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.

Warm Acupuncture Reduces Pain and Inflammation in Rats with Lumbar Disc Herniation Induced by Autologous Nucleus Pulposus Transplantation via Regulating p38MAPK/NF-κB Pathway.

Background: : Warm acupuncture (WA) has analgesic and anti-inflammatory effects. However, the underlying mechanism of these effects remain unclear. Objectives: : To explore the analgesic and anti-inflammatory effects of WA and the potential underlying mechanism in male Sprague-Dawley rats with non-compressive lumbar disk herniation (LDH) caused by autologous nucleus pulposus (NP) transplantation. Methods: : We used low-frequency (2 Hz) electrical stimulation and WA (40℃) to treat GB30 and BL54 acupoints in rats for 30 mins per day. We monitored the paw withdrawal threshold of rats during the experiment and measured serum cytokine levels using commercial kits. Dorsal root ganglion (DRG) tissue pathology was analyzed via H&E staining. We used qRT-PCR to measure the mRNA expression levels of IL-1ß, IL-6, and TNF-α genes in DRG. Western blot was used to analyze the expression levels of IL-1ß, IL-6, TNFα, P-p38MAPK, p38MAPK, P-IκBα, IκB α, and NF-κB p65 proteins. Results: : WA treatment significantly increased the pain threshold of rats, reduced serum IL-6, PEG2, NO, SP, NP-Y, and MMP-3 levels, and effected histopathological improvements in the DRG in rats. Moreover, WA treatment significantly downregulated the expression levels of inflammation-associated genes (Il-1ß, Il-6, and Tnf-α) and proteins (IL-1ß, IL-6, TNF-α, P-p38MAPK, P-IκBα, and NF-κB p65) in the DRG of non-compressive LDH rats. Conclusion: : WA can alleviate pain and inhibit inflammatory response in rats with non-compressive LDH caused by autologous NP transplantation, and these effects are likely associated with the inhibition of the p38MAPK/NF-κB pathway.

Qishen granules regulate intestinal microecology to improve cardiac function in rats with heart failure.

Introduction: Qishen Granule (QSG), a clinically approved traditional Chinese medicine, has been researched for treating heart failure (HF) for many years. However, the effect of QSG on intestinal microecology remains unconfirmed. Therefore, this study aimed to elucidate the possible mechanism of QSG regulating HF in rats based on intestinal microecological changes. Methods: A rat model with HF induced by myocardial infarction was prepared by left coronary artery ligation. Cardiac functions were assessed by echocardiography, pathological changes in the heart and ileum by hematoxylin-eosin (HE) and Masson staining, mitochondrial ultrastructure by transmission electron microscope, and gut microbiota by 16S rRNA sequencing. Results: QSG administration improved cardiac function, tightened cardiomyocytes alignment, decreased fibrous tissue and collagen deposition, and reduced inflammatory cell infiltration. Electron microscopic observation of mitochondria revealed that QSG could arrange mitochondria neatly, reduce swelling, and improve the structural integrity of the crest. Firmicutes were the dominant component in the model group, and QSG could significantly increase the abundance of Bacteroidetes and Prevotellaceae_NK3B31_group. Furthermore, QSG significantly reduced plasma lipopolysaccharide (LPS), improved intestinal structure, and recovered barrier protection function in rats with HF. Conclusion: These results demonstrated that QSG was able to improve cardiac function by regulating intestinal microecology in rats with HF, suggesting promising therapeutic targets for HF.

Effect of the pectin contents and nanostructure on the stem straightness of two Paeonia lactiflora cultivars.

Herbaceous peony (Paeonia lactiflora Pall.) is an ancient ornamental crop and, in recent decades, an emerging popular cut flower. Straight stems are a vital criterion for cut herbaceous peony selection, while many cultivars bend as the plant develops. Pectin helps maintain the mechanical strength of the cell wall. However, little is known about its role in the stem bending of herbaceous peony. Two herbaceous peony cultivars with contrasting stem morphologies ('Dong Fang Shao Nv', upright; 'Lan Tian Piao Xiang', bending gradually) at five developmental stages were used as materials to investigate the effects of pectin content and nanostructure on straightness using the carbazole colorimetric method and atomic force microscopy observations. The contents of water-soluble pectin (WSP), CDTA-soluble pectin (CSP), and sodium carbonate-soluble pectin (SSP) differed significantly between the two cultivars, and the contents and angle of the flower and branch showed correlations. For the pectin nanostructure, WSP showed agglomerates and long chains, with a higher proportion of broad agglomerates at the later stages of the bending cultivar than the upright cultivar. CSP showed branched chains, and the proportion of broad chains was higher in the upright cultivar at later stages, while CSP shape changed from agglomerates to chains in the bending cultivar. SSP mainly consisted of short linear main chains, and side chains in the upright stem were stacked, and the bent cultivar had more broad and short chains. It can be concluded that the contents, nanometric shape, and size of the three kinds of pectin are highly likely to affect herbaceous peony stem straightness. This study provides a theoretical basis for the role of pectin in the production and breeding of herbaceous peony cut flowers.

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.

[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.

Needling on trigger point promotes muscle regeneration after bupivacaine injection induced injury.

Dry needling treatment has a promising relieving effect on Myofascial Pain Syndrome (MPS). In China, acupuncture practitioners use acupuncture needle instead to insert the "A-Shi" acupoint to treat MPS which is defined as the same as the trigger point of dry needling. This method has been applied for thousands of years in China. In this study, bupivacaine injection induced gastrocnemius muscle injury in mice. We applied the clinical improved needling method on animal model by making the angle between the skin and needle less than 30 degree. Animals got needling treatment 24 h later at the point where the bupivacaine was injected. Results of muscle H.E. staining showed that, compared to bupivacaine injection group without needling, acupuncture treatment group showed more intact muscle fibers, less inflammatory cell infiltration and fractured muscle fibers. By RNA sequencing analysis, our work firstly demonstrated that the physical stimulation of needling changed the gene expression of muscle tissue to accelerate the muscular regeneration process. Therefore, our study proved that simple needling at "A-Shi" acupoint promoted muscle regeneration and revealed underlying mechanisms of the beneficial effects of acupuncture and dry needle treatments.

Expression of PBRM1 as a prognostic predictor in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitor.

OBJECTIVE: PBRM1, located on 3p21, functions as a tumor suppressor and somatic mutation of PBRM1 is frequent in clear cell renal cell carcinoma (ccRCC). This study aims to determine the influence of PBRM1 expression on the prognosis of patients with mRCC receiving tyrosine kinase inhibitor (TKI) treatment. METHODS: We identified 116 mRCC patients who were administered sunitinib or sorafenib as first-line therapy, between January 2006 and December 2016 at our institution. PBRM1 expression was assessed by immunohistochemistry. The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS), log-rank test was used to compare the survival outcomes between patients with low and high PBRM1 expression levels, and the Cox proportional hazard regression model was used to estimate the prognostic value. Prognostic accuracy was determined using Harrell concordance index, and nomograms were built to evaluate the prognosis of mRCC. RESULTS: Patients with low PBRM1 expression had significantly shorter median PFS (9 vs 26 months, P < 0.001) and OS (21 vs 44 months, P < 0.001) than those with high expression. Multivariate analysis showed that PBRM1 expression was an independent predictor of PFS (HR 1.975, P = 0.013) and OS (HR 2.282, P = 0.007). The model built by the addition of PBRM1 improved the C-index of PFS and OS to 0.72 and 0.82, respectively. CONCLUSIONS: The expression of PBRM1 could be a significant prognostic factor for mRCC patients treated with targeted therapy, and it increases the prognostic accuracy of the established prognostic model.

[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.

Sunitinib or Sorafenib as Neoadjuvant Therapy May not Improve the Survival Outcomes of Renal Cell Carcinoma with Tumor Thrombus.

OBJECTIVES: The purpose of this work was to investigate the effect of sorafenib or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell carcinoma (RCC) with tumor thrombus. METHODS: A total of 92 RCC patients with tumor thrombus were included in this 2-center retrospective research from January 2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant therapy in 9 patients and 14 patients, respectively, and 69 patients constituted non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used to compare the survival outcomes of patients with or without neoadjuvant therapy. RESULTS: The overall median RFS and OS time for all 92 patients were 28 months (95% CI 17-39 months) and 42 months (95% CI 30-54 months). Patients with neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p = 0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant therapy. CONCLUSIONS: Neoadjuvant therapy of sorafenib or sunitinib might not improve survival outcomes for high risk RCC patients with tumor thrombus. Thus, neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously.

Curcumin inhibits cell proliferation and motility via suppression of TROP2 in bladder cancer cells.

Bladder cancer (BC) has become a serious health prob-lem and represents the second most commonly diagnosed urological tumor. Curcumin is a principal active natural component of turmeric and has long been used in Asia as a traditional herbal medicine. Curcumin suppresses cell growth in various types of cancer, including BC, by regulating numerous molecular signaling pathways. The human trophoblast cell surface antigen 2 (Trop2) belongs to the tumor-associated calcium signal transducer gene family. Trop2 has been described as a cancer driver and is deregulated in various types of cancer. However, whether Trop2 is involved in curcumin-induced BC cell inhibition remains to be elucidated. The present study hypothesized that Trop2 may be a promising target of curcumin in BC cells. It was found that Trop2 was closely involved in curcumin-induced cell proliferation suppression, mobility inhibition, apoptosis, and cell cycle arrest in BC cells. Curcumin decreased the expression of Trop2 and its downstream target cyclin E1, and increased the level of p27. The overexpression of Trop2 enhanced the oncogenic activity of BC cells, whereas downregulation of the expression of Trop2 suppressed cell proliferation and mobility, increased apoptosis, and sensitized BC cells to curcumin treatment. Therefore, Trop2 may be a promising target of curcumin in BC cells and the inhibition of Trop2 may be an important method for the therapeutic management of patients with BC.

Significance of preoperative prognostic nutrition index as prognostic predictors in patients with metastatic renal cell carcinoma with tyrosine kinase inhibitors as first-line target therapy.

OBJECTIVE: Prognostic nutritional index (PNI) is a recognized indicator of both immune and nutritional status. It was firstly used as a preoperative prognostic indicator, and its role in the prognosis of patients with metastatic renal cell carcinoma (mRCC) has not yet been investigated in large-scale study. The purpose of this work was to investigate the prognostic role of pretreatment PNI in patients with mRCC with sorafenib or sunitinib as first-line targeted therapy. METHOD: In this retrospective single-center research, the Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS) of 178 mRCC patients who received first-line therapy of sorafenib or sunitinib. Log-rank test was used to compare the survival outcomes of patients with low pretreatment PNI (PNI < 51.62) and high pretreatment PNI (PNI ≥ 51.62), and Cox proportional hazard regression model was used to compare PFS and OS between these two groups. Prognostic accuracy was determined using Harrell concordance index. RESULTS: The overall median PFS and OS time for all 178 patients were 11 months (95% CI 9-12 months) and 24 months (95% CI 19-33 months), respectively. Patients with low pretreatment PNI both had significantly shorter median PFS (7 vs 19 months, P < 0.001) and OS (14 vs 50 months, P < 0.001) than those with high PNI. Multivariate analysis showed that pretreatment PNI was an independent predictor of OS (HR 1.658, 95% CI 1.040-2.614, P = 0.033) and an independent predictor of PFS as well (HR 1.842, 95% CI 1.226-2.766, P = 0.003). The model built by the addition of pretreatment PNI improved predictive accuracy of PFS and OS compared with the International Metastatic Renal Cell Carcinoma Database Consortium Model (Heng model) (c-index: 0.68 and 0.70). Comparing to NLR (neutrophil-to-lymphocyte ratio) (0.69 and 0.72), PNI might be a preciser factor to predict PFS and OS (0.71 and 0.73). CONCLUSIONS: Low pretreatment PNI could be a significant risk factor for mRCC patients who received tyrosine kinase inhibitors as first-line target therapy and increase the accuracy of established prognostic model.

Comparison of efficacy, safety, and quality of life between sorafenib and sunitinib as first-line therapy for Chinese patients with metastatic renal cell carcinoma.

BACKGROUND: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma (mRCC) in China. This study aimed to compare the efficacy, safety, and quality of life (QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy. METHODS: Clinical data of patients with mRCC who received sorafenib (400 mg twice daily; 4 weeks) or sunitinib (50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival (OS), progression-free survival (PFS), adverse events (AEs), and QoL (SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL. RESULTS: Medical records of 184 patients (110 in the sorafenib group and 74 in the sunitinib group) were reviewed. PFS and OS were comparable between the sorafenib and sunitinib groups (both P > 0.05). The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group (36.5% vs. 10.9%, P < 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group (62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs (P = 0.017 and 0.005). CONCLUSIONS: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.

Association of post-treatment hypoalbuminemia and survival in Chinese patients with metastatic renal cell carcinoma.

BACKGROUND: Hypoalbuminemia adversely affects the clinical outcomes of various cancers. The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma (mRCC) who received sorafenib or sunitinib as first-line treatment. METHODS: In this single-center, retrospective study, we assessed the progression-free survival (PFS) and overall survival (OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment. PFS and OS were compared between patients with post-treatment hypoalbuminemia (post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level (albumin level ≥36.4 g/L). The Memorial Sloan Kettering Cancer Center (MSKCC) risk model stratified mRCC patients into three risk categories. Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models. Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis. RESULTS: The median PFS and OS of the 184 patients were 11 months (95% confidence interval [CI] 9-12 months) and 23 months (95% CI 19-33 months), respectively. Patients with post-treatment hypoalbuminemia had significantly shorter median PFS (6 months [95% CI 5-7 months]) and OS (11 months [95% CI 9-15 months]) than patients who had normal post-treatment albumin levels (PFS: 12 months [95% CI 11-16 months], P < 0.001; OS: 31 months [95% CI 24-42 months], P < 0.001), respectively. Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS (hazard ratio [HR], 2.113; 95% CI 1.390-3.212; P < 0.001) and OS (HR, 2.388; 95% CI 1.591-3.585; P < 0.001). Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS. The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS (c-index: 0.68 and 0.73, respectively) compared with the basic MSKCC risk model (c-index: 0.67 and 0.70, respectively). The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis (both P < 0.001). CONCLUSIONS: Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors. Additionally, integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.

Pretreatment Serum Prealbumin as an Independent Prognostic Indicator in Patients With Metastatic Renal Cell Carcinoma Using Tyrosine Kinase Inhibitors as First-Line Target Therapy.

BACKGROUND: Although serum prealbumin is a sensitive marker to assess malnutrition, its prognostic impact in patients with metastatic renal cell carcinoma (mRCC) remains elusive. METHODS: Patients' data were retrospectively retrieved from the medical records of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from March 2006 to July 2015 to access overall survival (OS) and progression-free survival (PFS). The survival outcomes of patients with low pretreatment prealbumin (< 200 mg/L) and high pretreatment prealbumin (≥ 200 mg/L) were compared using a log-rank test and Cox proportional hazard regression model. Prognostic accuracy was determined using the Harrell concordance index (c-index). RESULTS: The median PFS and OS for 143 patients were 11 months (95% confidence interval [CI], 9-14 months) and 27 months (95% CI, 22-39 months), respectively. The low pretreatment prealbumin group had significantly shorter median PFS (6 vs. 14 months, P < .001) and OS (10 vs. 34 months, P < .001) than the normal pretreatment prealbumin group. Multivariate analysis showed that pretreatment prealbumin was an independent predictor of OS (hazard ratio [HR] 1.963; 95% CI, 1.140-3.381; P = .015) and also an independent predictor of PFS (HR 2.021; 95% CI, 1.227-3.329; P = .006). Further, addition of pretreatment prealbumin to the Heng model enhanced the predictive accuracy of PFS and OS (c-index: 0.70 and 0.74) compared with the Heng model alone (c-index: 0.69 and 0.72). CONCLUSION: Low pretreatment serum prealbumin is an independent prognosticator of risk and survival outcomes in patients with mRCC receiving tyrosine kinase inhibitors as first-line treatment and also increases the accuracy of established prognostic models.

[The effect of acupuncture stimulation of Ashi-point on hepatocyte growth factor expression in the soft tissue in acute contusion rats].

OBJECTIVE: To observe the effect of acupuncture stimulation of Ashi-point on hepatocyte growth factor (HGF) protein expression in gastrocnemius muscle (GM) in rats with traumatic injury of GM, so as to reveal its mechanism underlying improvement of traumatic injury of skeletal muscle. METHODS: A total of 80 SD rats were randomly divided into normal control (n = 8), model, acupuncture control, and acupuncture treatment groups, and the latter 3 groups were further allocated to 0 h, 24 h and 48 h subgroups (n = 8 in each subgroup). The acute soft tissue contusion model was established by using 500 g-counterweight free falling hitting at the GM of the right leg (height 30 cm). The Ashi-point was punctured with a piece of filiform needle by penetrating the site beside the injured GM, and stimulated for about 5 seconds. For acupuncture control group, acupuncture was performed in the same Ashi-point in normal rats. Pathological changes of the focal GM were observed by H. E. staining and HGF protein expression of GM was detected by Western blot. RESULTS: H.E. staining showed that different degrees of injury of GM tissue including broken muscle fibers with cellular swelling, inflammatory cell infiltration, muscle fibrinolysis, atrophy, degeneration and necrosis, etc., were found at each time-point after modeling, while in the acupuncture treatment group, the severity of muscle injury was relatively milder particularly at the time-points of 24 h and 48 h. Compared with the normal control group, HGF protein expression levels of GM at the 3 time-points in the model group, and at 48 h in the acupuncture control group were markedly increased (P<0.05, P<0.01); while in comparison with the model group, HGF protein expression levels were remarkably down-regulated at 24 h and 48 h after acupuncture treatment (P<0.01, P<0.05). CONCLUSION: Acupuncture stimulation of Ashi-point can significantly down-regulate HGF protein expression in the GM in soft tissue contusion rats, which may contribute to its effects in relieving contusion injury of skeletal muscle.

Catalpol Inhibited the Proliferation of T24 Human Bladder Cancer Cells by Inducing Apoptosis Through the Blockade of Akt-Mediated Anti-apoptotic Signaling.

Catalpol is an iridoid glucoside extracted from the traditional Chinese medicinal plant called Rehmannia glutinosa, and it is reported to possess a variety of pharmacological activities. The goal of this research was to explore the effect of catalpol on the human bladder cancer cells T24. The cells were treated for different durations with various concentrations of catalpol. Then the viability, mobility, and invasiveness of the cells were determined by MTT assay and flow cytometry, respectively. Catalpol was found to significantly suppress the proliferation, migration, and invasiveness of T24 bladder cancer cells in a dose- and time-dependent manner. The results also revealed that catalpol promoted apoptosis and caused the cell-cycle arrest at G2/M phase. Furthermore, the catalpol-mediated apoptosis was found to involve the modulation of PI3K/Akt pathway and inhibit the expression of anti-apoptotic B cell lymphoma-2 (Bcl-2) family proteins. Also, the expressions of Bcl-2 proapoptotic effectors, Bcl-2-associated X protein, and Bcl-2 associated death promoter were up-regulated in the cells treated with catalpol. The enzymes involved in the ultimate process of apoptosis, active caspase-3 and poly ADP ribose polymerase were elevated, and the latter was observed to be cleaved, indicating that catalpol-accelerated cell apoptosis involved a caspase-dependent pathway. These results suggest that catalpol might serve to be a promising therapeutic agent for the treatment of human bladder cancer.

[Effects of acupotomy, electroacupuncture or round-sharp acupuncture needle interventions on expression of Bcl-2, Bax, Caspase-3 proteins of rectus femoris in rabbits with knee ostarthritis].

OBJECTIVE: To observe the effect of acupotomy, electroacupuncture (EA) or round-sharp acupuncture needle intervention on the expression of Bcl-2,Bax and Caspase-3 proteins in the rectus femoris in rabbits with knee ostarthritis (KOA), so as to explore their mechanisms underlying improvement of braking-induced joint damage from the cellular apoptosis. METHODS: Forty-five New Zealand rabbits were equally and randomized into control group, model group, acupotomy (AP) group, EA group and round-sharp acupuncture needle (RSAN) group (n = 9 in each group). The knee-joint injury model was established by fixing the left knee joint in extention position with plaster bandage. EA (2 Hz/100 Hz, 3 mA, 20 min each time) was applied to the left "Yanglingquan" (GB 34)- "Yinlingquan" (SP 9) and left "Neixiyan" (EX-LE 4)- "Waixiyan"(ST 35) for rabbits in the EA group. The EA treatment was given once daily, 3 times a week, 3 weeks in total. For rabbits of the AP group, a needle-knife was held to insert into the front edge of the midpoint, the starting point and the stopping point of the left medial collateral ligamen, lateral collateral ligament and the patellar ligament of the knee to make a loosening manipulation for 5 times in a session of treatment, once a week, 3 times altogether. For rabbits of the RSAN group, a round-sharp needle was performed in the same way to the needle-knife including the stimulation point, the manipulation method and treatment sessions. At the end of the experiment, the left rectus femoris was taken out for detecting the expression of Bcl-2, Bax and Caspase-3 proteins with Western blot. RESULTS: In comparison with the control group, the passive range of motion (PROM) level was significantly decreased 4, 8 and 12 weeks after modeling (P < 0.01), and the expression levels of Bax and Caspase-3 proteins in the rectus femoris were considerably upregulated in the model group (P < 0.05), while the ratio of Bcl-2/Bax was notably down-regulated (P < 0.05) in the model group. Compared with the model group, the PROM level at week 12 after modeling in the AP, EA and RSAN groups were significantly increased (P < 0.01); while Bax and Caspase-3 expression levels in both AP and RSAN groups were considerably downregulated (P < 0.05). No significant differences were found among the five groups in Bcl-2 expression levels (P > 0.05), and between the EA and model groups in Bax and Caspase-3 expression levels and the ratio of Bcl-2/Bax (P > 0.05). CONCLUSION: AP, RSAN and EA interventions are effective in improving the knee-joint motion range in KOA rabbits, and this effect of both AP and RSAN is closely associated with their actions in lowering the expression of Bax and Caspase-3 proteins of the rectus femoris and in raising ratio of Bcl-2/Bax protein (reducing muscular cellular apoptosis). The mechanism of EA intervention in improving PROM may be different.

[Treatment of varicocele infertility men patients of different Chinese medical syndrome types by integrative medicine treatment selection: a primary research].

OBJECTIVE: To explore the optimal treatment selection for treating varicocele (VC) male infertility patients accompanied with oligozoospermia or azoospermia of different Chinese medical syndrome types by comparing the efficacies of integrative medicine. METHODS: One hundred and twenty male infertility patients with VC accompanied with oligozoospermia or azoospermia were assigned to Chinese medical treatment group (A) and the surgical group (B), each consisting of three Chinese medical syndrome types, i.e., damp-heat stagnation syndrome (DHSS), Shen-deficiency blood stasis syndrome (SDBSS), and blood stasis stagnation syndrome (BSSS), 20 in each group. Corresponding Chinese medical treatment was administered to those in Group A, C, and E, while microscopic ligation of internal vena spermatic was administered to those in Group B, D, and F. The routine analysis of semen, biochemical analysis of seminal plasma, and serum sex hormones (prolactin, testosterone, follicle stimulating hormone, luteinizing hormone, and estradiol) were performed before treatment and by the end of the 24th week after treatment. RESULTS: Totally 18 patients' spouses were pregnant. Of them, 1 in Group A of DHSS (abbreviated as Group A), 3 in Group B of DHSS (abbreviated as Group B), 4 in Group A of SDB-SS (abbreviated as Group C), 5 in Group A of SDBSS (abbreviated as Group D), 1 in Group A of BSSS (abbreviated as Group E), and 4 in Group B of BSSS (abbreviated as Group F). After 24-week treatment, the sperm concentration, class a sperm percentage, class a + b sperm percentage, the motility rate, the seminal plasma of fructose density, and the seminal plasma neutral alpha-glucosidase were more significantly improved in Group B, C, D and F, when compared with the same group before treatment (P <0. 01, P <0. 05). There was no statistical difference in the aforesaid indices between before and after treatment in Group A and Group E (P >0.05). As for the improvement percentage of seminal routine indices, the difference of the seminal plasma of fructose density, and the difference of seminal plasma neutral alpha-glucosidase between before and after treatment in the same Chinese medical syndrome types, better effects were obtained in Group B than in Group A (P <0.01), and better effects were obtained in Group F than in Group E (P <0.01). There was no statistical difference between Group C and D (P >0.05). There was no statistical difference in the 5 items of sex hormones in each group between before and after treatment (P >0.05). CONCLUSIONS: Surgical treatment could effectively improve the semen quality for male infertility VC patients accompanied with oligozoospermia or azoospermia. Of them, Chinese medical treatment could be recommended to those of SDBSS who would not receive surgical treatment.