[A case of von Hippel-Lindau syndrome with optic disc pit and macular hole].

A 69-year-old female patient presented to the ophthalmology department with complaints of blurred vision in the left eye for more than 10 days. Her medical history revealed a history of right renal tumor and left pheochromocytoma, which were treated with surgical resection at an external institution. Ophthalmic examination revealed a temporal superior cup-shaped optic disc pit in the left eye, along with a macular hole approximately 1/5 the size of the optic disc diameter in the macular region. Additionally, peripheral retinal examination at the 6 o'clock and 11 o'clock positions showed vascular tumors, each approximately 1.5 times the size of the optic disc diameter. Based on the patient's medical history, fundus findings, and auxiliary examination results, a diagnosis of macular hole in the left eye, optic disc pit in the left eye, and Von Hippel-Lindau (VHL) syndrome was established. Subsequently, the patient underwent left vitrectomy and macular hole repair surgery, leading to an improvement in visual acuity.

Qiliqiangxin capsule improves cardiac remodeling in rats with DOCA-salt-induced diastolic dysfunction.

OBJECTIVE: The aim of this study was to investigate the protective effect and mechanism of action (MOA) of Qiliqiangxin capsule (QL) in the deoxycorticosterone acetate (DOCA) salt-induced rat heart failure with preserved ejection fraction (HFpEF) model. MATERIALS AND METHODS: Nono-nephrectomy sixty Sprague Dawley (SD) rats received DOCA salt injection and 1% saline in drinking water for 4 weeks and were randomly divided into four groups on average: Model group (n=15), Sac/Val group (Sacubitril Valsartan 0.02 g/kg, n=15), QL-L group (Qiliqiangxin 0.25 g/kg, n=15) and QL-H group (Qiliqiangxin 1 g/kg, n=15). Another Normal group was set (n=15). Blood pressure, N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac index, echocardiography, and hemodynamics were measured to evaluate heart function. Masson and Wheat germ agglutinin (WGA) staining was performed to observe the fibrosis deposition and the cross-sectional area (CSA) of cardiomyocytes. The concentration levels of the serum cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and IL-10 inflammatory factors, were detected by ELISA; matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), transforming growth factor-ß1 (TGF-ß1), nuclear factor-κB (NF-κB), Smad homologue 2 (Smad2) and Smad homologue 3 (Smad3) expression were detected by Western-blot. RESULTS: Compared with the Model group, QL treatment significantly ameliorated the heart function in DOCA salt-induced rat HFpEF model, showing a decrease in cardiac index, an increase of the EF and E/A ratio, a reduction in the left ventricular anterior/posterior wall (LVAW/LVPW), in the time contraction of isovolumic diastolic time (IVRT), -dP/dt Max, and Tau, and the decrease of serum NT-ProBNP. Masson and WGA staining indicated that QL inhibited the fibrosis deposition and the myocardial hypertrophy compared with the Model group, which was consistent in reducing the protein expression levels of cardiac remodeling such as TGF-ß1, MMP2, MMP9, Smad2, and Smad3. Moreover, QL treatment inhibited the expression of NF-κB in the heart tissues and decreased the serum concentration of pro-inflammatory cytokines TNF-α and IL-2, instead, increasing the IL-10 concentration. CONCLUSIONS: QL improved the cardiac function and inhibited the myocardial fibrosis in DOCA salt-induced rat HFpEF by improving diastolic dysfunction, preventing left ventricular hypertrophy, and ameliorating the inflammatory responses model in DOCA salt-induced rat HFpEF model.

[Analysis of the efficacy of transnasal endoscopic annulus of zinn area decompression in the treatment of dysthyroid optic neuropathy].

Objective: To evaluate the early efficacy and safety of transnasal endoscopic decompression in the annulus of zinn (AZ) region for refractory dysthyroid optic neuropathy (DON) and to preliminarily analyze the correlated factors of postoperative visual function outcome. Methods: From July 2021 to January 2023, 35 patients (56 eyes) with DON who received AZ area decompression in Peking University Third Hospital were included retrospectively, including 9 males (13 eyes) and 26 females (43 eyes), aging (52.2±12.0) years. Among them, 35 eyes underwent two-wall (medial and inferior) orbital decompression using an endonasal endoscopic approach, while 21 eyes received three-wall (medial, lateral, and inferior) orbital decompression through a combined approach. Key parameters such as best corrected visual acuity (BCVA), visual field (MD value), eyeball prominence, intraocular pressure, and complications were recorded. Postoperative data were collected one month after surgery. The statistical analysis was performed using paired t-test and Spearman correlation analysis. Results: Significant outcomes were observed post surgery in BCVA, visual field, intraocular pressure and proptosis (t value was 8.37, 6.17, 4.50, and 9.20, respectively, all P<0.001). The reduction in proptosis was statistically significant between the 2-wall and 3-wall orbital decompression groups (t=-2.82, P=0.007). Changes in BCVA, visual field, and intraocular pressure before and after surgery was greater in the 3-wall orbital decompression group compared to 2-wall orbital decompression group, although the difference was not statistically significant (all P>0.05). Change in postoperative visual acuity and visual field was significantly positively correlated with preoperative visual acuity and preoperative visual field (all P<0.001). Similarly, change in intraocular pressure and proptosis was positively correlated with preoperative intraocular pressure and preoperative protrusion (all P<0.001). Preoperative diplopia was reported in seven patients (20.0%), and two new cases (5.7%) were noted post-operation, which resolved within 3 months after surgery. Conclusions: Endoscopic endonasal decompression of the AZ area is a safe and effective surgical treatment for DON, with notable improvements in BCVA. Furthermore, three-orbital wall decompression seems to yield better outcomes in terms of eye retraction.

[Research progress in non-coding RNAs in mediating immune responses of macrophages to Mycobacterium tuberculosis infection].

Tuberculosis (TB) is a chronic infectious disease caused by mycobacterium tuberculosis (MTB) infection. Macrophages are the first line in defensing MTB infection and the main host cells for the growth and persistence of MTB. Changes in macrophage function are critical for the host response to tuberculosis. Non-coding RNAs are involved in the pathophysiological process of many diseases, including TB, and play a very important regulatory role in the macrophage mediated immune response process. Therefore, we reviewed the mechanisms of the non-coding RNAs mediated function alteration of macrophages, in order to facilitate identification of potential therapeutic targets for host-directed anti-TB treatment.

[The clinical value of further accurate staging of pT2 gastric cancer based on the depth of invasion].

Objective: To investigate the clinical value of pT2 gastric cancer staging pT2a and pT2b according to the depth of muscularis propria invasion in evaluating the prognosis of gastric cancer. Methods: According to the 8th edition of TNM staging system for gastric cancer proposed by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), patients with gastric cancer who underwent radical surgery in the Fourth Hospital of Hebei Medical University from January 1, 2008 to January 1, 2015 were selected and divided into pT2a and pT2b stage group according to the depth of tumor invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Results: The median follow-up time of 1 411 patients with postoperative pathological pT2 stage was 68.8 months, and 1 347 patients (95.46%) received complete follow-up data. The 5-year OS rate was 65.85%, and the 5-year DFS rate was 67.83 %. The 5-year OS rate and 5-year DFS rate of 709 pT2a patients were 72.50% and 73.91%, respectively. The 5-year OS rate and 5-year DFS rate of 638 pT2b patients were 58.46% and 61.13%, respectively, significantly different from those of the pT2a group (P<0.001). Hierarchical analysis was performed according to N staging. The 5-year OS rates of pT2aN0M0 (274 cases), pT2aN1M0 (192 cases), pT2aN2M0 (147 cases), pT2aN3aM0 (59 cases) and pT2aN3bM0 (37 cases) were 83.58 %, 72.40 %, 68.71 %, 54.24 % and 35.12 %, respectively. The 5-year DFS rates were 84.67 %, 77.08 %, 67.35 %, 54.24 % and 35.14 %, respectively. In the pT2b group, the 5-year OS rates of pT2bN0M0 (209 cases), pT2bN1M0 (166 cases), pT2bN2M0 (127 cases), pT2bN3aM0 (78 cases) and pT2bN3bM0 (58 cases) were 76.08%, 62.05%, 56.69%, 37.18% and 17.24%, respectively, and the 5-year DFS rates were 80.86%, 69.28%, 54.33%, 35.90% and 15.52%, respectively. Under the same N stage, the OS rates of patients in the pT2a group were better than those in the pT2b group (P values were 0.023, 0.034, 0.034, 0.043 and 0.018, respectively). When the N stage was N0 and N1, there was no significant difference in the 5-year DFS rate between the pT2a group and the pT2b group (P values were 0.199 and 0.090, respectively). When the N stages were N2, N3a and N3b, the difference between the pT2a stage group and the pT2b stage group was statistically significant (P values were 0.027, 0.022 and 0.025, respectively). Conclusions: In the 8th edition of AJCC/UICC gastric cancer staging system, pT2 stage can be divided into pT2a stage (invasion of superficial muscularis) and pT2b stage (invasion of deep muscularis) according to the infiltration depth of muscularis propria. There are significant differences in prognosis between the two groups. Combined with the number of lymph node metastasis, the prognosis of patients with pT2 gastric cancer can be more accurately evaluated.

[The effect of cancer nodules on survival prognosis of gastric cancer patients].

Objective: To explore the relationship between cancer nodules and clinicopathological characteristics of gastric cancer, and analyze its impact on survival prognosis of gastric cancer patients. Methods: A retrospective analysis of 2 386 patients with gastric cancer who underwent radical surgery from January 1, 2012 to January 1, 2015 in the Third Surgery Department of the Fourth Hospital of Hebei Medical University was performed. The relationship between cancer nodules and clinicopathological characteristics of gastric cancer and its impact on survival prognosis of gastric cancer patients were analyzed. Results: Among the 2 386 patients, there were 459 cases (19.24%) with cancer nodules, and 1 927 cases (80.76%) without cancer nodules. Logistic multivariate analysis showed that pT staging (P=0.036), pN staging (P=0.024), pTNM staging (P=0.032), Borrmann classification (P=0.008), vascular tumor thrombus (P=0.001) were independent risk factors for cancer nodules. The complete follow-up date of 2 273 cases (95.26%) of 2 386 patients with gastric cancer were obtained. A total of 1 259 patients relapsed and 1 152 died during the follow-up period. The 5-years overall survival (OS) rate was 49.32%, and the 5-years disease-free survival (DFS) rate was 44.61%. Among them, the 5-years OS rate and DFS rate of those with cancer nodules were 26.76% and 24.94%, while the 5-years OS rate and DFS rate of those without cancer nodules were 54.75% and 49.34%, respectively (P<0.001). Patients with positive cancer nodules were divided into 3 groups according to the number of cancer nodules: 1 (115 cases), 2 to 3 (202 cases), and more than 4 (124 cases). The 5-years OS rates of 3 groups were 41.74%, 30.69% and 10.48%, respectively (P<0.001). The 5-years DFS rates were 40.00%, 28.22% and 9.68%, respectively (P<0.001). Cox multivariate analysis showed that histological type (P=0.004), pT staging (P=0.007), pN staging (P=0.004), pTNM staging (P=0.002), vascular tumor thrombus (P=0.034), cancer nodules (P=0.005) and the number of cancer nodules (P=0.001) were independent risk factors for the prognosis of gastric cancer patients, and postoperative adjuvant chemotherapy (P=0.043) was a protective factor for the prognosis of gastric cancer patients. Conclusion: Cancer nodules are closely related to the tumor stage and prognosis of gastric cancer patients. The number of cancerous nodules is an independent risk factor for the prognosis of gastric cancer patients.

[Clinicopathological characteristics of NTRK-rearranged mesenchymal tumors in childhood].

Objective: To investigate the clinical and pathological features of pediatric NTRK-rearranged tumors. Methods: Four NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children's Medical Center, Shanghai Jiaotong University and Singapore KK Women's and Children's Hospital from January 2017 to September 2019 were identified. Pan-TRK immunohistochemistry, and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations (FISH) were performed. NTRK gene rearrangement was detected using sequencing-based methods. Results: There were 3 males and 2 females in this study. The patients were between 3 months and 13 years of age. Histologically, the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells. Immunohistochemistry showed positive reactivity for pan-TRK in all tumors, with nuclear staining for NTRK3 fusion, and cytoplasmic staining for NTRK1 fusion. The molecular testing revealed NTRK gene fusions (one each of TPM3-NTRK1, ETV6-NTRK3 and DCTN1-NTRK1, and two cases of LMNA-NTRK1). Two patients were receiving larotrectinib. The others were are well without disease, with follow-up durations of 9 to 29 months. Conclusions: NTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified. A novel DCTN1-NTRK1 fusion is described. Pan-TRK immunohistochemistry is useful for diagnosis. NTRK-targeted therapy may be an option for unresectable, recurrent or metastatic cases.

[Pathological characteristics and survival analysis of 355 patients with gastroenteropancreatic neuroendocrine neoplasms].

Objective: Biological behavior, pathological characteristics and prognostic factors of 355 cases with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) were analyzed in this retrospective study. Methods: In our study, 355 patients pathologically diagnosed as GEP-NENs were identified from April 2006 to November 2017 in the Fourth Hospital of Hebei Medical University. The biological behavior, pathological characteristics and prognosis were analyzed retrospectively. Results: There were 355 patients (228 males and 127 females) with a mean age of 58.3±10.7 years. GEP-NENs were detected most frequently in the stomach (48.2%), followed by the pancreas (16.1%), colorectum (14.1%), esophagus (7.6%), duodenum/jejunum(5.6%), liver (4.2%), appendix (2.3%) and gallbladder/bile duct (2.0%). The main clinical manifestations of non-functional GEP-NENs were abdominal pain (88/350, 25.14%), ventosity (77/350, 22.00%) and dysphagia (68/350, 19.43%), which were generally lacking specificity at the first diagnosis. 295 patients were treated surgically, including 45 cases of endoscopic resection and 250 cases of laparoscopic operation. Concerning to pathological grading, there were 22.5% (80/355) patients in grade 1 (G1), 12.7% (45/355) in grade 2 (G2), and 58.9% (209/355) in grade 3 (G3). The median follow-up time was 34 months. Furthermore, the 1-, 3- and 5-year overall survival calculated by Kaplan-Meier method were 80.1%, 59.8%, and 57.5%, respectively. Univariate analysis revealed that tumor site, treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis, tumor size, preoperative leukomonocyte level and preoperative plasma albumin were associated with overall survival (all P<0.05). Multivariate analysis showed that treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis and tumor size were independent prognostic factors for GEP-NENs (all P<0.05). Conclusions: The clinicopathological characteristics of GEP-NENs should be mastered by clinicians, and the standard treatment measures were also needed to be formulated based on the prognostic factors in order to improve the prognosis of patients.

[Application of the pathological classification of "CCCG-WT-2016" (2019 revision) for treatment of Wilms tumors].

Objective: To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors. Methods: Ninety-one cases of Wilms tumor diagnosed at Shanghai Children's Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016." Results: The specimens were obtained by core biopsy (n=21), primary nephrectomy (n=41), post-chemotherapy nephrectomy/resection (n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) (n=11). The specimens of core biopsy and primary nephrectomy (n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk (n=0), intermediate risk (n=10) and high risk (n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk (n=0), intermediate risk (n=5) and high risk (n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions: The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.

LncRNA SNHG1 contributes to tumorigenesis and mechanism by targeting miR-338-3p to regulate PLK4 in human neuroblastoma.

OBJECTIVE: Neuroblastoma is a common malignancy in children. Despite the occurrence of diverse therapies in recent years, the survival rate of patients with high-risk NB is still unpredictable due to the high metastatic potential and poor prognosis. Therefore, it is urgent to study the molecular mechanism of NB metastasis. SNHG1 has been reported to be closely related to the development, metastasis, and prognosis of many cancers. The purpose of this study was to clarify the molecular mechanism of the role of SNHG1 in NB tumors. PATIENTS AND METHODS: The expression levels of SNHG1, miR-338-3p, and PLK4 were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The functional targets between miR-338-3p and SNHG1 or PLK4 were predicted by online software Diana tools and observed by Luciferase reporter assay and RIP assay. Cell proliferation was measured by MTT assay. Cell migration and invasion were operated through flow cytometry. The expression of p-AKT was quantified by Western blot. Xenograft tumor model was established to confirm the biological role of SNHG1 in NB in vivo. RESULTS: The expression levels of SNHG1 and PLK4 were increased in NB tissues and cells, and miR-338-3p expression was on the contrary. PLK4 was verified as a direct target of miR-338-3p and miR-338-3p could specially bind to SNHG1. The negative effect of SNHG1 down-regulation on cell proliferation, migration, and invasion could be rescued by miR-338-3p inhibition. The suppression of miR-338-3p mimics on cell proliferation, migration, and invasion could be reversed by PLK4 overexpression. In addition, SNHG1 knockdown weakened the volume and weight of tumor in vivo. CONCLUSIONS: SNHG1 conduced to tumorigenesis and mechanism by upregulating PLK4 and by acting as miR-338-3p sponge in neuroblastoma.

[High definition MRI rectal lymph node aided diagnostic system based on deep neural network].

Objective: To investigate the clinical significance of high definition (HD) MRI rectal lymph node aided diagnostic system based on deep neural network. Methods: The research selected 301 patients with rectal cancer who underwent pelvic HD MRI and reported pelvic lymph node metastasis from July 2016 to December 2017 in Affiliated Hospital of Qingdao University. According to the chronological order, the first 201 cases were used as learning group. The remaining 100 cases were used as verification group. There were 149 males (74.1%) and 52 females in the study group, with an average age of 58.8 years. There were 76 males (76.0%) and 24 females in the validation group, with an average age of 60.2 years. Firstly, Using deep learning technique, researchers trained the 12 060 HD MRI lymph nodes images data of learning group with convolution neural network to simulate the judgment process of radiologists, and established an artificial intelligence automatic recognition system for metastatic lymph nodes of rectal cancer. Then, 6 030 images of the validation group were clinically validated. Artificial intelligence and radiologists simultaneously diagnosed all cases of HD MRI images and made the diagnosis results of metastatic lymph node. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to compare the diagnostic level of them. Results: After continuous iteration training of the learning group data, the loss function value of artificial intelligence decreased continuously, and the diagnostic error decreased continuously. Among the 6 030 images of verification group, 912 images were considered to exist metastatic lymph nodes in radiologists' diagnosis and 987 in artificial intelligence diagnosis. There were 772 images having identical diagnostic results of lymph node location and number of metastases with the two methods. Compared with manual diagnosis, the AUC of the intelligent platform was 0.886 2, the diagnostic time of a single case was 10 s, but the average diagnostic time of doctors was 600 s. Conclusion: The HD MRI lymph node automatic recognition system based on deep neural network has high accuracy and high efficiency, and has the clinical significance of auxiliary diagnosis.

KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression.

Gastric cancer (GC) is a leading cause of global cancer-related death. The incidence and mortality rates of gastric cancer in China are second and third ranked in all forms of malignant tumors. Krüppel-like factor11 (KLF11) is a member of the KLF family, and previous studies have shown it significantly influences epithelial ovarian, pancreatic and liver cancer proliferation, differentiation and apoptosis. However, the expression and some biological functions of KLF11 in GC are still unclear. We therefore collected and analyzed the mRNA and protein expressions of KLF11 in 59 paired gastric cancer tissues and matched healthy gastric tissue samples. We then investigated the KLF 11 biological functions and potential mechanisms in BGC823 and HGC27 gastric cancer cell lines. Analysis of KLF11 in gastric cancer specimens confirmed up-regulation compared to adjacent healthy gastric tissues, and similar results were evident in the GC cell lines. Ectopic expression of KLF11 was significantly associated with GC cell invasion and migration. KLF11 functions were most effective in Twist1 expression and knockdown, and also in KLF11 up-regulation which was accompanied by corresponding change in Twist1 expression; but these effects were inhibited when KLF11 was silenced by the small interfering RNA (siRNA). The relative Twist1 promoter region activity increased gradually with increasing KLF11 plasma, and KLF11 therefore has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression. Finally, the results of this study should improve understanding of the KLF11 and EMT regulating network and KLF11's use as a potential therapeutic target in gastric cancer.

[Changes and differences of DNA methylation in human macrophages infected with virulent and avirulent Mycobacterium tuberculosis].

Objective: To profile DNA methylation and compare differentially methylated region (DMR) of macrophages infected with virulent and avirulent strains of Mycobacterium tuberculosis (MTB). Methods: PMA(50 ng/ml) treated THP-1 macrophages were left uninfected or infected with the virulent H37Rv(THP-1/Rv) or avirulent H37Ra(THP-1/Ra). The genomic DNA was then extracted and DNA methylation was profiled via Reduced Representation Bisulfite Sequencing (RRBS). The DNA methylation pattern and DMRs between the tested samples were indentified. DMRs-associated genes were annotated, clustered by Gene Ontology (GO), and the pathways analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). mRNA expression of several DMR-associated genes were verified by Q-PCR, and Student's t-test was used to analyze the differential expression between either 2 samples. Results: The mostly DNA methylated C in 3 samples was in CG, accounting for 98% of all types of methylated C(CG, CGH, CHH). Besides, the average DNA methylation level in THP-1/Rv, THP-1/Ra and THP-1/NC were 7.72%, 7.38% and 7.58% in the promoter, and 9.90%, 9.57% and 9.80% in the CpG island (CGI), respectively. We identified 58 DMRs between H37Rv and H37Ra infected THP-1 macrophages with an average length of 152 bp. Six DMRs-associated genes were enriched. Among them, AP-1 and DDIT4 were differentially expressed in cells infected with H37Rv and H37Ra. Conclusions: Infection with MTB is not correlated with a large-scale gain or loss in DNA methylation in host cells. AP-1 and DDIT4 might be novel virulence-related genes regulated by DNA methylation of their corresponding promoter regions.

[Modified capsular arthroplasty for young patients with developmental dislocation of the hip].

Developmental dislocation of the hip(DDH) is one of the most serious hip diseases. Patients with unilateral DDH are prone to secondary osteoarthritis, low back pain, gait disturbance and compensatory scoliosis because of the leg length discrepancy. Total hip arthroplasty(THA) is the highly effective treatment for patients with hip pain or dysfunction caused by unilateral DDH, thus decrease the demand for hip-preserving surgeries such as capsular arthroplasty which may postpone or avoid hip replacement. However, the failure rate of THA for young patients is high and the majority of young patients may require one or more revision arthroplasties throughout their lifetime. The basic principle of capsular arthroplasty is that the femoral head wrapped by capsule is placed into a newly reamed socket on the location of true acetabulum. Therefore, hip replacement for patients with previous capsular arthroplasty becomes easier and safer than primary THA. However, the early capsular arthroplasty have been abandoned due to the relatively high rates of femoral head necrosis and hip stiffness. Ganz modified the early procedure with the technique of surgical hip dislocation in 2012, and emphasized the importance of postoperative rehabilitation. The incidence of complication, therefore, decreased greatly due to the preservation of main blood supply of femoral head as well as the proper postoperative management. In order to improve the clinical outcomes of this modified procedure, the selection of indications and surgeons' experience should also be taken into consideration.

[DNA damage associated genetic variants contribute to lung cancer susceptibility in a Han Chinese population].

OBJECTIVE: To explore the association between DNA damage-related genetic variants and lung cancer susceptibility in a Han Chinese population. METHODS: This case-control study enrolled patients from the Cancer Hospital of Jiangsu Province and Jiangsu Province Hospital from 2003 to 2009. Controls were randomly selected from individuals who visited the same hospital or a community-based health examination program during the same time period. A 5 ml venous blood sample was obtained from each participant and epidemiological information was collected on a standard questionnaire. Illumina Infinium(®) BeadChip was used for genotyping of 35 DNA damage-related single nucleotide variations (SNVs), which were identified in our previous study. Multivariate and binary logistic regressions were used to calculate the OR and 95%CI for lung cancer risk. HaploReg V4.1 and Regulome DB were used to understand functional annotation on important SNV. RESULTS: The distributions of age (61.06±10.15) vs. (61.32±11.07) years; t=-0.72, P=0.473) and sex (χ(2)=1.81, P=0.179) were similar between cases and controls. However, the case group had a higher frequency of smokers (61.08% vs. 48.54%; χ(2)=50.04, P<0.001) and heavy smokers (42.28% vs. 24.07%; χ(2)=122.32, P<0.001). Among the 34 SNVs that passed quality control, two SNVs were significantly associated with lung cancer risk after adjustments for age, sex and cumulative smoking dose: rs9267576 C>A (CA genotype/CC genotype, OR=1.56, 95% CI: 1.01-2.40) and rs3130683 A>G (AG genotype/AA genotype, OR=1.87, 95%CI: 1.13-3.09). After step-wise logistic regression analysis, only the rs3130683 SNV was retained in the model, indicating that the association between rs9267576 and lung cancer may be due to the effect of rs3130683. Functional annotation indicated that rs3130683 was located in the promoter and enhancer regions, and was an expression quantitative trait loci of HLA. The Cancer Genome Atlas indicated that expression of HLA-C, DQB1, DRB1 and DRB5 in lung cancer tissue was significantly lower than in paired normal tumor-adjacent tissue, with down-regulation of the four respective genes in 81.3%, 88.8%, 90.7% and 90.7% of lung cancer tissues (P-values were 6.68×10(-15), 2.21×10(-13), 2.20×10(-16), 2.58×10(-13), respectively). CONCLUSIONS: The SNV rs3130683 (A>G) was associated with the risk of lung cancer in a Han Chinese population. This SNV may affect the risk of lung cancer by regulating HLA expression.

Modified cytospin slide microscopy method for rapid diagnosis of smear-negative pulmonary tuberculosis.

OBJECTIVE: To evaluate a modified method of the Ziehl-Neelsen stain and determine whether it improves the detection rate of acid-fast bacilli (AFB) in bronchoalveolar lavage fluid (BALF) specimens. DESIGN: Bronchoscopy of patients with suspected smear-negative pulmonary tuberculosis (PTB) patients was conducted to collect BALF to assess the efficacy and accuracy of the modified method for PTB diagnosis. RESULTS: A total of 106 BALF specimens was collected from 74 PTB patients on the basis of BALF samples that were culture-positive for Mycobacterium tuberculosis. When analysed by patient, the sensitivity and specificity of our modified method were respectively 87.8% and 99.6%, while the positive predictive (PPV) and negative predictive values (NPV) were respectively 98.5% and 96.8%. Conversely, the sensitivity of direct smears and concentrated smears was respectively 16.2% and 37.8%, with 100% specificity. On analysing 106 samples, the culture positivity rate of the direct smear and the concentrated smear methods was respectively 76.4%, 13.2% and 34%, while it was 91.5% for the modified method. CONCLUSION: The sensitivity of our modified method was significantly higher than that of direct or concentrated smears. Overall, the modified method improved the detection rate of AFB in BALF specimens, and provided an efficient and accurate diagnosis of PTB in patients with suspected smear-negative PTB.

Monopole excitations of a harmonically trapped one-dimensional Bose gas from the ideal gas to the Tonks-Girardeau regime.

Using a time-dependent modified nonlinear Schrödinger equation (MNLSE)-where the conventional chemical potential proportional to the density is replaced by the one inferred from Lieb-Liniger's exact solution-we study frequencies of the collective monopole excitations of a one-dimensional Bose gas. We find that our method accurately reproduces the results of a recent experimental study [E. Haller et al., Science 325, 1224 (2009)] in the full spectrum of interaction regimes from the ideal gas, through the mean-field regime, through the mean-field Thomas-Fermi regime, all the way to the Tonks-Giradeau gas. While the former two are accessible by the standard time-dependent NLSE and inaccessible by the time-dependent local density approximation, the situation reverses in the latter case. However, the MNLSE is shown to treat all these regimes within a single numerical method.

Annexin A2 is implicated in multi-drug-resistance in gastric cancer through p38MAPK and AKT pathway.

Studies have shown that Annexin A2 (ANXA2) is related with tumor proliferation, apoptosis, differentiation, invasion, migration, and drug resistance. The purpose of this study was to investigate the role and its mechanisms of ANXA2 in multi-drug-resistance (MDR) in gastric cancer. ANXA2 expression in both gastric cancer tissues and cell lines were detected by quantitative real-time PCR (RT-qPCR) and Western blotting. The cell proliferation was measured by SRB assay. The pool of siRNA against ANXA2 was designed and synthesized and then transfected into resistant gastric cancer SGC7901/DDP cells. ANXA2 expression was detected by RT-qPCR and Western blotting. Drug sensitivities of SGC7901/DDP cells to P-gp-related drug (doxorubicin) and P-gp-non-related drugs (5-FU and cisplatin) were measured by SRB assay. Expression of MDR-related genes and phosphorylation of AKT and MAPKs were also detected by RT-qPCR and Western blotting. Results showed that ANXA2 expression was significantly higher in gastric specimens than that in normal tissues, and negatively correlated with the differentiation level of gastric cancer. In addition, ANXA2 expression level was higher in SGC7901/DDP cells than that in parent SGC7901 cells. After knock-down ANXA2 expression using ANXA2 small interfering RNA, the drug sensitivity of SGC7901/DDP cells to doxorubicin, 5-FU and DDP increased. Delivery of ANXA2 siRNA significantly downregulated the expression of P-gp, MRP1 and Bcl-2, while markedly upregulated Bax in SGC7901/DDP cells. However, several other MDR factors such as GST-π, TOPO-I and TOPO-II had no obvious changes. Additionally, phosphorylation of P38MAPK and AKT, but not ERK1/2 or JNKs was specifically decreased in SGC7901/DDP cells after ANXA2 siRNA delivery. Importantly, P38MAPK and AKT inhibitor increased the drug sensitivity of SGC701/DDP cells in a similar way as ANXA2 siRNAs does. ANXA2 is involved in gastric cancer MDR through regulating p38MAPK and AKT pathways as well as certain MDR factors.