A bibliometric study on trends in chiropractic research from 1920 to 2023.

OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.

Characterization and Comparison Analysis of WHO Monographs on Selected Medicinal Plants and ISO Standards of Chinese Materia Medica.

Medicinal plants or Chinese materia medica (CMM) are now attracting worldwide attention as they have increasingly prominent advantages over chemical drugs in disease treatment and healthcare. Since the 1990s, World Health Organization (WHO) and International Organization for Standardization established the Technical Committee of Traditional Chinese Medicine (ISO/TC 249) have carried out the development of quality standards on medicinal plants or CMMs respectively, and a considerable number of monographs and international standards have been published. Since the two international organizations adhere to different principles, the standards they develop naturally have different emphasis. Driven by market demand and international trade, ISO mainly takes quality, efficacy and safety into consideration when developing standards, while WHO pays more attention to clinical practice, quality control and medication guidance. Up to now, there is a lack of comparative analysis on the records, background, principles, basic content, and main requirements of quality standards on medicinal plants or CMMs respectively published by WHO and ISO. Therefore, based on international standards of CMM developed by ISO/TC 249 platform and WHO Monographs on Selected Medicinal Plants, this paper systematically compares the purposes, selected principles, standard-developing process, basic content, and main quality requirements to summarize their similarities and differences, and find their merits, aiming to serve as a reference to the development of international standards for CMMs that helps them go global.

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

[Effect of oblique needling at Ashi-point on expression of MyoD1/Pax7 in mice with quadriceps femoris injury].

OBJECTIVE: To observe the effect of oblique needling at Ashi-point on behavior, and cell morphology, myogenic differentiation antigen (MyoD1) and paired box transcription factor Pax7 (Pax7) of quadriceps femoris tissue in quadriceps femoris injured mice. METHODS: A total of 24 C57BL/6 male mice were randomly divided into control, model, shallow insertion and deep insertion groups, with 6 mice in each group. The quadriceps femoris injury model was established by single intramuscular injection of 0.5% bupivacaine (BPVC). Twenty-four hours after modeling, mice of the two acupuncture groups were received oblique needling on the surface or through the muscle belly of quadriceps femoris for once, the oblique needling was lifted and inserted 3 times. The climbing pole test was conducted 24 h after modeling and 24 h after EA. Histopathological changes of quadriceps femoris was observed by H.E. staining. The expressions of MyoD1 and Pax7 were detected by immunohistochemistry. RESULTS: Compared with the control group, the score of climbing pole test was lower (P<0.01), and the expressions of MyoD1 and Pax7 significantly increased (P<0.01) in the model group. After the intervention and compared with the model group, the score of climbing pole test was higher (P<0.01), and the expressions of MyoD1 and Pax7 obviously increased (P<0.01) in the two acupuncture groups. The therapeutic effect of deep insertion group was apparently superior to that of shallow insertion group in up-regulating the climbing pole test score and expressions of MyoD1 and Pax7 (P<0.05, P<0.01). H.E. stain showed large areas of inflammatory infiltration, muscle cells swelling, atrophy, rupture, degeneration and necrosis, different cell sizes and morphologies, enlarged intervals, nuclear aggregation, deep nuclear staining, nuclear pyknosis, and hemorrhage in the model group, which was relatively milder in both needling groups. CONCLUSION: Oblique needling at Ashi-point can effectively promote the benign repair of injured quadriceps muscle and promote the recovery of exercise ability in mice, which may be associated with its effect in up-regulating the expression of MyoD1 and Pax7 protein. The role of deep insertion is superior to that of shallow insertion.

Value of neutrophil-to-lymphocyte ratio as a marker of renal damage in patients with H-type hypertension.

Aim: To explore the relationship between the neutrophil-to-lymphocyte ratio (NLR) and renal damage in patients with H-type hypertension. Materials & methods: A total of 618 patients between 2017 and 2019 were analyzed retrospectively. Results: NLR was significantly correlated with renal damage in hypertension patients. Appropriate cut-off value for NLR (2.247) was determined by receiver operating characteristic curve; linear regression analysis showed that NLR and estimated glomerular filtration rate, blood urea nitrogen/creatinine has a significant negative correlation in H-type hypertension group (p < 0.05); logistic regression analysis showed that the risk of renal damage increased by 10% for each 1 umol/l increase of homocysteine, and 51% for each 1.0 increase of NLR in H-type hypertension patients. Conclusion: NLR worth popularizing in prediction of renal damage in patients with H-type hypertension.

Aberrant resting-state cerebral blood flow and its connectivity in primary dysmenorrhea on arterial spin labeling MRI.

PURPOSE: This study aimed to clarify the resting-state cerebral blood flow alteration patterns induced by primary dysmenorrhea, investigate the relationships between cerebral blood flow alterations and clinical parameters of patients with primary dysmenorrhea, and explore whether brain regions with abnormal cerebral blood flow also feature functional connectivity changes. METHODS: Arterial spin labeling imaging and clinical parameters were acquired in 42 patients with primary dysmenorrhea and 41 healthy controls during their menstrual phases. Differences in cerebral blood flow were compared between the two groups, and the clusters with significant group differences were selected as the regions of interest for further statistical analyses. RESULTS: Compared to healthy controls, patients with primary dysmenorrhea exhibited increased cerebral blood flow in the bilateral precuneus, left posterior cingulate cortex, and right rolandic operculum. Among patients with primary dysmenorrhea, we identified a negative correlation between the cerebral blood flow in the right rolandic operculum and the visual analogue score for anxiety, and greater correlation between the functional connectivity in the precuneus/posterior cingulate cortex and the right middle cingulate cortex, and between the right rolandic operculum and the left inferior parietal lobule and the bilateral postcentral gyrus. DISCUSSION: Cerebral blood flow abnormalities associated with primary dysmenorrhea were mainly concentrated in the areas comprising the default mode network in primary dysmenorrhea patients, which could be involved in the central mechanism of primary dysmenorrhea. Cerebral blood flow alteration in the rolandic operculum may underlie an anxiety-induced compulsive tendency in patients with primary dysmenorrhea. Investigating the enhanced connectivity among various pain-related brain regions could improve understanding of the onset and development of primary dysmenorrhea.

[Comparison of therapeutic effect of soft-tissue relaxing needling and electroacupuncture for knee osteoarthritis].

OBJECTIVE: To compare the clinical efficacy of soft-tissue relaxing needling and electroacupuncture (EA) in the treatment of knee osteoarthritis (KOA), so as to explore a new and more effective therapy for KOA. METHODS: Forty patients with KOA who met our diagnostic criteria were randomly and equally divided into acupuncture group and soft-tissue relaxing needling (relaxing-needling) group. EA (20 Hz, a tolerable strength and duration of 20 min) was applied to the unilateral Neixiyan(EX-LE5) and Waixiyan(EX-LE5), and manual acupuncture stimulation was applied to Heding(EX-LE2), Xuehai (SP10), Xiyangguan (GB33), Liangqiu(ST34), Yanglingquan(GB34) and Yinlingquan(SP9) on the affected side by using uniform reinforcing-reducing technique. In the relaxing-needling group, after identifying the tender point and nodule-like or stiff-strip-muscle spot at the affected limb by palpation, we used filiform needles to insert into them, then, made a longitudinal separation or point-like pricking. The visual analog scale (VAS) pain score, knee flexion activity (range of motion, ROM), and the knee osteoarthritis severity (Lequesne index, composed of daily living, walking distance and pain) were measured before and after the treatment. The therapeutic effect was assessed by consulting the Guiding Principles for Researching New Drugs of Traditional Chinese Medicine (2002) and Criteria for Diagnosis and Assessment of Therapeutic Effect of Syndromes or Illnesses of Traditional Chinese Medicine (1994). RESULTS: After the treatment, the VAS score and Lequesne index were significantly decreased in both acupuncture and relaxing-needling groups (P<0.001), and the ROM score was considerably increased in both groups in comparison with their own pre-treatment (P<0.001). The difference values of VAS score and Lequesne index between pre- and post-treatment were significantly higher in the relaxing-needling group than in the acupuncture group (P<0.05). Of the two 20 cases in the relaxing-needling and acupuncture groups, 8 and 3 experienced a remarkable improvement in their symptoms, 10 and 13 were effective, 2 and 4 failed, with the effective rate being 90.0% and 80.0%, respectively. No significant difference was found between the two groups in the difference value of ROM score and the effective rate (P>0.05)．. CONCLUSION: Both relaxing-needling and EA therapies are comparable in the therapeutic effect for KOA, and the former is superior to the latter in reducing the joint pain and improving the knee joint locomotor function, thus being worthy of clinical application.

Altered amplitude of low-frequency fluctuation and regional cerebral blood flow in females with primary dysmenorrhea: a resting-state fMRI and arterial spin labeling study.

Purpose: The current study aimed to explore the central mechanism of primary dysmenorrhea (PD) by investigating the alterations in resting state amplitude of low-frequency fluctuation (ALFF) and regional cerebral blood flow (CBF) between PD patients and healthy controls (HCs). Patients and methods: A total of 34 female subjects including 20 PD patients and 14 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling technique (ASL) MRI during menstrual phase. Subsequently, the differences in ALFF and CBF were compared in the two groups. The visual analog scores for pain (VAS-P) and for anxiety (VAS-A) were applied to assess cramping pain and related symptoms in PD patients. Finally, Pearson's correlation analysis was performed to analyze relationships between the neuroimaging findings and clinical characteristics. Results: Compared to HCs, PD patients had decreased ALFF in the right cerebellum posterior lobe, right middle temporal gyrus, right parahippocampal gyrus, right hippocampus, right brainstem and left parietal lobe. In addition, elevated CBF values were observed in the right inferior frontal gyrus, right precentral gyrus, and right superior temporal gyrus. There was no significant correlation between ALFF, CBF values and clinical characteristics including onset age of dysmenorrhea, VAS-A, and VAS-P in PD patients. Conclusion: The preliminary alterations of ALFF and CBF values in PD patients were observed in different pain-related brain regions, which were involved in multiple dimensions of pain and pain modulation. The combination of rs-fMRI and ASL MRI might provide complementary information for a better understanding of the central mechanism in PD.

Predictive value of single-nucleotide polymorphism signature for recurrence in localised renal cell carcinoma: a retrospective analysis and multicentre validation study.

BACKGROUND: Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. METHODS: In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. FINDINGS: Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660-0·826] in region 1, 0·734 [0·651-0·814] in region 2, and 0·736 [0·649-0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81-10·07] in the internal testing set, 5·39 [3·38-8·59] in the independent validation set, and 4·62 [2·48-8·61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0·811 [95% CI 0·756-0·861]). INTERPRETATION: Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

Efficacy and safety of first-line sunitinib in Chinese patients with metastatic renal cell carcinoma.

AIM: We report the first prospective study of sunitinib for metastatic renal cell carcinoma (mRCC) in China. METHODS: Chinese mRCC patients received first-line sunitinib 50 mg daily (4/2 regimen). Overall survival (OS), progression-free survival (PFS), objective response rate and safety were assessed. Potential efficacy biomarkers were explored in post hoc analyses. RESULTS: Median PFS was 61.7 weeks; median OS was 133.4 weeks; objective response rate was 31.1%. Most frequent adverse events (AEs) were: hand-foot syndrome (63.8%), decreased white blood cell count (52.4%), fatigue (51.4%) and decreased platelet count (51.4%). AEs were identified that predicted longer PFS and OS. CONCLUSION: Sunitinib showed efficacy and manageable AE profile in treatment-naive Chinese mRCC patients. Larger prospective studies are required to confirm identified AEs as predictors of efficacy.

AHNAK2 is a Novel Prognostic Marker and Oncogenic Protein for Clear Cell Renal Cell Carcinoma.

Integrative database analysis was performed to identify novel candidate oncogene AHNAK2 overexpressed in clear cell renal cell carcinoma (ccRCC). However, the function of AHNAK2 in cancer cells is currently unknown. In this study, we first confirmed the upregulation of AHNAK2 in ccRCC tissues compared with adjacent normal tissues in 15 pairs of samples. Then we analyzed AHNAK2 expression in a large cohort of ccRCC patient samples (n = 355), and found that up-regulation of AHNAK2 was positively correlated with tumor progression and poor survival (p = 0.032). Knockdown of AHNAK2 inhibited cancer cell proliferation, colony formation and migration in vitro and tumorigenic ability in vivo. Meanwhile, knockdown of AHNAK2 impaired the cell oncologic-metabolism by inhibiting lipid synthesis. Moreover, we observed that expression of AHNAK2 was greatly upregulated, at least in part, by hypoxia in cancer cells. By using chromatin immune-precipitation (CHIP) and promoter-luciferase reporter assays, we identified that upregulation of AHNAK2 induced by hypoxia was hypoxia-inducible factor-1α (HIF1α)-dependent. Knockdown of AHNAK2 impaired hypoxia-induced epithelial-mesenchymal transition (EMT) and stem cell-like properties. Considered together, we reveal that AHNAK2 is upregulated in cancer cells and hypoxic upregulation of AHNAK2 can drive tumorigenesis and progression by supporting EMT and cancer cell stemness. Thus, AHNAK2 is a novel prognostic marker and an oncogenic protein for ccRCC.

A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy-A single-institution experience.

BACKGROUND: Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin-preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as "T1G3." OBJECTIVE: To evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18-70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. RESULT: Complete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). CONCLUSION: GC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

Peripheral monocyte count: an independent diagnostic and prognostic biomarker for prostate cancer - a large Chinese cohort study.

Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 × 109 l-1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen (PSA), free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival (hazard ratio = 2.244, P < 0.05) and overall survival (hazard ratio = 1.995, P < 0.05), but not progression-free survival (P = 0.117). Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.

Regulation of Prostate Development and Benign Prostatic Hyperplasia by Autocrine Cholinergic Signaling via Maintaining the Epithelial Progenitor Cells in Proliferating Status.

Regulation of prostate epithelial progenitor cells is important in prostate development and prostate diseases. Our previous study demonstrated a function of autocrine cholinergic signaling (ACS) in promoting prostate cancer growth and castration resistance. However, whether or not such ACS also plays a role in prostate development is unknown. Here, we report that ACS promoted the proliferation and inhibited the differentiation of prostate epithelial progenitor cells in organotypic cultures. These results were confirmed by ex vivo lineage tracing assays and in vivo renal capsule recombination assays. Moreover, we found that M3 cholinergic receptor (CHRM3) was upregulated in a large subset of benign prostatic hyperplasia (BPH) tissues compared with normal tissues. Activation of CHRM3 also promoted the proliferation of BPH cells. Together, our findings identify a role of ACS in maintaining prostate epithelial progenitor cells in the proliferating state, and blockade of ACS may have clinical implications for the management of BPH.

GFOD1 and peejar are promising markers for clear-cell renal cell carcinoma disease progression.

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy. The molecular pathogenesis of ccRCC remains unclear and biomarkers for daily practice were still limited. We performed an integrative analysis of two public ccRCC microarray datasets, E-GEOD-22541 and E-MTAB-1050, The candidate differential expression genes (DEG) were then confirmed in the E-GEOD-53757 dataset. In addition, an independent cohort of 50 ccRCC and 36 non-tumor kidney tissues were analyzed to examine the selected DGEs by qRT-PCR. We identified and validated two DEGs, namely GFOD1 and peejar, which were significantly up-regulated in ccRCC compared with normal renal tissues (p < 0.001). Moreover, the expression of these two genes are related to histological grade and stage and decrease of their expression correlated with disease progression (p < 0.05). Furthermore, we found the expression of peejar was positively correlated with the expression of GFOD1 in ccRCC tissue, with Pearson correlation coefficiency reaching 0.939 (p < 0.001). GFOD1 and peejar were novel genes correlated with ccRCC disease progression and patients' poor prognosis.

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis.

Previous studies have reported aberrant expression of the miR-183-96-182 cluster in a variety of tumors, which indicates its' diagnostic or prognostic value. However, a key characteristic of the miR-183-96-182 cluster is its varied expression levels, and pleomorphic functional roles in different tumors or under different conditions. In most tumor types, the cluster is highly expressed and promotes tumorigenesis, cancer progression and metastasis; yet tumor suppressive effects have also been reported in some tumors. In the present study, we discuss the upstream regulators and the downstream target genes of miR-183-96-182 cluster, and highlight the dysregulation and functional roles of this cluster in various tumor cells. Newer insights summarized in this review will help readers understand the different facets of the miR-183-96-182 cluster in cancer development and progression.

Microsurgical vasoepididymostomy for patients with infectious obstructive azoospermia: cause, outcome, and associated factors.

Azoospermia is of great importance to male infertility. Obstructive azoospermia (OA) due to infection is the most prevalent form of OA in China and has been less studied. We aim to observe the treatment outcome of microsurgical vasoepididymostomy (VE) and also to identify the factors relative to the result after reconstructive surgery. Two hundred and eight men presenting with OA due to infection during the study period from July 2010 to July 2013 were prospectively evaluated. Clinical examination, semen analysis, serum follicle stimulating hormone (FSH), and scrotal ultrasound were done before surgical exploration. Among the 198 men who were selected for surgical procedures, 159 candidates underwent microsurgical VE with sperm detected in the epididymal fluid. As for the other 39 cases, reconstruction was not feasible. The average age was 28.5 ± 3.9 years (range 22-38), with average follow-up being 16.5 ± 5.9 months (range 4-28). According to the 150 cases being followed after VE procedures, the total patency rate was 72% (108/150). During follow-up, 38.7% (58/150) natural pregnancies occurred, with overall live birth rate being 32.7% (49/150). Our data suggested that microsurgical VE is an effective therapy for postinfectious epididymal OA. Individualized counseling with prognosis based on etiology should be offered to patients to select optical therapy.

Renal AML with inferior vena cava thrombus treated by workbench surgery and autotransplantation.

Renal angiomyolipoma may sometimes require surgical intervention. In this paper, we present a case of renal angiomyolipoma which infiltrated the sinus and extended into the inferior vena cava. He was successfully treated with a combined approach of laparoscopic radical nephrectomy, extracorporeal workbench tumor resection, and autotransplantation. Three months postoperatively, no evidence of tumor recurrence or presence of thrombus in the inferior vena cava was noted. Our experience represents the successful application of a combined nephron-sparing approach in the management of angiomyolipoma with extension into a major blood vessel.

Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways.

BACKGROUND: Metformin is the first line of oral antidiabetic drug in the biguanide class for treatment of type 2 diabetes. Increasing evidence has suggested that it is a potential anti-tumor drug. However, the mechanisms underlying inhibiting tumor development remain elusive, especially in bladder tumors. METHODS: T24 and J82 cell lines were used as an in vitro model, and 24 female SD rats were used to build an N-methyl-N-nitrosourea (MNU)-induced orthotopic rat bladder cancer model. Transfection of lentivirus-based shRNA was used to construct the STAT3-KNOCKDOWN T24 cell line. After metformin treatment, the viability of bladde cancer cells was determined by CCK8. Cell cycle distribution and apoptosis were assessed by flow cytometry. The migration and invasion abilities of cells were evaluated by wound healing and transwell asssays. The inactivation of stat3 pahtway was examined by qRTPCR, western blot and Immunofluorescence. RESULTS: Metformin can effectively inhibit precancerous progression to invasive cancer in an MNU-induced rat orthotopic bladder tumor model, although it could not completely suppress normal cells transforming into tumor cells. While the MNU could induce 50 % rats (4/8) to develop invasive bladder cancers, the rats co-administrated with metformin failed to develop invasive tumors but retained at precancerous or non-invasive stages, exhibiting as dysplasia, papillary tumor and/or carcinoma in situ (CIS). Accordingly, phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is a well known oncogene, was significantly inhibited in the tumors of rats treated with metformin. In vitro experiments revealed that the metformin could efficiently inhibit STAT3 activation, which was associated with the cell cycle arrest, reduction of cell proliferation, migration and invasiveness, and increase in apoptotic cell death of bladder cancer cell lines. CONCLUSIONS: These findings provide for the first time the evidence that metformin can block precancerous lesions progressing to invasive tumors through inhibiting the activation of STAT3 pathway, and may be used for treatment of the non-invasive bladder cancers to prevent them from progression to invasive tumors.

NODAL secreted by male germ cells regulates the proliferation and function of human Sertoli cells from obstructive azoospermia and nonobstructive azoospermia patients.

This study was designed to explore the regulatory effects of male germ cell secreting factor NODAL on Sertoli cell fate decisions from obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) patients. Human Sertoli cells and male germ cells were isolated using two-step enzymatic digestion and SATPUT from testes of azoospermia patients. Expression of NODAL and its multiple receptors in human Sertoli cells and male germ cells were characterized by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Human recombinant NODAL and its receptor inhibitor SB431542 were employed to probe their effect on the proliferation of Sertoli cells using the CCK-8 assay. Quantitative PCR and Western blots were utilized to assess the expression of Sertoli cell functional genes and proteins. NODAL was found to be expressed in male germ cells but not in Sertoli cells, whereas its receptors ALK4, ALK7, and ACTR-IIB were detected in Sertoli cells and germ cells, suggesting that NODAL plays a regulatory role in Sertoli cells and germ cells via a paracrine and autocrine pathway, respectively. Human recombinant NODAL could promote the proliferation of human Sertoli cells. The expression of cell cycle regulators, including CYCLIN A, CYCLIN D1 and CYCLIN E, was not remarkably affected by NODAL signaling. NODAL enhanced the expression of essential growth factors, including GDNF, SCF, and BMP4, whereas SB431542 decreased their levels. There was not homogeneity of genes changes by NODAL treatment in Sertoli cells from OA and Sertoli cell-only syndrome (SCO) patients. Collectively, this study demonstrates that NODAL produced by human male germ cells regulates proliferation and numerous gene expression of Sertoli cells.