Objective To analyze the burden and changing trend of testicular cancer in China from 1990 to 2019.Methods Based on the 2019 Global Burden of Disease Database(GBD 2019),analyze the incidence,mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs)and their variation trend of testicular cancer in Chinese population from 1990 to 2019.Evaluating changes in age standardized rate(ASR)by calculating annual estimated percentage change(EAPC).According to the age grouping,analyze the age distribution characteristics of testicular cancer disease burden by age group.Results In 2019,the incident cases,deaths,age-standardized incidence rate,and age-standardized mortality rate of testicular cancer in China were 17.17×103,1.21×103,2.39/105,and 0.16/105,respectively.Compared to 1990,incident cases,deaths,and age-standardized incidence rate increased obviously in China,which was consistent with the global change trend,while the increase was higher than the global level.However,both Chinese and global age-standardized mortality rate showed a downward trend.From 1990 to 2019,DALYs,YLLs and YLDs of testicular cancer increased by 29.66%,9.83%and 720.91%respectively in China.The two age groups,0-15 years group and 30-35 years group,were with highest incidence of testicular cancer,while the highest disease burden of testicular cancer was 30-35 years.Conclusion From 1990 to 2019,the disease burden of testicular cancer in China showed an upward trend.Adolescents and young adults should be the priority population for screening and prevention due to their higher incidence and disease burden.

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.
Animals ; Male ; Rats ; Apoptosis ; Brain Ischemia/metabolism* ; Caspase 3 ; Interleukin-1 ; Interleukin-6 ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Flavonoids/pharmacology* ; Rhododendron/chemistry*

Humans ; Renal Artery ; Constriction, Pathologic ; Hypertension, Renovascular/therapy* ; Vascular Diseases ; Renal Artery Obstruction/therapy* ; Embolization, Therapeutic

Objective: To investigate the clinicopathological features, molecular characteristics, differential diagnosis and prognosis of anaplastic lymphoma kinase (ALK)-translocation renal cell carcinoma. Methods: Two cases of ALK-translocation renal cell carcinoma diagnosed from January 2011 to December 2020 were retrospectively analyzed to characterize their morphological features, immunohistochemical expression and prognosis. Multiple molecular studies including fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and next-generation sequencing were performed to characterize the genetic alterations. Results: Two patients included one male and one female, with 59 and 57 years old, respectively. Morphologically, case 1 resembled collecting duct carcinoma or renal medullary carcinoma, which demonstrated tubular, microcapsule and reticular structures, with a remarkable myxoid background and lymphocytes infiltration; case 2 resembled Xp11.2 translocation renal cell carcinoma or type 2 papillary renal cell carcinoma, which demonstrated tubular papillary and focal solid structures, with flocculent cytoplasm and many foamy histiocytes, but without myxoid background and lymphocytes infiltration. Immunohistochemistry showed strongly positive expression of ALK. CK7, E-cadherin, vimentin, PAX8 and CD10 showed various degrees of expression, and other antibodies were nonreactive. A variety of molecular assays showed definite ALK gene translocation, with rare VCL-ALK gene fusion (VCL exon and 16-ALK exon 20) in case 1, and EML4-ALK gene fusion (EML4 exon and 2-ALK exon 20) in case 2. Conclusions: ALK-translocation renal cell carcinoma is rare with various morphological features, and is easy to miss and misdiagnose. The characteristic ALK expression and molecular detection of ALK translocation are helpful for diagnosing this type of renal cell carcinoma.
Anaplastic Lymphoma Kinase/genetics* ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Kidney Neoplasms/genetics* ; Lung Neoplasms ; Male ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies

OBJECTIVE：To study the effects of Cu rcumin solid lipid n anoparticels （Cur-SLN） on cardiac ，renal and pulmonary functions ，the expression of autophagy related factors in cardiorenal syndrome model rats. METHODS ：The rats were divided into sham operation group ，model group ，rapamycin group （positive control ，2 mg/kg），Cur-SLN low-dose and high-dose groups（5，10 mg/kg），except for 13 rats in the model group （3 of which are used to judge whether modeling is successful ），10 rats in the other groups. Except for sham operation group ，cardiorenal syndrome of other groups were induced by abdominal aortic coarctation combined with acute renal ischemia-reperfusion injury. After successful modeling ，rats in each administration group were injected with corresponding drugs through caudal vein ，and rats in sham operation group and model group were injected with equal volume normal saline ，once a day for 4 weeks. Twenty-four hours after the last administration ，the contents of angiotensin converting enzyme （ACE），free triiodothyronine （FT3） and arginine vasopressin （AVP） in rat serum were detected. The pathological morphology of rat heart ，kidney and lung were observed. The distribution and expression of LC 3 and Beclin- 1 protein in rat heart ，kidney and lung were detected. RESULTS ：Compared with sham operation group ，the contents of ACE and FT 3 in serum，the indexes of heart and kidney ，the expression of LC 3（except in renal tissue ）and Beclin- 1 protein in heart ，kidney and lung were significantly increased （P＜0.01），and the contents of AVP and lung index were decreased significantly （P＜0.01）； myocardial cells in the non-infarcted area of the heart were obviously hypertrophic ，the arrangement of myocardial fibers was disordered ； the structure of renal tubules in the non-infarcted area of the kidney was disordered ；and there was cystic expansion and obvious inflammatory cell infiltration llittls- in the alveoli ；positive expression of LC 3 and Beclin- 1 protein nows@126.com in heart ，kidney and lung increased ，mainly distributed in the cytoplasm of cardiomyocytes ，distal renal tubular epithelial cells ，alveolar macrophages and epithelial cells. Compared with model group，the above indexes of rats in each dose group of Cur-SLN were mostly significantly reversed ；the pathological changes of heart，kidney and lung tissues were reduced ，the infiltration of inflammatory cells was reduced ；and the positive expression of LC 3 and Beclin- 1 protein were reduced ，which were mainly distributed in the cytoplasm of cardiomyocytes and proximal renal tubular epithelial cells ，and a few in distal renal tubular epithelial cells ，alveolar macrophages and epithelial cells. CONCLUSIONS ： Cur-SLN can improve the heart ，kidney and lung functions of rats with cardiorenal syndrome ，and its mechanism may be related to regulating the distribution or expression of LC 3 and Beclin- 1 protein in heart ，kidney and lung.

Objective To use World Health Organization Family International Classifications (WHO-FICs) to explore the framework and approaches of development and research of guidelines of rehabilitation at levels of policies, community and services.Methods The important documents and tools of rehabilitation at international level, including United Nations Convention on the Rights of Persons with Disabilities, WHO World Report on Disability, Community-based Rehabilitation Guideline, Rehabilitation in Health Service System, and International Classification of Diseases (ICD), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHI) of WHO-FICs, had been discussed.Results The framework, classifications, diagnosis and description of diseases and functioning, coding, intervention and functioning evaluation based on ICD-11, ICF and ICHI-β-2 had been established for development and implementation of rehabilitation guidelines and Cochrane rehabilitation.Conclusion The framework and systematic approaches of ontology, classification, terminology, coding, diagnosis and description of diseases and functioning, interventions and evaluations for the development and implementation of rehabilitation guidelines had been developed.

This study engineered β-carotene ketolase CrtW and β-carotene hydroxylase CrtZ to improve biosynthesis of astaxanthin in Escherichia coli. Firstly, crtW was randomly mutated to increase CrtW activities on conversion from β-carotene to astaxanthin. A crtW* mutant with A6T, T105A and L239M mutations has improved 5.35-fold astaxanthin production compared with the wild-type control. Secondly, the expression levels of crtW* and crtZ on chromosomal were balanced by simultaneous modulation RBS regions of their genes using RBS library. The strain RBS54 selected from RBS library, directed the pathway exclusively towards the desired product astaxanthin as predominant carotenoid (99%). Lastly, the number of chromosomal copies of the balanced crtW-crtZ cassette from RBS54 was increased using a Cre-loxP based technique, and a strain with 30 copies of the crtW*-crtZ cassette was selected. This final strain DL-A008 had a 9.8-fold increase of astaxanthin production compared with the wild-type control. Fed-batch fermentation showed that DL-A008 produced astaxanthin as predominant carotenoid (99%) with a specific titer of 0.88 g·L without addition of inducer. In conclusion, through constructing crtW mutation, balancing the expression levels between crtW* and crtZ, and increasing the copy number of the balanced crtW*-crtZ cassette, the activities of β-carotene ketolase and β-carotene hydroxylase were improved for conversion of β-carotene to astaxanthin with higher efficiency. The series of conventional and novel metabolic engineering strategies were designed and applied to construct the astaxanthin hetero-producer strain of E. coli, possibly offering a general approach for the construction of stable hetero-producer strains for other natural products.

Objective: To evaluate the safety and efficacy of dental floss traction-assisted endoscopic submucosal dissection (DFS-ESD) for rectal neuroendocrine neoplasm (NEN). Methods: A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital, Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled, including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1, and the mean size was 0.8±0.2(0.5-1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS-ESD treatment (DFS-ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS-ESD group, after the mucosa was partly incised along the marker dots, the endoscopy was extracted, and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted, the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time, modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS-ESD group), en bloc resection rate, R0 resection rate, morbidity of operative complication, recurrence and metastasis were compared between two groups. Results: The average tumor size was (0.8±0.2) cm in DFS-ESD group and (0.7±0.2) cm in conventional ESD group (t=0.425, P=0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm, 13 were G1 and 4 were G2 in DFS-ESD group, while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference (P=0.680). There were no significant differences in baseline data between in the two groups (all P>0.05). All the basal resection margins were negative, the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS-ESD group (P=0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS-ESD group (t=1.776, P=0.084). The modified operation time of DFS-ESD group was (11.9±2.8) minutes, which was significantly shorter than (17.9±6.6) minutes in conventional ESD group (t=3.425, P=0.002). The hospital stay was (2.3±0.6) days and (2.0±0.5) days in conventional ESD group and DFS-ESD group, respectively, without significant difference (t=1.436, P=0.160). No patient was transferred to surgery, and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor-related death, and all the patients recovered well during a follow-up period of 14(1-24) months. Conclusion Dental floss traction-assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.

Adult ; Cytogenetics ; Genes, p53 ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Tumor Suppressor Protein p53/genetics*

Objective To evaluate the safety and efficacy of dental floss traction?assisted endoscopic submucosal dissection (DFS?ESD) for rectal neuroendocrine neoplasm (NEN). Methods A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital ,Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled,including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1,and the mean size was 0.8±0.2(0.5?1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS?ESD treatment (DFS?ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS?ESD group,after the mucosa was partly incised along the marker dots ,the endoscopy was extracted,and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted,the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time,modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS?ESD group),en bloc resection rate,R0 resection rate, morbidity of operative complication,recurrence and metastasis were compared between two groups. Results The average tumor size was (0.8±0.2) cm in DFS?ESD group and (0.7±0.2) cm in conventional ESD group (t=0.425,P=0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm,13 were G1 and 4 were G2 in DFS?ESD group,while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference (P=0.680). There were no significant differences in baseline data between in the two groups (all P>0.05). All the basal resection margins were negative,the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS?ESD group (P=0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS?ESD group (t=1.776,P=0.084). The modified operation time of DFS?ESD group was (11.9±2.8) minutes,which was significantly shorter than (17.9±6.6) minutes in conventional ESD group (t=3.425, P=0.002). The hospital stay was (2.3 ± 0.6) days and (2.0 ± 0.5) days in conventional ESD group and DFS?ESD group,respectively,without significant difference (t=1.436,P=0.160). No patient was transferred to surgery,and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor?related death,and all the patients recovered well during a follow?up period of 14(1?24) months. Conclusion Dental floss traction?assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.