Objective:To investigate the treatment efficacy of adjuvant anti-VEGF/VEGFR targeted therapy in patients with non-metastatic (cM 0) non-clear cell renal cell carcinoma and tumor thrombus (nccRCC-VTT). Methods:This retrospective study enrolled 26 patients who underwent radical nephrectomy combined with inferior vena cava tumor thrombectomy at Peking University Third Hospital from January 2014 to July 2021. Patients were divided into adjuvant therapy group (10 cases) and control group (16 cases)based on the use of postoperative targeted therapy. The distribution of baseline clinical characteristics in the adjuvant therapy group and the control group were as follows: gender (6 males and 4 females in the adjuvant therapy group, 12 males and 4 females in the control group, P=0.66), age (56.2±18.5 years old in the adjuvant therapy group; 54.6±14.5 years old in the control group; P=0.80), BMI(24.0±3.5 in the adjuvant therapy group; 24.3±3.3 in the control group; P=0.80), presence of clinical symptoms (8 cases in the adjuvant therapy group; 15 cases in the control group; P=0.54), tumor laterality(6 cases on the left and 4 cases on the right in the adjuvant therapy group; 6 cases on the left and 10 cases on the right in the control group; P=0.42), location of tumor thrombus (2 cases with renal vein tumor thrombus and 8 cases with inferior vena cava tumor thrombus in the adjuvant therapy group; 2 cases with renal vein tumor thrombus and 14 cases with inferior vena cava tumor thrombus in the control group; P=0.67), ASA classification (2 cases in ASA class 1 and 8 cases in ASA class 2 in the adjuvant therapy group; 2 cases in ASA class 1 and 14 cases in ASA class 2 in the control group; P=0.63), surgical approach (7 minimally invasive surgeries and 3 open surgeries in the adjuvant therapy group; 9 minimally invasive surgeries and 7 open surgeries in the control group; P=0.68), conversion to open surgery (2 cases in the adjuvant therapy group; 2 cases in the control group; P=0.63), operation time [287.5(222.2, 456.0) minutes in the adjuvant therapy group; 344.0(287.8, 482.5) minutes in the control group; P=0.34), blood loss [400.0(250.0, 600.0)ml in the adjuvant therapy group; 575.0(175.0, 800.0)ml in the control group; P=0.63), Clavien-Dindo classification of postoperative complications (8 cases with no postoperative complications, 2 cases with level 1-2 complications, and 0 cases with level ≥3 complications in the adjuvant therapy group; 10 cases with no postoperative complications, 4 cases with level 1-2 complications, and 2 cases with level ≥3 complications in the control group; P=0.68), postoperative hospital stay (8.5 [5.5, 11.5] days in the adjuvant therapy group; 7.5 [6.0, 13.0] days in the control group; P=1.00), maximum tumor diameter[ (9.2±2.7)cm in the adjuvant therapy group; (8.9±3.3)cm in the control group; P=0.81], sarcomatoid differentiation (0 cases in the adjuvant therapy group; 1 case in the control group; P=1.00), perinephric fat invasion (2 cases in the adjuvant therapy group; 7 cases in the control group; P=0.40), tumor necrosis (6 cases in the adjuvant therapy group; 5 cases in the control group; P=0.23), pathological subtype (1 case of PRCC type 1, 6 cases of PRCC type 2, and 3 cases of TFE3 rearrangement RCC in the adjuvant therapy group; 2 cases of PRCC type 1, 10 cases of PRCC type 2, and 1 case each of oncocytic PRCC, TFE3 rearrangement RCC, FH-deficient RCC, and unclassified RCC in the control group; P=0.72), WHO/ISUP nuclear grade (10 cases of grades 3-4 in the adjuvant therapy group; 4 cases of grades 1-2 and 12 cases of grades 3-4 in the control group; P=0.14), invasion of tumor thrombus into the vessel wall (5 cases in the adjuvant therapy group; 5 cases in the control group; P=0.43), T stage (1 case of T 3a, 3 cases of T 3b, 5 cases of T 3c, and 1 case of T 4 in the adjuvant therapy group; 1 case of T 3a, 4 cases of T 3b, 10 cases of T 3c, and 1 case of T 4 in the control group; P=1.00), and positive lymph nodes metastasis(3 cases in the adjuvant therapy group; 0 cases in the control group; P<0.05). The recommended doses for sunitinib, axitinib, and pazopanib are 50mg qd, 5mg q12h, and 800mg qd, respectively. The primary endpoint of this study was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). Statistical analyses were performed using R v4.2.2. Confounding factors were adjusted using propensity score weighting. Results:The median follow-up time for DFS was 29 months in the adjuvant therapy group and not reached in the control group, while median follow-up time for OS was 28 and 26 months, respectively. In the univariate Cox regression analysis, there were no statistically significant difference in the impact of all baseline characteristics and exposure factors on DFS and OS between the two groups. In survival analysis, there were no significant difference between DFS and OS curves of patients in the adjuvant therapy group and the control group (DFS, P=0.62; OS, P=0.74). The median DFS of patients in the adjuvant therapy group and the control group were 17 and 19 months, respectively, while the median OS was 43 and 27 months. After adjusting for confounding factors, the median DFS of patients in the adjuvant therapy group and the control group were 26 and 12 months, respectively, and the median OS remained 43 and 27 months, with no significant difference (DFS, P=0.81; OS, P=0.40). Conclusion:There is currently a lack of definitive evidence for survival benefit from adjuvant anti-VEGF/VEGFR targeted therapy in patients with cM0 nccRCC-VTT after surgery.

BACKGROUNDOveractive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB.

METHODSThis was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated.

RESULTSAt baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy.

CONCLUSIONSWe showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Prospective Studies ; Quality of Life ; Quinuclidines ; therapeutic use ; Solifenacin Succinate ; Tetrahydroisoquinolines ; therapeutic use ; Treatment Outcome ; Urinary Bladder, Overactive ; drug therapy

Objective To find out the current situation of brucellosis infection and exposure status of family members of sheep farmers in the western pastoral areas of Jilin Province,and to provide a reference for control of human brucellosis spreading among family members.Methods On November 2012,Qianguo County was randomly selected using a multi-stage sampling method,and two townships,Chaganhua and Wulantala,were randomly selected in the county; half of the villages were selected from each township; all family members of the sheep farmers in these villages were investigated about their demographic characteristics (sex,age,education),high-risk behavior and information about brucellosis infection by using a questionnaire survey.Based on the principle of informed consent,respondents venous blood samples were collected.Brucellosis was confirmed with serum agglutination test (SAT).The effects of gender,age,education and other demographic data,high-risk behavior and high-risk behavior protection on the prevalence of brucellosis were studied.Results Out of the 403 copies of qualified questionnaires collected,84 people were found infected with brucellosis,and the infection rate was 20.84％ (84/403).Men infection [24.78％ (57/230)] was higher than that of women [15.61％ (27/173),x2 =5.038,P ＜ 0.05].The rates of eight kinds of high-risk behaviors were:helping feeding 86.85％ (350/403),cleaning sheepfold 80.40％ (324/403),holding lamp 71.71％ (289/403),delivering sheep 61.54％ (248/403),vaccinating sheep 53.85％ (217/403),apoblema 47.39％ (191/403),milking 22.08％ (89/403) and slaughtering sheep 14.89％ (60/403).The highest risk behavior was vaccinating sheep[24.40％(53/217)],and the lowest was milking [16.90％ (15/89)].The highest rate of basic protection was delivering a sheep [31.85％ (79/248)],the next was apoblema[27.23％ (52/191)],and the lowest was slaughtering sheep [8.33％ (5/60)].There was no statistical significant difference between brucellosis infection and the eight kinds of high-risk behaviors as well as the basic protective behaviors.Conclusions The prevalence of brucellosis infection among sheep farmers' family members is higher than others.Brucellosis infection-related contact manner is ubiquitous and the level of basic protection is low.We should carry out targeted health education on sheep farming household members to improve their level of protection,so as to reduce the risk of brucellosis infection.

Objective To study the awareness of Brucellosis prevention knowledge and prevalence of risk behaviors among the primary and secondary school students from breeding livestock’s families in Western pastoral areas of Jilin province,and to provide evidence for the prevention and control of Brucellosis.Methods With application of multi-stage random sampling method,a questionnaire survey which including Brucellosis prevention knowledge and risk behaviors was conducted among 209 primary and secondary school students in west part of Jilin province in 2012.Results 105(50.97%)students had heard Brucellosis among 206 students,the older students knew more about Brucellosis than the younger(χ2 =28.80,P=0.00).The M(Q)of the score of the Brucellosis-related knowledge was 8(6.00,9.00),the total passing rate was 28.64%.72(68.61%)students learned Brucellosis from village doctors and acquaintances,only 11(10.51%)students learned it from school;the contact rates of eight kinds of high-risk behaviors were helping feeding 21.84%(62/206),holding lamb 16.50%(58/206),cleaning sheepfold 8.73%(26/206),vaccinating sheep 5.34%(17/206),milking 2.91%(6/206);cleaning apoblema 2.91%(6/206),slaughtering 2.42%(5/206)and delivering lamb 1.94%(4/206);there was no significant difference between the passing rate and the eight kinds of the basic protective behaviors except feeding (P>0.05).Conclusion The level of Brucellosis prevention knowledge is low in Western pastoral areas of Jilin province, and there was a high-risk of contact behavior with sheep and low basic protection rate. It indicates that the education about prevention and control of Brucellosis in the students from breeding livestork’s familes should be strengthened in order to prevent Brucellosis infection.

The overactive bladder syndrome (OAB) is a prevalent condition among adults. Currently, the present treatment is mainly conservative therapy. Antimuscarinic drugs are currently the first-line treatment for OAB. However, many patients experienced insufficient therapeutic benefit and/or unpleasant side effects. Recent advances in the understand-ing of the physiopathology of OAB have driven a huge amount of basic and clinical research into novel pharmacological com-pounds.β3-adrenoceptor agonists are an emerging drug class for the treatment of the OAB. This study reviewed the pharma-cological profile ofβ3-adrenoceptor agonists and discussed the efficacy, safety and tolerability.

Objective To analyze the effect of cyclosporin A(CsA), rapamycin(RPM) and macophenolic acid(MPA) on the co-stimulated lymphocytes, CD28 and CD40, and their production of Th1/Th2 cytokine, IL-2, IFN-γ, IL-4, IL-10 and IL-12. Methods The experimental groups were divided into ①mono-stimulating and co-stimulating groups: CD3 mAb mono-stimulating (group a),CD3 mAb+CD28 mAb co-stimulating (group b), CD3 mAb+CD28 mAb+CD40 L mAb co-stimulating(group c), CD3 mAb+CD28 mAb+CTLA4 mAb co-stimulating (group d). ②CsA groups: 300 ng/ml of CsA was added to group a, b, c and d. ③RPM groups: 300 ng/ml of RPM was added to group a,b, c and d. ④MPA groups:300 ng/ml of MPA was added to group a, b, c and d. The cytokine production was measured by ELISA.Results The co-stimulated CD28 and CD40 Th1/Th2 cytokines production of IFN-γ, IL-2, IL-4 and IL-10 were significantly increased. Compared with group a, IFN-γ increased from (248.91±11.20)ng/ml to (555.08±24.42)ng/ml and (548.19±33.06)ng/ml, IL-2 increased from (29.48±8.61)ng/ml to (1100.82±99.29)ng/ml and (842.23±29.31)ng/ml, IL-4 increased from (32.29±6.76)ng/ml to (116.02±15.03)ng/ml and (147.28±18.07)ng/ml, IL-10 increased from (147.01±10.47)ng/ml to (291.79±12.47)ng/ml and (302.52±35.18)ng/ml,respectively, P＜0. 01. Compared group b with group c, the Th1 cytokines production was decreased.IL-2 and IL-12 decreased (P＜0.05). The Th2 cytokine IL-4 production was increased (P＜0. 05).CTLA4 mAb and three other immunosuppressants, CsA, RPM and MPA, inhibited co-stimulated lymphocyte's both cytokines Th1 and Th2 production. The inhibitory effect of CsA on Th1/Th2 cytokine production was more significant than RPM and MPA did. The co-inhibitory effect of CTLA4 mAb and CsA was observed as well. The increased co-stimulated CD28 and CD40 IL-12 production could be suppressed by MPA. CsA and RPM had no inhibitory effect on the IL-12 production.Conclusions CD28/CD40 co-stimulatory pathway plays the key role in lymphocyte activation and Th1/Th2 cytokine production. CsA, RPM and MPA can inhibit co-stimulated lymphocyte's Th1 and Th2 cytokine production. CsA and CTLA4 mAb have co-inhibitory effect on co-stimulated lymphocyte's Th1/Th2 cytokines production. CD40 L mAb decreases the Th1 cytokines production(including IL-12) and increases the Th2 (mainly IL-4) production, which may be the mechanism of its longevity effect on allograft.

Objective To establish transplantable rat prostate carcinoma and study its relationship to hormone dependency. Methods Six transplantable rat prostate carcinoma lines were established from primary tumors developing in the dorsolateral prostate of F344 rats receiving a combined treatment with 3, 2’-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP). Results Growth in the subcutis of nude mice (ICR-nu/nu) is rapid with a doubling time of approximately 10 days and transplantability is 100%. The histological appearance of the transplanted tumors is very similar to that of the primaries and their structures have not been altered by after 8 passages. Androgen receptor immunohistochemistry revealed all to be negative. Conclusions These data indicate that the model should prove useful for studies of invasion, metastasis, and hormone dependency of prostate carcinomas.

Objective To study the mechanisms underlying this loss of AR expression in rat prostate cancer. Methods The methylation status of the AR gene promoter region in rat prostate cancer and cell lines (PLS10,20,and 30) was investigated by Southern blotting,methylation-specific polymerase chain reaction,and methylation-sensitive single-strand conformation analysis (MS-SSQA). Results AR mRNA expression was not detected in any of the rat prostate cancers or cancer cell lines tested by Northern blot analysis. Higher levels of methylated CpGs were observed in PLS20 than that in PLS10 or 30. Demethylation treatment by 5-aza-2’-deoxycytidine restored AR mRNA expression in PLS20.The CpGs was suggested to be responsible for AR expression in rat prostate cancer,and found to be located-9 and-1 nucleotides upstream of the transcriptional initiation site.All of the examined rat prostate and seminal vesicle cancers demonstrated hypermethylation at these CpG sites. Conclusions These data clearly demonstrate that aberrant hypermethylation in the AR promoter region may play a critical role in AR expression in rat prostate cancers.Loss of AR expression might result in development of hormone-resistant prostate carcinoma.

Objective:To find out the data of the micturitions in healthy young people with the remote & mobile voiding diary monitoring system.Methods:Twenty healthy young people were studied and ten of them were female.The ages ranged from 22 to 35 years(the mean age:27.4 years).The females were 22-33 years old(the mean age:26.4 years) and the males 24-35 years old(the mean age:28.4 years).With the remote & mobile voiding diary monitoring system,their voiding information was collec-ted.Through bluetooth,the voiding information was sent to the patient's intelligent cell phone from the collector,then stored directly by intelligent cell phone and wirelessly transmitted to the workstation in the hospital.All of them completed the voiding diaries for 7 days and the data were analyzed.Results:The average micturition of the young healthy people was 5.6 times(3.4-7.4) per 24 hours,in which 5.3(3.4-7.3) times were in the daytime and 0.3(0-1.3)times in the night.The functional voiding vo-lume was 318 mL(66-642 mL).The mean voiding volume in 24 hours was 1 724 mL(1 152-2 415 mL),in which 1 289 mL(786-2 039 mL) was in the daytime and 435 mL(292-805 mL) in the night.The mean drinking volume was 1 022 mL(453-1 721 mL)in the daytime and 7 mL(0-43 mL) in the night.The nocturia index(Ni)was 1.03,the nocturnal polyuria index(NPi) 26%,and the nocturnal bladder capacity index(NBCi) 0.27.Conclusion:The remote & mobile voiding diary monitoring system can help us get the objective voiding information from young health people for the first time.It is reliable,maneuverable and can be widely used in clinical diagnosis.

Nocturia is one of the most common reasons for interrupted sleep in general adult population.The condition affects both men and women,with an incidence that increases dramatically with age.Nocturia has a negative impact on quality of life,affecting both morbidity and mortality.International Continence Society(ICS) issued a report of terminology standardization in 2002,in which nocturia is defined as waking during the night at least once to urinate.Nocturia is a common complaint in elderly population.Although most cases of nocturia are assumed to be caused by urologic problems,the interacting effects of aging and sleep on renal and urinary function,in fact,cause nocturia in the elderly.Effective diagnosis of the condition is dependent on a clear understanding of its underlying etiology.Multiple factors may cause nocturia,such as behavioral or environmental factors and pathologic conditions.In general,the causes of nocturia fall into three categories:diurnal polyuria,nocturnal polyuria,and low bladder capacity.Careful evaluation of medications and underlying medical conditions is essential for the proper management of nocturia.A voiding diary is necessary to diagnose the syndrome of nocturnal polyuria,which is a common cause of nocturia.Addressing any underlying conditions that contribute to nocturia is the first step in treating the condition.Lifestyle and behavioral changes may provide benefit in some individuals,but for many cases,pharmacotherapy is the best option.Antimuscarinic agents are first-line therapies for overactive bladder and are often used in the management of nocturia.Current treatment options also include desmopressin,a synthetic analog of arginine vasopressin,which can increase urinary osmolality and decrease total urinary volume.The desmopressin therefore increases the length of time until the first nocturnal void and decreases the number of nocturnal voids,the NUV voided,and the percentage of urine voided at night.