulmonary candidiasis in neutropenic mice. Cyclophosphamide treated mice were injected by the intratracheal route with 5 x 10(6) Candida yeast cells. Prophylactic treatment with rhG-CSF afforded significant protection against pulmonary candidiasis in neutropenic mice. Treatment with rhG-CSF also increased the number of peripheral blood neutrophils. The histopathological investigations in our experiments showed that the assembly of PMNs to the infected lung at 24 hrs after bacterial challenge was more remarkable in the rhG-CSF treated mice than that in the vehicle alone. Number of viable candida cells in the infected lung in the rhG-CSF treated mice were significantly decreased. The combination of rhG-CSF and fluconazole was more effective than those of each monotherapy. Prophylactic treatment with M-CSF or rhIL-2 had no influence on pulmonary candidiasis. These results show the possibility that rhG-CSF could be of help for treating human deep candidiasis not successfully treated with antimicrobial agents alone.