Short-term and long-term effectiveness of acupuncture and Tuina on knee osteoarthritis: study protocol for a randomized controlled trial.

Background: The effectiveness of acupuncture and tuina in treating knee osteoarthritis (KOA) is still controversial, which limits their clinical application in practice. This study aims to evaluate the short-term and long-term effectiveness of acupuncture and tuina on KOA. Methods/design: This parallel-group, multicenter randomized clinical trial (RCT) will be conducted at the outpatient clinic of five traditional Chinese medicine hospitals in China. Three hundred and thirty participants with KOA will be randomly assigned to acupuncture, tuina, or home-based exercise group with a ratio of 1:1:1. The primary outcome is the proportion of participants achieving a minimal clinically important improvement defined as a ≥ 12% reduction on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain dimension on short term (week 8) and long term (week 26) compared with baseline. Secondary outcomes are knee joint conditions (pain, function, and stiffness), self-efficacy of arthritis, quality of life, and psychological conditions, which will be evaluated by the WOMAC score and the Patient Global Assessment (PGA), and in addition, the respondents index of OMERACT-OARSI, Short Form 12 Health Survey (SF-12), arthritis self-efficacy scale, and European five-dimensional health scale (EQ-5D). Adverse events will be collected by self-reported questionnaires predefined. Clinical trial registration: https://www.chictr.org.cn.

[The role of cholesterol metabolism reprogramming in pancreatic cancer and the application of cholesterol-targeted metabolism drugs].

Pancreatic cancer has an insidious onset and lacks effective treatment methods, which is one of the tumors with the worst prognosis, so it is urgent to explore new treatment directions. Metabolic reprogramming is one of the important hallmarks of tumors. Pancreatic cancer cells in the harsh tumor microenvironment have comprehensively increased cholesterol metabolism in order to maintain strong metabolic needs, and cancer associated fibroblasts also provide cancer cells with a large amount of lipids. Cholesterol metabolism reprogramming involves the changes in the synthesis, uptake, esterification and metabolites of cholesterol, which are closely related to the proliferation, invasion, metastasis, drug resistance, and immunosuppression of pancreatic cancer. Inhibition of cholesterol metabolism has obvious anti-tumor effect. In this paper, the important effects and complexity of cholesterol metabolism in pancreatic cancer were comprehensively reviewed from perspectives of risk factors for pancreatic cancer, energy interaction between tumor-related cells, key targets of cholesterol metabolism and its targeted drugs. Cholesterol metabolism has a strict regulation and feedback mechanism, and the effect of single-target drugs in clinical application is not clear. Therefore, multi-target therapy of cholesterol metabolism is a new direction for pancreatic cancer treatment.

Study of biological activity and targeted distribution of catesbeianalectin in mouse tissue.

Lectin has attracted attention because of its ability to serve as a carrier for targeted drug delivery. Large lectins isolated from marine invertebrates and crustaceans have strong immunogenicity and adverse effects, which limit their usefulness. This study reports the identification of catesbeianalectin via screening a bullfrog skin cDNA library. The catesbeianalectin polypeptide has a molecular weight of 1.47 kD, making it the smallest known lectin in terms of molecular weight. Circular dichroism analysis showed a PPII helix secondary structure. Catesbeianalectin strongly induces agglutination of rabbit erythrocytes and a variety of pathogens include Staphylococcus aureus, Streptococcus suis type 2, Actinobacillus pleuropneumoniae, and piglet paratyphoid Salmonella. The mean serum titer in catesbeianalectin-immunized Balb/c mice was 1:25, which was significantly lower than that of positive controls immunized with wheat germ agglutinin. Surface plasmon resonance indicated an S-type lectin. 125I-labeled catesbeianalectin did not pass the blood-brain barrier. This study provides a basis for further research on the potential of catesbeianalectin as a carrier in targeted drug delivery.

PSMD7 downregulation induces apoptosis and suppresses tumorigenesis of esophageal squamous cell carcinoma via the mTOR/p70S6K pathway.

PSMD7, a 19S proteasome subunit, is overexpressed in most carcinoma cells. It forms a dimer with PSMD14 that functions in the removal of attached ubiquitin chain. However, there is little knowledge about the cellular mechanism of PSMD7 and its exact biological function, especially in cancer cells. In this study, we explored the role of PSMD7 in proliferation, cell cycle, apoptosis, and proteasomal proteolysis in the esophageal squamous cell carcinoma (ESCC) cell line EC9706. Our results showed that PSMD7 was highly expressed in ESCC cells. Downregulation of PSMD7 by lentivirus-mediated shRNA led to decreased proliferation, increased cell apoptosis, and reduced proteasomal function. Notably, lower expression level of mTOR and p70S6K and suppressed activity of mTOR/p70S6K pathway were detected after PSMD7 downregulation. By contrast, increased expression of p-mTORSer2448 and p-p70S6KThr421/Ser424 was discovered upon PSMD7 overexpression in Het-1A cells. Furthermore, PSMD7 downregulation contributed to decelerated tumor growth, inhibition of proteasomal function, induced cell apoptosis and attenuated activity of mTOR/p70S6K pathway in vivo. These findings suggest that PSMD7 and the mTOR/p70S6K pathway may be a promising candidate for developing therapies for ESCC.

Effect of Acupotomy on FAK-PI3K Signaling Pathways in KOA Rabbit Articular Cartilages.

OBJECTIVE: By observing the needle-knife of KOA rabbit morphology, knee joint cartilage p-FAK, p-PI3K, Aggrecan gene, and protein expression, to study the effect of needle-knife to promote cartilage cell synthesis metabolism mechanism. METHOD: 49 male New Zealand rabbits, randomly divided into normal group (Z), model group (M), model-inhibitors (MP), needle-knife group (D), needle-knife inhibitors group (DP), electroacupuncture group (E), and electroacupuncture inhibitors (EP). RT-PCR and Western Blot were used to test each animal cartilage p-FAK, p-PI3K, and Aggrecan gene and protein expression level. RESULTS: Compared with N group, p-FAK and p-PI3K protein and mRNA expression of M group, D group, and E group increased (P < 0.05), while the protein and mRNA expression of Aggrecan reduced (P < 0.05). Compared with M group, p-FAK, p-PI3K, Aggrecan protein, and mRNA of E and D group increased (P < 0.05). Compared with E group, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression of D group increased (P < 0.05); after adding inhibitors, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression reduced (P < 0.05). CONCLUSION: Needle-knife therapy can promote the repairment of cartilage cells by activating FAK-PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism.

Correction: Acupuncture with reinforcing and reducing twirling manipulation inhibits hippocampal neuronal apoptosis in spontaneously hypertensive rats.

[This corrects the article on p. 770 in vol. 12, PMID: 28616034.].

Acupuncture with reinforcing and reducing twirling manipulation inhibits hippocampal neuronal apoptosis in spontaneously hypertensive rats.

To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats (SHRs), this study used the reinforcing twirling method (1.5-2-mm depth; rotating needle clockwise for 360° and then counter clockwise for 360°, with the thumb moving heavily forward and gently backward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), the reducing twirling method (1.5-2-mm depth; rotating needle counter clockwise for 360° and then clockwise for 360°, with the thumb moving heavily backward and gently forward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), and the needle retaining method (1.5-2-mm depth and retaining the needle for 10 minutes). Bilateral Taichong (LR3) was treated by acupuncture using different manipulations and manual stimulation. Reinforcing twirling, reducing twirling, and needle retaining resulted in a decreased number of apoptotic cells, reduced Bax mRNA and protein expression, and an increased Bcl-2/Bax ratio in the hippocampus compared with the SHR group. Among these groups, the Bcl-2/Bax protein ratio was highest in the reducing twirling group, and the Bcl-2/Bax mRNA ratio was highest in the needle retaining group. These results suggest that reinforcing twirling, reducing twirling, and needle retaining methods all improve blood pressure and prevent target organ damage by increasing the hippocampal Bcl-2/Bax ratio and inhibiting cell apoptosis in the hippocampus in SHR.

[Surgical treatment of primary hyperparathyroidism].

OBJECTIVE: To investigate the causes of misdiagnosis and the surgical treatment of primary hyperparathyroidism (PHPT). METHODS: The clinical data of 26 patients with PHPT from July 2008 to January 2013 in The Affiliated Hospital of Chengde Medical College and The Fourth Hospital of Hebei Medical University were retrospectively analyzed, including preoperative diagnosis and operative method. The level of serum calciumion and serum parathyroid hormone (PTH), Ultrasonography, CT, (99)mTc-methoxy isobutylis onitrile ((99)mTc-MIBI) were used in the diagnosis before operation. All patients accepted surgical treatment after the level of serum calciumion decreased to normal. RESULTS: The level of PTH was examined 10 min after resection, which declined more than 50%. After pathological examination, 23 cases were diagnosed as parathyroid adenoma, 2 cases were parathyroid hyperplasia, and 1 case was parathyroid carcinoma. The level of serum calciumion and serum parathyroid hormone were returned to the normal level after operation. All patients recovered with no postoperative complication.Followed up lasted from 6 months to 5 years, no case recurred.Sixteen cases with symptoms experienced significant improvement in signs, including 10 cases with clinical symptoms completely disappeared. CONCLUSIONS: The test of serum calciumion and serum PTH, Ultrasonography, CT, (99)mTc-MIBI are helpful to reduce the misdiagnose rate of primary hyperparathyroidism before operation. The examination of serum parathyroid hormone in operation is helpful to reduce the operation range and time.

[Diagnosis and treatment of pharyngoesophageal diverticulum].

OBJECTIVE: To investigate the diagnosis, differential diagnosis and the treatment of Zenker diverticulum (pharyngo esophagus diverticulum) in thyroid operation. METHODS: Seven cases suffering from thyroid masses diagnosed Zenker diverticulum in thyroid operation between July 2001 and December 2011 were reviewed. RESULTS: Zenker diverticula in the patients were resected. Only one case was complicated with the formation of false capsular bag, infection and fistula postoperatively, but cured with draining eventually. CONCLUSIONS: Zenker diverticulum may exist in some patients with thyroid mass. Resection of diverticulum may be performed in thyroid operation, with a good prognosis.

[Phonation reconstruction and function assessment after total and near-total laryngectomy].

BACKGROUND & OBJECTIVE: Total laryngectomy is a common surgery pattern for treating laryngeal and hypopharyngeal cancer, but patients will lost phonation function after operation. This study was to retrospectively analyze usage of modified Amatsu, and modified Pearson operation in treating laryngeal and hypopharyngeal cancers, and to analyze phonation function by subjective and objective assessment. METHODS: Clinical data of 69 patients with laryngeal or hypopharyngeal cancer treated by total or near-total laryngectomy (modified Amatsu or modified Pearson operation) in our department from 1996 to 2003 were retrospectively analyzed. Phonation function of 69 patients was evaluated by acoustic analysis and Jiyan classification method, and compared with phonation quality of patients received vertical hemilaryngectomy (VHL) and healthy people. RESULTS: No patient appeared obvious aspiration. Four cases with post-operative radiotherapy all regained phonation function. The 3-year survival rate was 88% (22/25); 5-year survival rate was 80% (4/5). Results of acoustic assessment, and Jiyan classification method indicated that phonation function of patients received modified Amatsu or modified Pearson operation could meet daily requirements. CONCLUSIONS: Modified Amatsu and modified Pearson operations can be learnt and applied easily for phonation reconstruction after laryngectomy. They may be optional surgery patterns, especially modified Pearson operation.

[Surgical treatment of advanced thyroid carcinoma with aero-digestive invasion].

OBJECTIVE: To study the surgical management of the advanced thyroid carcinoma with aero-digestive invasion. METHODS: To analyze 18 cases of advanced thyroid carcinoma which had aerodigestive invasion retrospectively, the patients were treated from 1988 to 1998. RESULTS: The rate of aerodigestive invasion occur was 3.5% (18/516), The inner cavity invaded rate was 2.7% (14/516). The most invaded organ was trachea; The others were esophagus and larynx, pharynx; Two and/or more organs invaded rates were 44. 4% (8/18). The cases that survived 1, 3, 5 and 10 year were 17, 14, 9 and 6. The 5 years survival rates of the differentiated thyroid cancer (61.5%) were more higher than the undifferentiated thyroid cancer (20.0%), but there were no statistical difference between them (P > 0.05) and the same in clinical stage (P > 0.05). CONCLUSIONS: Intraluminal extension is a more serious problem in which usually extensive resection of the aerodigestive tract is required. Effective surgical treatment combined with postoperative auxiliary management for this kind of patients may achieve a good long term results.

[Combined treatment for advanced laryngeal carcinoma].

OBJECTIVE: To assess the efficacy of the combined therapy for advanced laryngeal carcinoma. METHODS: 204 cases of advanced laryngeal carcinoma were treated in this department from 1984 to 1997. Patients were treated by surgery alone or combined therapy including of surgery, radiotherapy and chemotherapy. RESULTS: The overall 3 and 5 year survival were 70.1% (143/204) and 61.8% (126/204) respectively. 5-year survival rate of the combined therapy group was 68.2% (90/132), whereas, 5-year survival was only 50.0% (36/72) for surgery alone group (P < 0.05). There was no statistical differences between surgery alone group and the combined therapy group in the local recurrences (P > 0.05) but distant metastases (P < 0.05). There were also no statistical differences between the preoperative radiotherapy group and the non-preoperative radiotherapy group in the terms of infection and fistula (P > 0.05). CONCLUSION: The results suggest that the combined therapy was more effective than surgery alone for the treatment of the advanced laryngeal carcinoma. Preoperative radiotherapy did not increase the incidences of infection and fistula.

[Diagnosis and surgical management of Hashimoto's disease coexistent with thyroid carcinoma].

OBJECTIVE: To study clinical assessment and management of the Hashimoto's disease coexistent with thyroid carcinoma. METHODS: A retrospective analysis in 182 cases of Hashimoto's disease treated from 1982 to 1998 were undertaken. The preoperation assessment, surgical management and the complication after operation had been studied. RESULTS: Eighteen cases of thyroid carcinoma were found in total of 182 patients. The coexistent rate of the Hashimoto's disease with thyroid carcinoma was 9.9% (18/182). Preoperative diagnostic accuracy was only 33.3% (6/18). The 5-year and 10-year survival rates were 88.9% (16/18) and 81.3% (13/16), respectively. Seven received second operation, 2 of them found cancer in the specimens . The 5 years survival rates of the differentiated thyroid cancer (88.2%) was higher than the undifferentiated thyroid cancer (0), but there were no statistical difference due to the small cases (P = 0.167). Two patients had local recurrence and 3 had metastases. They had salvage surgery, which was curative. Three patients with undifferentiated thyroid cancer died of remote metastases. Six patients suffered hypothyroidism. CONCLUSIONS: The preoperation diagnosis accuracy of Hashimoto's disease coexistent with thyroid carcinoma was low. A detail case history,computed tomography (CT), fine needle aspiration (FNA) can help the disease to be diagnosed. The surgical treatment is effective on patients with Hashimoto's disease coexistent with thyroid carcinoma.

[Application of frontal-lateral laryngectomy in laryngeal cancer treatment].

OBJECTIVE: Thirty-eight patients of laryngeal cancer were treated by extended frontal-lateral laryngectomy and the results were evaluated. METHODS: Thirty-eight patients with laryngeal cancer were treated by frontal-lateral laryngectomy and the laryngeal defects were reconstructed by epiglottic flap, bi-pedicle and bi-muscle flap and epiglottic flap plus bi-pedicle and bi-muscle flap from February 1988 to February 2000. There were 29 males and 9 females, ranging in age from 32 to 72 years old. Radical neck dissection was performed in 12 patients. 36 cases belonged to glottic cancer and 2 was superglottic cancer (T2 16, T3 22). RESULTS: The aspiration was light and the majority of cases began to eat in 10-15 days after operation. The decannulation rate was 97.3% (37/38). Wound infection occurred in 3 cases, but pharyngocutaneous fistula was not found. The three and five years survival rates were 86.1% (31/36) and 83.9% (26/31) respectively. CONCLUSION: This procedure present an ideal effect and is worthy to be recommended, but only the indication is limited.