OBJECTIVE: To observe the effect of acupuncture on chondrocyte autophagy in rats of knee osteoarthritis (KOA) and explore its underlying mechanisms. METHODS: Forty male SPF-grade SD rats were randomized into a blank group, a model group, a suspension group, an acupuncture group, and a combined therapy group, 8 rats in each one. Except the blank group, KOA model was prepared by the injection with papain. The suspension exercise therapy (10 min each time, three times daily), acupuncture (at "Yanglingquan" [GB34], "Zusanli" [ST36], and "Dubi" [ST35] on the right side, 30 min each intervention, once daily) and the combined therapy (the suspension exercise therapy combined with acupuncture) were delivered in the suspension group, the acupuncture group and the combined therapy group, respectively. The intervention of each group was performed continuously for 6 days, and 4 consecutive weeks, at the interval of 1 day. Before and after intervention, Lequesne MG score was assessed in the rats. After intervention, HE staining was adopted to observe the cartilaginous tissue morphology of the right knee joints, and Mankin score was evaluated; the serum levels of interleukin (IL)-1β, IL-6, and tumor neurosis factor-α (TNF-α) were measured using ELISA; the real-time PCR was provided to determine the mRNA expression of collagen protein type Ⅱ(COL2), collagen protein type Ⅹ (COL10), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), and autophagy-regulated protein (Beclin-1) in the cartilaginous tissue of the right knee joint; Western blot was employed to detect the protein expression of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), mTOR, phosphorylated mTOR (p-mTOR) and Beclin-1 in the cartilaginous tissue of the right knee joint. RESULTS: Compared with the blank group, the rats in the model group showed the higher Lequesne MG score (P<0.01), thinner cartilage of the right knee, reduced chondrocytes and disordered arrangement, and higher Mankin score (P<0.01). Besides, in the model group, the serum levels of IL-1β, IL-6 and TNF-α were elevated (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 decreased (P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR increased (P<0.01) in the cartilaginous tissue of the right knee joint. Compared with the model group, in the suspension group, the acupuncture group and the combined therapy group, the Lequesne MG scores were reduced (P<0.01), the cartilage of the right knee was thickened, the arrangement of chondrocytes was improved, and the Mankin scores were lower (P<0.01). Besides, in these intervention groups, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05, P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. When compared with the suspension group and the acupuncture group, in the combined therapy group, the Lequesne MG score was reduced (P<0.01), and the Mankin score was reduced (P<0.05, P<0.01). Besides, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.05), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. CONCLUSION Acupuncture can promote cartilage regeneration of knee joint and autophagy in KOA rats, alleviate inflammation, so as to retard cartilage degeneration, which may be possibly associated with the PI3K/Akt/mTOR signaling pathway.
Animals ; Male ; Acupuncture Therapy ; Proto-Oncogene Proteins c-akt/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/physiopathology* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Signal Transduction ; Rats, Sprague-Dawley ; Chondrocytes/metabolism* ; Humans ; Autophagy ; Acupuncture Points

Objective:To explore the suitable prostate cancer screening mode under the medical community for primary hospitals.Methods:From April 2021 to April 2022, a total of 16007 male population ≥50 years from 9 branches of the medical community of the second hospital of Yinzhou participated in this study. They were divided into four groups according to age with group 1 of 50-59 years old, group 2 of 60-69 years old, group 3 of 70-79 years old, and group 4 of 80 years old and above. Serum tPSA was added to the routine physical examination, and the screening positive patients were referred to the referral hospital for further diagnosis and treatment under the mode of medical community. We proposed multi-parametric MRI (mpMRI) for those with serum PSA ≥4 ng/ml and suspicious lesions should be scored according to PI-RADS V2. The ultrasound-guided transperineal targeted prostate biopsy was performed for those with PI-RADS ≥3 and those with PI-RADS < 3 but tPSA ≥10 ng/ml. The tPSA follow-up examinations were performed every 6 months for tPSA < 10 ng/ml and PI-RADS < 3 points and once a year for tPSA < 4 ng/ml.Results:Among the 16 007 male population ≥50 years, 2 007(12.54%) were found serum PSA ≥4 ng/ml, and 634(31.59%)were referred to the referral hospital through the medical community system. Combining tPSA and mpMRI, 271 patients underwent ultrasound-guided transperineal targeted prostate biopsy. Among them, 162 were finally diagnosed with PCa, with a biopsy positive rate of 59.78%. The detection rate of PCa in all the subjects was 1.01%. According to the pathological grade, 5(3.08%) were in ISUP group 1, 95(58.64%) in ISUP group 2-3, and 62(38.27%) in ISUP group 4-5. There were 102(62.96%), 39(24.07%) and 21(12.96%) with localized, locally advanced or metastatic PCa, respectively. The levels of tPSA in the four groups were (1.13±1.44)ng/ml, (1.77±3.45)ng/ml, (3.27±17.58)ng/ml, and (4.26±11.48)ng/ml, respectively, with statistically significant differences ( P<0.01). The positive number of biopsy in each group was 1 case(0.06%), 56 cases(0.79%), 81 cases(1.36%) and 24 cases(1.82%) respectively, with statistically significant differences ( P<0.01). The number of ISUP 4-5 grades in each group was 0, 17(30.35%), 29(35.80%), and 16(66.67%) respectively, with statistically significant differences ( P<0.01). Conclusions:Based on the medical community system, according to the tPSA screening results of the primary hospitals, it is feasible and effective to refer suspicious patients to the referral hospitals for mpMRI examination, and screen prostate cancer by ultrasound-guided transperineal prostate fusion biopsy.

OBJECTIVES: Tubulointerstitial diseases is one of the common causes of renal dysfunction. Some rare pathological types are easy to be misdiagnosed and missedly diagnosed because of their low prevalence and relatively insufficient understanding, which affects the treatment and prognosis of patients. This study aims to explore clinical manifestations and pathological characteristics of several rare tubulointerstitial diseases, and therefore to improve their diagnosis and treatment. METHODS: A total of 9 363 patients diagnosed by renal biopsy in the Department of Nephrology, Second Xiangya Hospital, Central South University from November 2011 to September 2021 were selected. Six cases of light chain cast nephropathy (LCCN), 2 cases of light chain proximal tubulopathy (LCPT), 1 case of LCCN with LCPT, 4 cases of genetic tubulointerstitial disease, and 6 cases of non-genetic related tubulointerstitial lesion were screened out, and their clinical manifestations and renal biopsy pathological results were collected, compared, and analyzed. RESULTS: Patients with LCCN presented with mild to moderate anemia, microscopic hematuria, and mild to moderate proteinuria. Compared with patients with LCPT, proteinuria and anemia were more prominent in patients with LCCN. Five patients with LCCN and 2 patients with LCPT had elevated serum free kappa light chain. Five patients with LCCN presented clinically with acute kidney injury (AKI). Two patients with LCPT and 1 patient with LCCN and LCPT showed CKD combined with AKI, and 1 LCPT patient presented with typical Fanconi syndrome (FS). Five patients with LCCN, 2 patients with LCPT, and 1 patient with LCCN and LCPT were diagnosed with multiple myeloma. Five patients with LCCN had kappa light chain restriction in tubules on immunofluorescence and a "fractured" protein casts with pale periodic acid-Schiff (PAS) staining on light microscopy. Immunohistochemical staining of 2 LCPT patients showed strongly positive kappa light chain staining in the proximal tubular epithelial cells. And monoclonal light chain crystals in crystalline LCPT and abnormal lysosomes and different morphological inclusion bodies in noncrystalline LCPT were observed under the electron microscope. Six patients with LCCN were mainly treated by chemotherapy. Renal function was deteriorated in 1 patient, was stable in 4 patients, and was improved in 1 patient. Two patients with LCPT improved their renal function after chemotherapy. Four patients with genetic tubulointerstitial disease were clinically presented as CKD, mostly mild proteinuria, with or without microscopic hematuria, and also presented with hyperuricemia, urine glucose under normal blood glucose, anemia, polycystic kidneys. Only 1 case had a clear family history, and the diagnosis was mainly based on renal pathological characteristics and genetic testing. Compared with patients with non-genetic related tubulointerstitial lesion, patients with genetic tubulointerstitial disease had an earlier age of onset, higher blood uric acid, lower Hb and estiated glomemlar fitration (eGFR), and less edema and hypertension. Renal pathology of genetic tubulointerstitial disease presented tubular atrophy and interstitial fibrosis, abnormal tubular dilation, glomerular capsuledilation, and glomerular capillary loop shrinkage. Glomerular dysplasia and varying degrees of glomerular sclerosis were observed. Genetic tubulointerstitial disease patients were mainly treated with enteral dialysis, hypouricemic and hypoglycemic treatment. Two genetic tubulointerstitial disease patients had significantly deteriorated renal function, and 2 patients had stable renal function. CONCLUSIONS Patients with AKI or FS, who present serum immunofixation electrophoresis and/or serum free kappa light chain abnormalities, should be alert to LCCN or LCPT. Renal biopsy is a critical detection for diagnosis of LCCN and LCPT. Chemotherapy and stem cell transplantation could delay progression of renal function in patients with LCCN and LCPT. If the non-atrophic area of the renal interstitium presents glomerular capsule dilatation, glomerular capillary loop shrinkage, and abnormal tubular dilatation under the light microscopy, genetic tubulointerstitial disease might be considered, which should be traced to family history and can be diagnosed by genetic testing.
Humans ; Hematuria ; Immunoglobulin Light Chains/analysis* ; Multiple Myeloma ; Proteinuria ; Nephritis, Interstitial ; Acute Kidney Injury ; Anemia ; Renal Insufficiency, Chronic

Objective To discuss and evaluate the clinical efficacy and safety of sunitinib for patients with advanced renal cell carcinoma and further to analyze the associated prognostic factors.Methods A retrospective analysis was performed in 78 cases with advanced renal cell carcinoma, receiving sunitinib therapy from April 2009 to December 2014.Patients consisted of 53 males and 25 females, with median age of 54 years old, ranged from 25-85 years old.Therapeutic regimen was described as following: 52 cases receiving sunitinib 50.0 mg/d 4 weeks on and 2 weeks off (4/2 regimen), 26 cases receiving 50.0 mg/d 2 weeks on and 1 weeks off (2/1 regimen).The dosage and regimen were adjusted according to the severity of side effects.Efficacy evaluation and drug-related toxicity were based on RECIST version 1.1 and CTCAE version 3.0.Progression-free survival (PFS) and overall survival (OS) were evaluated using the KaplanMeier method.Univariate and multivariate Cox proportional hazards model were used to assess the risk factors of PFS and OS.Results Nineteen cases switched from 4/2 to 2/1 regimen.Attenuated dosage was allowed in 49 cases to ameliorate drug-related toxicities.The most common drug-related toxicities were handfoot syndrome (HFS) in 63 cases (80.8％), diarrhea in 59 cases (75.6％), fatigue in 59 cases (75.6％) and thrombocytopenia in 6 cases (71.8％).The most common grade Ⅲ-Ⅳ toxicities were HFS in 9 cases (11.5％), thrombocytopenia in 6 cases (7.7％) and hypertension in 5 cases (6.4％).In RECIST evaluation, complete response (CR) was not recorded.8 cases (10.3％) achieved partial response (PR) , 59 cases (75.6％) kept stable disease (SD) and 11 cases (14.1％) suffered progressive disease (PD).The objective response rate (ORR) was 10.3％ and the disease control rate (DCR) was 85.9％.The median PFS was 11.0 months and median OS was 21.8 months.Multivariate Cox proportional hazards model showed two independent risk factors for PFS, including number of metastasis organs ≥ 2 and a high ECOG score.One independent risk factor for OS was number of metastasis organs ≥ 2.Conclusions Sunitinib shows encouraging efficacy and safety for patients with advanced renal cell carcinoma.Patients with multiple metastatic organs and poor performance status seems to be high risky of poor prognosis.

Objective To investigate the safety and clinical significance in presurgical application of tyrosine kinase inhibitor (TKI) targeted therapy in high-risk renal-cell-carcinoma patients.Methods TKI targeted therapy was applied to 33 high-risk renal-cell-carcinoma patients from Jun.2010 to Dec.2013,7 cases with paraneoplastic symdromes and 1 with bilateral lesions received surgical treatments.There were 6 males and 2 females in this group with average age of 50 (42-56) years.They were high-risk patients because of renal tumor and vena caval tumor thrombus in 3 cases,renal tumor and vena caval tumor thrombus and hypercalcinemia in 1 case,renal tumors with metastasis to lung and lymph nodes in 2 cases,renal tumor with metastasis to lung and bones in 1 cases,and bilateral kidney cancer in 1 case.The clinical stages included 3 cases of T3aN1M1 and T3bN0M0 respectively,and 1 case of T3bN0M1 and T3aN0M0,respectively.The primary metastasis sites were lymph nodes and lung (3 cases respectively),and another 1 in bone.4 cases suffered from vena cava tumor thrombi with 3 staged Mayo Ⅲ and 1 Mayo Ⅳ.7 cases with paraneoplastic syndromes were contra-indicated for surgery due to poor ECOG performance score (with score 3 in 3 cases and 2 in 4 cases).4 cases received Sorafinib 400mg po bid and the other 4 Sunitinib 50 mg po qd,4 weeks on and 2 weeks off,with duration of 8-12 weeks.Medical therapy ceased 6 to 16 days (median 12 days) before operation.Results Patients with neoadjuvant therapy experienced good toleration.The 7 cases with poor ECOGs improved during medical therapy.The tumor sizes in the bilateral lesions shrunk remarkably.All 7 patients received surgery:3 radical nephrectomies,4 nephrectomies and resections of Vena Caval tumor thrombus,and 1 bilateral lesions underwent nephron sparing surgery.Operations were successful though with mild to moderate adhesion,and the blood loss ranged from 120 to 500 ml,with averaged of 280 ml.Pathologic results were clear-cell renal carcinomas.All incisions were well-healed.4 patients with metastasis continued TKI therapy.All patients were alive without recurrence during the follow-up of 4 to 42 mon.Conclusions Presurgical application of targeted therapy is safe and may increase the opportunity of surgery for some patients with poor general situation,also patients with bilateral lesions may benefit from it for its possibility of nephron sparing.

Objective To investigate the prognostic related factors in patients with renal cell carcinoma(RCC) and bone metastases,treated by targeted therapy.Methods Forty-five patients with RCC and osseous metastases were treated by targeted therapy between June 2006 and April 2013.The mean age was 59 years (range 32-81 years) with 33 male cases and 12 female cases.Twenty-seven cases were diagnosed as RCC accompanied with bone metastases initially,and the median time between the diagnosis of RCC and that of osseous metastasis for the other 18 cases was 12.5 months.All the cases underwent target therapy with sorafenib in 38 cases and sunitinib in 7 cases.Data was retrospectively analyzed and the relationship between several clinical features and overall survival (OS) was examined univariately.The Cox proportional hazards model was then performed multivariately to identify the independent risk factors.According to the independent risk factors,RCC patients with osseous metastases were categorized into high risk group (≤ 1 favorable factors) and low risk group (＞ 1 favorable factors).The median OS in those groups was compared.Results The median OS from the diagnosis of bone metastasis was 19 months,and overall survival was 74.7％ at 1 year,and 32.7％ at 2 year.Clinical features correlated with longer survival in the multivariate analysis were the absence of osseous metastases when initially diagnosed as RCC (HR:2.401,95％CI:1.210-5.699),the resection of primary renal tumor (HR:2.635,95％CI:1.021-6.307) and the absence of extraosseous metastases (HR:2.323,95％CI:1.003-6.221).The median OS of high risk group in 23 patients was 16months.On the other hand,22 patients in the low risk group had a longer median OS with 22 months.There was a significant difference in median OS between the two groups (P＜0.05).Conclusions The three prognostic factors including the absence of osseous metastases when initially diagnosed as RCC,the resection of primary renal tumor and the absence of extraosseous metastases could be favorable factors for RCC patients with bone metastasis treated with target therapy.

Objective To discuss the clinical features and treatment of ureteral obstruction resulted from vena genitalis compression.Methods 2 cases of hydronephrosis resulted from vena genitalis compression were discussed retrospectively,and relevant literatures were reviewed.Both of the 2 patients presenting with mild loin pain,and imaging studies showed hydronephrosis.One patients presenting with left hydronephrosis,and the other showed bilateral hydronephrosis.Imaging study showed ureter obstruction at L3-L4 level.Laparoscopic surgery found vena genitalis crossing and compressing the upper part of the ureter,resulted the upper ureter and pelvis dilation.Laparoscopic excision of vena genitalis were performed on these two cases.Results These patients'symptoms were relieved and hydronephrosis alleviated evidently 3 month after surgery in follow-up.Conclusions Hydronephrosis resulted from vena genitalis compression is a rare clinical manifestation.Classical imaging presents with ureter obstruction at L3-L5 level,at which the vena genitalis crossing the musculi psoas major.Ureter migrates outwards and the upper ureter and pelvis dilate.Pre-operative diagnosis is difficulty,but laparoscopic resection of the vena genitalis to relieve the obstruction of the ureter is recommended.

Objective To evaluate the different expression level of prostate cell carcinoma antigen (PSCA)mRNA in bladder transitional cell carcinoma(BTCC) and normal bladder tissue,additionally analyse the relationship between PSCA mRNA expression level in BTCC and different rs2294008 (C ＞ T) genotypes and various clinicopathological features,including stage and grade.Methods Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was performed on 80 BTCC samples and 38 samples of normal bladder mucosal to measure the expression of PSCA mRNA.Genomic DNA were extracted from tumour tissue to sequence to determine the rs2294008 (C ＞ T) genotypes.Results PSCA mRNA expression was detected in all samples (100％).Tumor samples had significantly higher PSCA expression (M =0.22) than normal samples (M =0.12) (P =0.038).PSCA mRNA expression level was positively correlated with advanced histological grade (G1-2 vs.G3,P =0.001).However no significant difference was detected between patients with superficial tumors (Ta or T1) and those with (≥ pT2)muscle-invasive tumors (P =0.250).There was significantly higher PSCA mRNA expression in T allele carriers than CC homozygous (P =0.001).Conclusions PSCA mRNA expression is related to the BTCC and tumor histological grade,however it is unrelated to tumor stages.PSCA mRNA expression level is higher in patients with T allele carriers than CC homozygous,suggesting T allele may increase PSCA mRNA' s expression.

Objective To develop a nomogram which can accurately predict the disease recurrence risk after the transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder urothelial carcinoma.Methods There were 317 patients in total with newly diagnosed non-muscle invasive bladder urothelial carcinoma from 1998 to 2007 enrolled in this study.The patient's gender,age,smoking history,drinking history,comorbidity of renal failure,time from diagnosis to operation,tumor size,tumor number,tumor grade,and intravesical therapy served as the predictors of the disease recurrence.Every prognosis factor were analyzed and screened through univariate and multivariate Cox proportional hazard regression statistical analysis,and the nomograms that could be used to predict the 3-year and 5-year recurrence probability after the surgery were developed.And the prediction accuracy of the nomogram had been internal validated and calibrated as well.Results Of the 317 patients,the three-year and five-year disease recurrence rates were 36.9％ (117/317) and 43.5％ (138/317),respectively.The patient's gender (RR=0.617,P=0.011),age (RR=1.369,P=0.088),tumor size (RR=1.474,P=0.030),tumor number (RR =1.663,P =0.002),tumor grade (RR =1.880,P =0.000),and comorbidity of renal failure (RR =3.646,P =0.000) had been proved to be the prognosis factors with significantly statistical difference.The predictive accuracy of the nomograms predicting the 3-year and 5-year disease recurrence after the surgery was 75.2％ and 68.3％,respectively.Conclusion The nomograms can provide individualized accurate risk estimations for patients,and therefore it can provide assured proof to formulate the individualizing treatment and follow-up protocol in clinic.

Recently,some researches have been focused on prostate stem cell antigen and related cancers.Researches have reveled that prostate stem cell antigen is overexpressed in prostate cancer,bladder cancer and some malignant tumors in digestive system,and is highly associated with tumour genesis and progress.This review is to show the recent researches on association between prostate stem cell antigen and bladder cancer.