Search

Cancer treatment has faced severe obstacles due to the smart biological system of cancer cells. Herein, we report a three-in-one agent Ir-CA via attenuation of cancer cell stemness with the down-regulated biomarker CD133 expression from the mitochondria-directed chemotherapy. Over 80% of Ir-CA could accumulate in mitochondria, result in severe mitochondrial dysfunctions, and subsequently initiate mitophagy and cell cycle arrest to kill cisplatin-resistant A549R cells. In vitro and in vivo antimetastatic experiments demonstrated that Ir-CA can effectively inhibit metastasis with down-regulated MMP-2/MMP-9. RNA seq analysis and Western blotting indicated that Ir-CA also suppresses the GSTP1 expression to decrease the intracellular Pt-GS adducts, resulting in the detoxification and resensitization to cisplatin of A549R cells. In vivo evaluation indicated that Ir-CA restrains the tumor growth and has minimal side effects and superior biocompatibility. This work not only provides the first three-in-one agent to attenuate cancer cell stemness and simultaneously realize anticancer, antimetastasis, and conquer metallodrug resistance but also demonstrates the effectiveness of the mitochondria-directed strategy in cancer treatment.

Ethnopharmacological Relevance: Inonotus hispidus (I. hispidus), known as shaggy bracket, has been used extensively in China and some East Asian countries as a traditional medicinal macrofungus to treat difficult diseases, such as diabetes, gout, and arthritis. Modern pharmacological research has shown that I. hispidus has an important application value in antitumor treatment. However, the main anti-cervical cancer activity substances from its mycelia and its mechanisms are still not clear., Aims of the Study: To enrich the germplasm resources of I. hispidus, to reveal the antitumor activity of the extract from the mycelium of I. hispidus against cervical cancer, and to preliminarily analyze its action mechanism., Materials and Methods: The SH3 strain was isolated from wild fruiting bodies and identified by morphology and molecular biology. The antitumor active component from the mycelium of I. hispidus was isolated and identified with liquid chromatography-tandem mass spectrometry. The cell viability was assessed by MTT assay. The cell cycle distribution, apoptotic cell detection, and mitochondrial membrane potential were detected by flow cytometer. The expression of apoptosis-related proteins was assessed by Western blotting. The inhibition of tumor growth in vivo was assessed by a mouse xenograft model., Results: The SH3 strain was isolated and identified as a new strain of I. hispidus. The antitumor active component containing cyclic peptides from the mycelium of I. hispidus (CCM) was isolated for the first time. In addition, we found that CCM had a strong inhibitory effect on HeLa proliferation in vitro and in vivo. Mechanically, the CCM blocked the cell cycle at the G0/G1 phase, decreased the mitochondrial membrane potential, and eventually promoted apoptosis of HeLa cells through the mitochondria-mediated pathway by upregulating the expression levels of Bax, cytochrome C, cleaved caspase-9, and cleaved caspase-3 and downregulating the expression level of Bcl-2., Conclusions: Our study not only enriches the strain resources of I. hispidus but also confirms that the mycelium of this strain has active components that can inhibit cervical cancer. This is highly significant for the development of active drugs and drug lead molecules for treating cervical cancer., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 μM) and kaempferol (10 μM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To compare the surgical outcome of robotic thyroidectomy through transoral approach and the bilateral breast-axillary approach. Methods: Retrospective analysis was made on the clinical data of patients who performed transoral robotic thyroidectomy (TORT group) or bilateral breast-axillary approach (BABA group) in the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from July 2020 to May 2022. Both groups received lobectomy with lymph node dissection of the central region. A total of 100 cases were included in the study, including 48 cases in the TORT group and 52 cases in the BABA group. The propensity score matching method was used for 1∶1 matching of patients between the 2 groups, with a match tolerance of 0.03. There were 31 patients in each group successfully matched. In the TORT group, there were 5 males and 26 females, aged (33.2±7.9) years (range: 21 to 53 years). While there were 4 males and 27 females in the BABA group, aged (34.6±9.2) years (range: 19 to 58 years). The t test, Mann-Whitney U test, χ 2 test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All the patients successfully completed robotic thyroid surgery without conversion to open surgery. Compared with BABA group, the TORT group had longer operation time ((211.3±57.2) minutes vs. (126.2±37.8) minutes, t =6.915, P <0.01), shorter drainage tube retention time ((5.4±1.0) days vs. (6.4±1.2) days, t =-3.544, P =0.001), shorter total hospital stay ((6.6±1.2) days vs. (7.4±1.3) days, t =-2.353, P =0.022), and higher cosmetic score (9.46±0.25 vs. 9.27±0.26, t =2.925, P =0.005). There was no significant difference between the two groups in the number of lymph nodes dissection, metastasis in the central compartment, and the incidence of postoperative complications (all P >0.05). Conclusions: Compared with the bilateral breast-axillary approach, the transoral vestibular approach of robotic thyroidectomy is also safe and effective. It shows similar surgical results to the bilateral breast-axillary approach in strictly selected patients, but the postoperative recovery speed is much faster, and the hospital stay is shorter. Transoral robotic thyroidectomy is a more recommended surgical method for patients with high aesthetic demand.

Objective: To examine the surgical outcome of transoral robotic thyroidectomy. Methods: Clinic data of total 30 cases of transoral robotic thyroidectomy at the Department of Thyroid and Breast Surgery, the 960 th Hospital of People's Liberation Army from May 2020 to December 2020 were analyzed retrospectively. There were 3 males and 27 females, aged (31.5±11.0) years (range: 17 to 55 years), including 6 cases of benign tumor and 24 cases of malignant cancer (all papillary thyroid carcinoma). An inverted U-shaped incision 1.5 cm in length was made over the end of the frenulum of the lower lip. A wide subplatysmal space was created by bluntly passing with a vascular tunneller (8 mm diameter), and a 12 mm trocar was inserted through the lip incision for the camera port. Lateral oral mucosal incisions 8 mm in length were made near both lateral labial commissures, 8 mm robot trocars were inserted through the incisions. An 5 mm trocar was inserted through an incision made along the patient's right axillary fold into the subplatysmal working space and was connected with 5 mm ProGrasp for counter traction during the operation and for later drain insertion. Numerical scoring system (NSS) was used to assess cosmetic effect 1 month post-operation. Results: All the 30 transoral robotic thyroidectomies was successful, no case conversed to open operation. Postoperative hospital stay was (6.3±1.2) days (range: 4 to 10 days). The tumor size of thyroid cancers was (5.3±3.0) mm (range: 2 to 15 mm). Lymph node metastasis was observed in 12 cases. The retrieved central lymph node number was 10.5±4.4 (range: 4 to 20), while the central metastatic lymph node number was 2(2) (range: 1 to 11). Postoperative transient hypoparathyroidism occurred in 2 cases. Permanent hypoparathyroidism and vocal cord palsy didn't occur. Other surgical complications included hematoma, surgical site infection and perforation of chin flap, retrospectively in 1 case. Local regional lymph node recurrence wasn't developed during 1 to 7 months follow-up. All patients were satisfied with the postoperative cosmetic outcomes,NSS was 9.4±0.8 (range: 8.7 to 9.6). Conclusion: Transoral robotic thyroidectomy is safe and effective, suitable for early thyroid cancers without lateral lymph node metastasis, and has superior cosmetic results when the patients are selected carefully.

Objective: To examine the surgical outcome, completeness and safety of robotic thyroidectomy by bilateral axillo-breast approach (BABA). Methods: From February 2014 to May 2019, 1 000 cases of robotic thyroidectomy via BABA at the Department of Thyroid and Breast Surgery, the 960 th Hospital of People's Liberation Army were performed. The clinicopathologic characteristics, operation times, perioperative complications, and oncologic outcomes of patients underwent robotic thyroidectomy were collected and reviewed retrospectively. There were 216 males and 784 females, aging (42.3±11.5) years (range: 7 to 75 years). There were 270 cases with benign tumors, and 730 cases with malignant cancers (the tumor diameter was (7.9±6.7) mm (range: 0.1 to 60.0 mm)). Results: There were 999 patients received robotic thyroidectomy using BABA approach successfully, while only 1 case conversed to open operation. The postoperative hospital stay was (7.5±2.5) days (range: 2 to 30 days). Among the 730 patients with thyroid cancers, 725 cases (99.3%) were papillary thyroid carcinoma, 579(79.3%) cases were with papillary thyroid microcarcinoma. Lymph node metastasis was observed in 371(50.8%) cases. The retrieved central lymph node number was 11.2±6.1 (range: 1 to 44),and the retrieved lateral lymph node number was 14.0±8.8 (range: 1 to 52). Postoperative transient hypoparathyroidism and vocal cord palsy occurred in 247(24.70%) and 56(5.60%) cases. Both of permanent hypoparathyroidism and vocal cord palsy occurred in 2 (0.20%) cases. Other surgical complications included chyle leakage (6.1%, 28/460), trachea injury (0.40%, 4/1 000), carotid artery injury (0.10%, 1/1 000). Local regional lymph node recurrence was developed in 4 patients. All patients were satisfied with the postoperative cosmetic outcomes. Conclusions: Robotic thyroidectomy by BABA is safe and effective, suitable for large benign tumors and early thyroid cancers with central or lateral lymph node metastasis. It could obtain superior cosmetic results.

Background: The consistency in steatosis grading between magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and controlled attenuation parameter (CAP) before and after treatment remains unclear. This study aimed to compare the diagnostic accuracy of steatosis grading between MRI-PDFF and CAP using liver biopsy as standard and to evaluate the value of monitoring changes in steatosis grading with CAP during follow-up utilizing MRI-PDFF as a reference., Methods: Consecutive patients from a biopsy cohort and a randomized controlled trial were included in this study and classified into 3 groups (the biopsy, orlistat treatment, and routine treatment subgroups). Hepatic steatosis was measured via MRI-PDFF and CAP at baseline and at the 6th month; the accuracy and cutoffs were assessed in the liver biopsy cohort at baseline., Results: A total of 209 consecutive patients were enrolled. MRI-PDFF and CAP showed comparable diagnostic accuracy for detecting pathological steatosis [⩾S1, area under the receiver operating characteristic curve (AUC) = 0.984 and 0.972, respectively]; in contrast, CAP presented significantly lower AUCs in grades S2-3 and S3 (0.820 and 0.815, respectively). The CAP values correlated well with the MRI-PDFF values at baseline and at the 6th month ( r  = 0.809 and 0.762, respectively, both p  < 0.001), whereas a moderate correlation in their changes ( r  = 0.612 and 0.524 for moderate-severe and mild steatosis, respectively; both p  < 0.001) was observed. The AUC of CAP change was obtained to predict MRI-PDFF changes of ⩾5% and ⩾10% (0.685 and 0.704, p  < 0.001 and p  = 0.001, respectively). The diagnostic agreement of steatosis grade changes between MRI-PDFF and CAP was weak (κ = 0.181, p  = 0.001)., Conclusions: CAP has decreased value for the initial screening of moderate-severe steatosis and is limited in monitoring changes in steatosis during treatment. The confirmation of steatosis grading with MRI-PDFF remains necessary., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

The myodural bridge (MDB) is a dense connective tissue bridge connecting the suboccipital muscles to the spinal dura mater, and it has been proven to be a normal common existing structure in humans and mammals. Some scholars believe that the suboccipital muscles can serve as a dynamic cerebrospinal fluid (CSF) pump via the MDB, and they found head rotations promote the CSF flow in human body, which provided evidence for this hypothesis. Head movement is a complex motion, but the effects of other forms of head movement on CSF circulation are less known. The present study explored the effects of head-nodding on CSF circulation. The CSF flow of 60 healthy volunteers was analyzed via cine phase-contrast magnetic resonance imaging at the level of the occipitocervical junction before and after one-minute-head-nodding period. Furthermore, the CSF pressures of 100 volunteers were measured via lumbar puncture before and after 5 times head-nodding during their anesthetizing for surgical preparation. As a result, it was found that the maximum and average CSF flow rates at the level of the upper border of atlas during ventricular diastole were significantly decreased from 1.965 ± 0.531 to 1.839 ± 0.460 ml/s and from 0.702 ± 0.253 to 0.606 ± 0.228 ml/s respectively. In the meantime, the changes in the ratio of cranial and caudal orientation of the net flow volume were found differed significantly after the one-minute-head-nodding period (p = 0.017). And on the other hand, the CSF pressures at the L3-L4 level were markedly increased 116.03 ± 26.13 to 124.64 ± 26.18 mmH 2 O. In conclusion, the head-nodding has obvious effects on CSF circulation and head movement is one of the important drivers of cerebrospinal fluid circulation. We propose that the suboccipital muscles, participating in various head movements, might pull the dura sac via the myodural bridge, and thus, head movement provides power for the CSF circulation., (© 2021. The Author(s).)

Hepatocellular carcinoma (HCC) is a frequently seen malignant tumor globally. The occurrence of cisplatin (DDP) resistance is one of the main reasons for the high mortality of HCC patients. Therefore, it is of great theoretical significance and application value to explore the mechanism of chemotherapy resistance. Drug resistance can be modulated by exosomes containing mRNAs, micro RNAs (miRNAs) and other non-coding RNA (ncRNAs). Exosomal miR-199a-3p (Exo-miR-199a-3p) was subjected to extraction and verification. Whether exo-miR-199a-3p could make HCC cells sensitive to DDP in vitro was verified via flow cytometry, Cell Counting Kit-8 (CCK-8) assay, immunofluorescence assay and Transwell assay. Intravenous injection of exo-miR-199a-3p and intraperitoneal injection of DDP were carried out in vivo. Moreover, the possible targets of miR-199a-3p were screened through bioinformatics analysis, which were ascertained by Western blotting (WB). Then, miR-199a-3p levels in human normal liver epithelial cell line HL-7702 and HCC cell lines HuH7 and HuH7/DDP were elevated in a concentration-dependent manner. Exo-miR-199a-3p has abilities to adjust underlying targets and conjugate cells, to repress cells to invade, stimulate their apoptosis and abate their ability. Additionally, the caudal injection of exo-miR-199a-3p reversed the chemoresistance of tumors and slowed down their growth in the body owing to the up-regulation of miR-199a-3p and down-regulation of underlying target proteins in tumors. Finally, exo-miR-199a-3p was found to overturn the HCC's resistance to DDP, and it may function in DDP-refractory HCC therapy as an underlying option in the future., (© 2020 The Author(s).)

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) μmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) μmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) μmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

We determined the effects of enhanced recovery after surgery (ERAS) in patients undergoing radical surgery for gastric carcinoma. Sixty patients undergoing radical gastrectomy for gastric carcinoma in Lishui Hospital between March and October 2016 were randomized to receive either ERAS (30 patients) or conventional care (30 patients, controls). Clinical, economic, and laboratory indices were analyzed. ERAS patients showed faster recovery and shorter postoperative hospital stays than the controls (P<0.05). Some clinical indices (i.e., time to first flatus and defecation, time to removal of drainage tubes, time to resumption of oral feeding, time to postoperative mobilization, and postoperative complications) were significantly better in ERAS patients than in controls. Duration of postoperative infusion was lower in ERAS patients than in controls (P<0.05). In ERAS patients, serum albumin and prealbumin were higher on postoperative day 7, C-reactive protein was lower on postoperative days 3 and 7, and neutrophil count was lower on postoperative day 3 compared to the values in controls (P<0.05 for all). IgM levels were higher in ERAS patients on postoperative days 3 and 7 (P<0.05), while IgG levels were higher on postoperative day 3 (P<0.05). Total T lymphocytes were higher in ERAS patients on postoperative day 3, while helper T cells and CD4+/CD8+ ratio were higher on postoperative days 3 and 7 (P<0.05 for all). In gastric carcinoma patients, ERAS may reduce perioperative inflammation, improve immunity and postoperative nutrition, shorten hospitalization, and enhance rehabilitation.

Although several optimal mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR) loci have been suggested for genotyping homogenous Mycobacterium tuberculosis, including the Beijing genotype, a more efficient and convenient selection strategy for identifying optimal VNTR loci is needed. Here 281 M. tuberculosis isolates were analyzed. Beijing genotype and non-Beijing genotypes were identified, as well as Beijing sublineages, according to single nucleotide polymorphisms. A total of 22 MIRU-VNTR loci were used for genotyping. To efficiently select optimal MIRU-VNTR loci, we established accumulations of percentage differences (APDs) between the strains among the different genotypes. In addition, we constructed a minimum spanning tree for clustering analysis of the VNTR profiles. Our findings showed that eight MIRU-VNTR loci displayed disparities in h values of ≥0.2 between the Beijing genotype and non-Beijing genotype isolates. To efficiently discriminate Beijing and non-Beijing genotypes, an optimal VNTR set was established by adding loci with APDs ranging from 87.2% to 58.8%, resulting in the construction of a nine-locus set. We also found that QUB11a is a powerful locus for separating ST10s (including ST10, STF and STCH1) and ST22s (including ST22 and ST8) strains, whereas a combination of QUB11a, QUB4156, QUB18, Mtub21 and QUB26 could efficiently discriminate Beijing sublineages. Our findings suggested that two nine-locus sets were not only efficient for distinguishing the Beijing genotype from non-Beijing genotype strains, but were also suitable for sublineage genotyping with different discriminatory powers. These results indicate that APD represents a quantitative and efficient approach for selecting MIRU-VNTR loci to discriminate between divergent M. tuberculosis sublineages.

Hypoxia is common in solid tumors and results in the activation of hypoxia-response genes. Hypoxia-inducible factor-1α (HIF-1α) is thought to reflect major cellular adaptation to hypoxia and contributes to chemoresistance in various tumors including hepatocellular carcinoma (HCC). N1-guanyl-1,7-diaminoheptane (GC7) is an inhibitor which suppresses the active eukaryotic translation initiation factor 5A-2 (eIF5A2), preventing epithelial-mesenchymal transition (EMT) in chemoresistance. In this study, we investigated the role of GC7 in the therapeutic effect of doxorubicin in hypoxia in HCC. We utilized four types of HCC cell line (Huh7, Hep3B, SNU387 and SNU449) in this study. Western blot and immunofluorescence were used to detect expression of epithelial/mesenchymal markers for EMT evaluation and HIF-1α was knocked down using HIF-1α-siRNA. Hypoxia-induced EMT contributed to doxorubicin chemoresistance in HCC cells. Low concentrations of GC7 sensitized Huh7 and Hep3B to doxorubicin by reversing EMT. Knockdown of HIF-1α attenuated hypoxia-induced EMT and abolished the unique feature of GC7. GC7 enhanced sensitivity to doxorubicin in HCC by reversing hypoxia-induced EMT via the HIF-1α-mediated signaling pathway. We suggest a new method of enhancing cytotoxicity of chemotherapy and improving the long-term survival rate in HCC., Competing Interests: None.

The SCN1A gene with 1274 point mutations in the coding regions or genomic rearrangements is the most clinically relevant epilepsy gene. Recent studies have demonstrated that variations in the noncoding regions are potentially associated with epilepsies, but no distinct mutation has been reported. We sequenced the 5' upstream region of SCN1A in 166 patients with epilepsy and febrile seizures who were negative for point mutations in the coding regions or genomic rearrangements. A heterozygous mutation h1u-1962 T > G was identified in a patient with partial epilepsy and febrile seizures, which was aggravated by oxcarbazepine. This mutation was transmitted from the patient's asymptomatic mother and not found in the 110 normal controls. h1u-1962 T > G was located upstream the most frequently used noncoding exon and within the promoter sequences. Further experiments showed that this mutation decreased the promoter activity by 42.1 % compared with that of the paired haplotype (P < 0.001). In contrast to the null expression that results in haploinsufficiency and severe phenotype, this mutation caused relatively less impairment, explaining the mild epilepsy with incomplete penetrance. The antiepileptic drug-induced seizure aggravation in this patient suggests clinical attention for mutations or variations in noncoding regions that may affect SCN1A expression.

Background: The spread of multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M. tuberculosis) strains has been a big challenge to the TB control and prevention in China. Knowledge about patterns of drug resistance in TB high-burden areas of China is crucial to develop appropriate control strategies. We conducted a comprehensive investigation of the resistance pattern of M. tuberculosis in Heilongjiang Province., Methods: 1427 M. tuberculosis clinical strains were isolated from pulmonary TB patients hospitalized between 2007 and 2012. The susceptibility of the isolates to the first-line anti-TB drugs and the resistance of MDR M. tuberculosis to fluoroquinolones were examined. We also performed a statistical analysis to identify the correlated risk factors for high burden of MDR-TB., Results: The global resistance rates of 2007-2012 to the first-line drugs and MDR were 57.0 and 22.8 %, respectively. Notably, the primary MDR-TB and pan-resistance rates were as high as 13.6 and 5.0 %, respectively. Of MDR M. tuberculosis isolates (2009), approximately 13 % were not susceptible to any of the fluoroquinolones tested. Being age of 35 to 54, high re-treatment proportion, the presence of cavity lesion, and high proportion of shorter hospitalization are correlated with the development of MDR-TB., Conclusions: The high prevalence of drug resistant, MDR-TB, and fluoroquinolone-resistant MDR-TB is a big concern for TB control. More importantly, in order to control the development of MDR-TB effectively, we need to pay more attention to the primary resistance. Targeting reducing the prevalence of the risk factors may lead to better TB control in China.

Introduction: Leiomyoma of the bladder is a rare tumor arising from the submucosa. Most patients with bladder leiomyoma may present with urinary frequency or obstructive urinary symptoms. However, there are a few cases of bladder leiomyoma coexisting with uterine leiomyoma presenting as dyspareunia. We herein report an unusual case of coexisting bladder leiomyoma and uterine leiomyoma presenting as dyspareunia., Case Presentation: A 44-year-old Asian female presented to urologist and complained that she had experienced dyspareunia over the preceding several months. A pelvic ultrasonography revealed a mass lesion located in the trigone of urinary bladder. The mass lesion was confirmed on contrast-enhanced computed tomography (CT). The CT scan also revealed a lobulated and enlarged uterus consistent with uterine leiomyoma. Then, the biopsies were then taken with a transurethral resection (TUR) loop and these biopsies showed a benign proliferation of smooth muscle in a connective tissue stroma suggestive of bladder leiomyoma. An open local excision of bladder leiomyoma and hysteromyomectomy were performed successfully. Histological examination confirmed bladder leiomyoma coexisting with uterine leiomyoma., Conclusion: This case highlights a rare presentation of bladder leiomyoma, dyspareunia, as the chief symptom in a patient who had coexisting uterine leiomyoma. Bladder leiomyomas coexisting with uterine leiomyomas are rare and can present with a wide spectrum of complaints including without symptoms, irritative symptoms, obstructive symptoms, or even dyspareunia.

Objective: To study the physical activity level and its influence factors among residents in one suburb of Beijing, so as to provide specific interventions for different people in different circumstances and to provide reference for health relevant policy-making in the future., Methods: In the study, 7 319 subjects aged 18 years or above were involved. The self-designed questionnaires based on Health Belief Model (HBM) had acceptable validity and reliability. The physical activity levels were calculated to classify sufficient or insufficient amount by a thousand-step equivalent greater than or equal to 6 or 10. Multiple variable Logistic regression was used to explore the influence factors of the physical activity among the residents., Results: The residents' median amount of physical activity in the suburb district of Beijing were 9.1 thousand-step equivalent with quartile of (3.8, 20.4). The percentages of the thousand-step equivalent greater than or equal to 6 or 10 were 63.7% and 47.7%, respectively. The median amounts of physical activity from work or household chores, transportation and recreation physical activities were 4.0, 1.0, 0.0 and the components of the total amount of physical activity from those were 61.7%, 18.3% and 20.1%, respectively. There were 8.6% residents whose life did notinvolve moderate or vigorous intensity activities. By using factor analysis, five factors were extracted from the scale based on the HBM; These factors together contributed to 63.7% of the sum of the squared loadings. The differences of physical activity levels on education level, age, gender, self-efficacy, cues, subjective and objective barriers were statistically significant (P<0.05).Those who were female, with older age, lower education level, higher self-efficacy, fewer cues, fewer subjective and objective barriers preferred to do more physical activities., Conclusion: The physical activity levels among the residents in the suburb district of Beijing are moderate and high, and most amount of physical activities from work or household chores. Those who are male and whose ages are from 18 to 29 years and whose education levels are of university or above should be focused on intervention. Specific interventions should be developed for different people in different situations; More attention should be paid to improve the residents' self-efficacy and reduce the subjective and objective barriers of physical activity, and we also should actively advocate people to have more leisure exercise so as to improve the physical activity level among all residents.

Euthyroid multinodular goiters may lead to acute respiratory failure caused by airway obstruction or laryngotracheal compression. Here, we present a case admitted to the nephrologist with multinodular goiter spontaneous hemorrhage along with respiratory failure and end-stage renal disease (ESRD), which required urgent surgical intervention.We report the case of a 63-year-old woman with ESRD who presented with a rapidly enlarging nodular goiter resulting in acute respiratory failure. Endotracheal intubation and emergency partial thyroidectomy were performed, revealing multinodular goiter spontaneous hemorrhage by postoperative histopathology. Several cases of benign goiters necessitating endotracheal intubation have been reported. Goiters are among the rare diagnoses in patients consulting at our institution's Nephrology.This case illustrates that ESRD patients with benign goiter may lead to acute respiratory failure due to airway obstruction or laryngotracheal compression. It was found in agreement with previous reports. This case highlights that ESRD patient at risk of this life threatening complication such as multinodular goiter hemorrhage should be managed with elective thyroidectomy to reduce morbidity and mortality.

Immunoglobulin G4-related disease is a recently recognized systemic disease that can affect any organ or tissue in the body, including the kidneys. IgG4-related kidney disease (IgG4-RKD) is an important part of immunoglobulin G4-related disease. The most common renal manifestation of IgG4-RKD is tubulointerstitial nephritis and glomerular lesions. There, however, is few case of IgG4-RKD mimicking malignant ureter tumor leading to severe hydronephrosis. We herein report an unusual case of IgG4-RKD mimicking malignancy.A 66-year-old Asian man presented to the nephrologist with soreness of loins, anorexia, and acute kidney injury in 2010. His renal function spontaneously improved after 2 weeks' hemodialysis without systemic steroid therapy. Four years later, he presented to the urologist with severe left hydronephrosis because of marked thickness of the left ureter wall. As a ureteral malignancy could not be ruled out, laparoscopic nephroureterectomy was performed.IgG4-related kidney disease was confirmed by the histologic examination. Then, repeat laboratory test showed almost complete recovery of renal function after initiation of steroidal therapy.This case highlights the rare possibility of IgG4-RKD mimicking malignant ureter tumor. Nephrologist and pathologists should be aware of the possibility that hydronephrosis with ureter obstruction may be involved in IgG4-RKD., Competing Interests: The authors have no conflicts of interest to disclose.

Long non-coding RNA (lncRNA) is commonly defined as an RNA with a length of greater than 200 nucleotides, frequently up to 100 kb. Numerous studies have shown that dysregulation of lncRNAs may directly relate to a number of human diseases, particularly in oncology where lncRNAs appear to play an important role. LncRNAs may also play a potentially novel and critical role in the development and progression of hepatocellular carcinoma (HCC). This article discusses lncRNAs as a new possibility for diagnostic and therapeutic approaches for HCC. The authors introduce the relationship between some lncRNAs and HCC, including carcinogenesis, development, metastasis and prognosis. In addition, the authors suggest that the discovery of lncRNAs may encourage the discovery and development of new therapeutic modalities for HCC and that their regulation may be a promising potential treatment for HCC. Clinical studies are required to determine the therapeutic effect of regulating lncRNA in humans with HCC.

Soil respiration (Rs) is a major pathway for carbon cycling and is a complex process involving abiotic and biotic factors. Biological soil crusts (BSCs) are a key biotic component of desert ecosystems worldwide. In desert ecosystems, soils are protected from surface disturbance by BSCs, but it is unknown whether Rs is affected by disturbance of this crust layer. We measured Rs in three types of disturbed and undisturbed crusted soils (algae, lichen, and moss), as well as bare land from April to August, 2010, in Mu Us desert, northwest China. Rs was similar among undisturbed soils but increased significantly in disturbed moss and algae crusted soils. The variation of Rs in undisturbed and disturbed soil was related to soil bulk density. Disturbance also led to changes in soil organic carbon and fine particles contents, including declines of 60-70% in surface soil C and N, relative to predisturbance values. Once BSCs were disturbed, Q 10 increased. Our findings indicate that a loss of BSCs cover will lead to greater soil C loss through respiration. Given these results, understanding the disturbance sensitivity impact on Rs could be helpful to modify soil management practices which promote carbon sequestration.

In this study, the influence of isoleucine and arginine on the biological activity and peptide-membrane interactions of linear avian β-defensin-4 (RL38) analogs was investigated. Results of biological activities showed that the antimicrobial activities of AvBD-4 analogs were closely related to hydrophobicity and amphipathicity. The peptide GLI19 with high hydrophobicity value and amphipathicity displayed broad spectrum antimicrobial activity against both gram-negative and gram-positive, whereas GLR19 with increasing multiple charges only exhibited activity against gram-negative. The interaction between peptides and the liposome membrane demonstrated that the peptides preferentially bound to negatively charged phospholipids over zwitterionic phospholipids, which supported the antimicrobial activity data. The outer membranes assay further demonstrated that GLI19 had a greater capacity than the other tested peptides to penetrate the cell membrane at a low concentration. Collectively, the peptides derived from the bactericidal domain of linear β- defensins by truncation and hydrophobic amino acid substitution may be effective high-potential antibacterial agents.

Objective: To discuss the computerized tomography (CT) finding of early postoperative inflammatory small bowel obstruction (EPISBO) so as to enhance its diagnostic level., Methods: The CT findings of 35 EPISBO cases proved by surgery were retrospectively analyzed from August 2003 to October 2008., Results: The main CT findings were as follows: (1) Incomplete small bowel obstruction; (2) Thickening and edema of focal or global bowel wall; (3) Local or diffuse effusion mainly around operative incision; (4) Without definite obstruction point or bent adhesive point; (5) Locally ring-shaped or delayed enhancement during an enhancement scan., Conclusion: Spiral CT has an important value in the diagnosis of EPISBO.

Low temperature stress during germination and early seedling growth is an important constraint of global production of maize. The effects of seed priming with 0.25%, 0.50%, and 0.75% (w/v) chitosan solutions at 15 degrees C on the growth and physiological changes were investigated using two maize (Zea mays L.) inbred lines, HuangC (chilling-tolerant) and Mo17 (chilling-sensitive). While seed priming with chitosan had no significant effect on germination percentage under low temperature stress, it enhanced germination index, reduced the mean germination time (MGT), and increased shoot height, root length, and shoot and root dry weights in both maize lines. The decline of malondialdehyde (MDA) content and relative permeability of the plasma membrane and the increase of the concentrations of soluble sugars and proline, peroxidase (POD) activity, and catalase (CAT) activity were detected both in the chilling-sensitive and chilling-tolerant maize seedlings after priming with the three concentrations of chitosan. HuangC was less sensitive to responding to different concentrations of chitosan. Priming with 0.50% chitosan for about 60 approximately 64 h seemed to have the best effects. Thus, it suggests that seed priming with chitosan may improve the speed of germination of maize seed and benefit for seedling growth under low temperature stress.

Objective: To evaluate the spiral CT and its reconstruction techniques in diagnosis and localization of gastrointestinal stromal tumor originated in the small intestine., Methods: The data of spiral CT scan and MPR, STS-MIP of 24 patients with gastrointestinal stromal tumor in the small intestine confirmed pathologically were analyzed retrospectrvely., Results: Of 24 cases, 1 had multiple tumor, while the other 23 had single one. Seventeen of these tumors were benign and 7 malignant, with 2 in the duodenum, 12 in the jejunum and 10 in the ileum. The range of tumor diameters was from 2.5 to 12 cm. The main clinical characters of the tumors on the CT image: (1) The tumor of 15 cases located outside of the enteric cavity, 7 inside of the enteric cavity or presented as thicken bowel wall and 2 showed as niche sign. (2) The tumor shape of 19 cases were round-like, and 5 lobulated or irregular. (3) The tumor density of 12 cases was homegeneous, 7 heterogeneous and 5 map-like in the center. (4) The tumor enhancement style in 19 cases were homegeneous in dynamic enhanced scan, and 16 were slightly or mildly heterogeneous in the artery phase but apparently enhanced in the venous and equilibrium phase, with 5 showed as fast-in fast-out enhanced mode. Of those, one showed obvious enhancement in artery phase, while 2 did not. (5) The tumor of 2 cases had no clear margin and had invaded the surrounding tissue. (6) The arteries supplying tumors in 20 cases were demonstrated by multiple planar reconstruction (MPR), sliding thin slab-maximum intensity projection (STS-MIP). The accuracy of diagnosis and localization of gastrointestinal stromal tumor in the small intestine by spiral CT scan combined with MPR, STS-MIP were 91.7% (22/24) and 95.8% (23/24), respectively., Conclusion: Spiral CT and its reconstruction techniques (MPR, STS-MIP) can play an important role in the differential diagnosis and localization of gastrointestinal stromal tumor originated in the small intestine.

Objective: To evaluate the value of spiral computed tomography (CT) in diagnosis of adult intussusception., Methods: Sixty-eight patients with adult intussusception, 42 males and 28 females, aged 52.5 (30-82), with the course of 3 days-13 months, underwent plain CT scanning and biphase CT enhanced scanning of the abdomen. Operation was performed later., Results: Sixty-six of the 68 patients (97.1%) were diagnosed as with intussusception by spiral CT. Direct signs of intussusception were shown in 66 patients: concentric circle sign in 66 cases, vessel involvement in 61 cases, and fat sign in 58 cases. And main indirect signs were shown in 19 cases: ring sign in 19 cases, ileus sign in 24 cases, and ascitic fluid sign in 4 cases. Other signs included mesenteric infiltration in 4 cases and retroperitoneal lymphadenectasis in 8 cases. Operation performed later showed an accurate rate of etiological diagnosis of intussusception by CT of 72.1%., Conclusion: Spiral CT has important value in diagnosis of adult intussusception and its etiology. The specific signs to diagnose adult intussusception are concentric circle sign, vessel involvement and fat sign.

Objective: To explore the epidemiological status of disabilities on vision impairment (VI), hearing loss (HL), mental retardation (MR), autism spectrum disorder (ASD) and motor disorder (MD) in aged 0-6 years old children in Beijing., Methods: A total of 28 738 children under 7 years old were recruited from permanent residents of Beijing City by 2-phase cluster sampling. The screening procedure was 2-phase, and the diagnosis criteria were developed by the experts group., Results: The overall disability rate was 11.45 per thousand (95 % CI:10.22-12.68). The false negative rates in HL and ASD were 0.14 per thousand, 0.80 per thousand, respectively, with a adjusted overall rate of 12.19per thousand. The prevalence rates of different kind disabilities from high to low were MR 9.31per thousand, MD 2.12per thousand, ASD 1.53per thousand (0.73per thousand before adjusted), HL 1.04per thousand (0.91per thousand before adjusted) VI 0.73per thousand. The results of logistic regression analysis showed that the possible non-biological risk factors for those disabilities were being male, living in city area, advancing age, mother with low education, mother engaged in labor work, and family with low income. It was primarily (49.62%) those prenatal factors other them the known suspected factors that causing disabilities., Conclusions: Compared with data from a countrywide study in 1987, the overall disability rate had a mild decrease (16.36%) with the most (56.85%) appeared in HL. It is indispensable to establish a disabilities surveillance program for the early recognition and intervention of children with disabilities. It is also crucial to clarify a disability definition for children combined with their characteristics of growth and development. We strongly recommended in developing a new definition on children' disabilities and establishing new criteria according to the contents of developmental disabilities of Center for Disease Control, USA.

Objective: To assess the effect of tea consumption on the risk of endometrial cancer., Methods: In a population based case-control study conducted in urban Shanghai, face-to-face interviews were completed for 995 incidence cases aged 30 - 69 from January 1997 to December 2002 and 1087 controls that frequency-matched to cases on age. Unconditional logistic model was used for analysis., Results: An inverse association was observed in tea drinking and endometrial cancer risk. Compared to non-tea drinkers, regular tea drinkers had reduced risk of endometrial cancer (OR = 0.74; 95% CI: 0.54 - 1.01) in premenopausal women. Green tea had a protective effect on endometrial cancer among non-smoking or non-alcohol drinking women (OR = 0.77, P = 0.0199) and the ORs reduced with the increasing concentration of tea being served (P for trend = 0.0493). The multivariate ORs for drinking green tea < 7 times/week and >or= 7 times/week were 0.90 (95% CI: 0.53 - 1.54) and 0.76 (95% CI: 0.60 - 0.95) with the trend test of P = 0.0163., Conclusion: Tea drinking, with green tea in particurlar, seemed to have weak but inverse association with endometrial cancer risk, but this effect of protection might only limit to premenopausal women.

Objective: To determine whether the anatomic characteristics of the left hepatic vein, middle hepatic vein and common trunk could influence the operation procedures of left hepatectomy., Method: Fifteen fresh human liver specimens were dissected and their anatomic characteristics were recorded., Results: The left hepatic vein and middle hepatic vein formed the common trunk of 1.2+/-0.4 cm in length in the 15 liver specimens. The angle between the left hepatic vein and middle hepatic vein was 91+/-18.3 degree., Conclusion: The left hepatic vein should not be sutured and ligated blindly in left hepatectomy because there might be a potential damage to the middle hepatic vein.

Background: In cases of right hepatectomy for huge tumour encroaching onto the diaphragm, the 'anterior approach' is the most common surgical procedure undertaken. The 'liver hanging manoeuvre' has been described previously as an adjunct to this procedure. It involves the dissection of a retrohepatic avascular plane anterior to the surface of the inferior vena cava. A tape is then passed through and the liver is resected under suspension., Methods: Cadaveric specimens were used to identify the structural relationship of the avascular plane and also to determine whether it is truly avascular., Results: Thirteen cases were analysed. The mean length of the avascular tunnel was 6.4 +/- 1.0 cm. The median number of accessory hepatic veins within the tunnel was two (zero to three). At the caudal half of the tunnel, the median number of veins was two (zero to three). As for the cranial half of the tunnel, there were two cases with one vein in each., Conclusions: The key to the liver hanging manoeuvre is to develop the retrohepatic tunnel. However, our study showed that it is not absolutely avascular. During the blind dissection, there is a chance of damaging a retrohepatic vein. This may result in troublesome haemorrhage within the confines of the tunnel. Video-assisted dissection of this region may help in visualisation, and hence control, in order to avoid bleeding.