Based on the discussions in the The Inner Canon of Yellow Emperor （《黄帝内经》）， it is proposed that in the course of the disease， "bind" represents the initial stage of pulmonary nodules， while "accumulation" represents the final form. In terms of the pathogenesis， "two colds interacting" represented by "body cold" and "cold fluid retention" are the prerequisites for the formation of pulmonary nodules， while "disorder of qi" represented by "fainting" is the core of the formation. The specific manifestation is the disturbance of pivot of shaoyang （少阳） or shaoyin （少阴）， resulting in a complex of cold and heat， and then phlegm and stasis are suddenly generated and further formed into nodules. Therefore， the treatment principle should be to regulate the cardinal mechanism， dissolve phlegm and blood stasis. Depending on the complex degree of cold and heat， it is suggested to use Chaihu Guizhi Decoction （柴胡桂枝汤）， Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）， or Chaihu Xianxiong Decoction （柴胡陷胸汤） for disturbance of shaoyang pivot， while for shaoyin pivot dysfunction， modified Mahuang Fuzi Xixin Decoction （麻黄附子细辛汤） or Shengjiang Powder （升降散） can be used.

Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

[Objective] To explore the expression of Nectin-4 in invasive bladder urothelial carcinoma (BUC) tissue and its clinical significance, so as to provide reference for clinical diagnosis and treatment of BUC. [Methods] Nectin-4 expression in 60 cases of invasive BUC and 40 cases of chronic inflammation of bladder mucosa was detected with immunohistochemical staining (IHC) and RNAscope.The results of the two methods were analyzed and compared, and the relationship between the two methods and the clinicopathological characteristics of invasive BUC was discussed.The correlation between the protein expression of Nectin-4 in BUC tissues, human epidermal growth factor receptor 2 (Her-2) and programmed death factor ligand 1 (PD-L1) was analyzed. [Results] The positive protein expression rates of Nectin-4 detected by IHC were 78.33%(47/60) and 17.50% (7/40) in the invasive BUC group and inflammatory group, respectively, while the positive mRNA expression rates of Nectin-4 detected by RNAscope were 83.33% (50/60) and 12.50% (5/40), respectively.The Kappa values of Nectin-4 in the invasive BUC group and inflammatory group were 0.732 and 0.610, respectively, with general consistency.The protein expression of Nectin-4 in invasive BUC was correlated with muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The mRNA expression of Nectin-4 in invasive BUC was correlated with max tumor diameter, muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The high expression of Nectin-4 in invasive BUC was positively correlated with the expression of Her-2 (P=0.002), but not with the expression of PD-L1 (P>0.05). [Conclusion] Nectin-4 is highly expressed in invasive BUC, and is usually associated with the pathological parameters of poor prognosis.Detection of Nectin-4 expression will help to guide clinical diagnosis and treatment.

Objective To screen items of the Clinical Aided Decision Scheme for Stroke Simultaneous Treatment of Disease,Pulse and Syndrome;To provide reference for the formulation and improvement of the scheme.Methods The Delphi method was used to distribute two rounds of questionnaires to 60 experts in cerebropathy or neurology across the country.Statistical analysis was performed on the questionnaire results of the scheme's items,including the disease names,etiology and pathogenesis,syndrome characteristics,rules and regulations,representative prescriptions,acupuncture and other therapies,and preventive care.Results Totally 42 and 50 valid questionnaires were collected.The experts reached the consensus for the importance of etiology and pathogenesis,rules and regulations,acupuncture and other therapies,and preventive care.In the section on syndrome characteristics,items with low relevance or causing ambiguity were removed.Items that were no longer used in modern times and different prescriptions with the same name were removed from the representative prescriptions.The names of syndromes,rules and regulations were unified.Conclusion The experts generally reached the consensus for the importance of the Clinical Aided Decision Scheme for Stroke Simultaneous Treatment of Disease,Pulse and Syndrome.However,there are still some limitations that require further study and discussion.

Objective:To evaluate the efficacy of cyclophosphamide(CYP)at different doses in repli-cating the symptoms of interstitial cystitis/bladder pain syndrome(IC/BPS)in an animal model,thereby providing an experimental basis for understanding the pathophysiology of IC/BPS and assessing treatment strategies.Methods:Twenty-eight female Sprague-Dawley rats aged seven weeks were divided into four groups:Group a(25 mg/kg CYP),group b(75 mg/kg CYP),group c(125 mg/kg CYP),and group d(a control group).The rats were injected intraperitoneally with either CYP or saline solution.Evalua-tions included urine spot tests,von Frey filament pain threshold tests,urodynamic examinations,and his-tological assessments.Results:The study found that the 25 mg/kg CYP dosage significantly outperformed higher doses in simulating bladder dysfunction and inflammatory responses while minimizing the impact on the rats'physiological functions.Specifically,urine spot area,group a showed a significant reduction in urine spot area compared with the control group(P＜0.05),while groups b and c did not show signifi-cant differences.Pain threshold:The von Frey filament test indicated increased visceral pain in group a,aligning closely with IC/BPS patient symptoms,without a significant increase in urination frequency.Urodynamic assessments:Group a exhibited decreased bladder compliance and reduced maximum bladder capacity(P＜0.05),with no significant differences in baseline bladder pressure and maximum detrusor pressure across all groups.Histological analysis:Hematoxylin-eosin(HE)staining revealed that bladder tissue in group a had moderate inflammatory reactions,whereas groups b and c showed severe inflamma-tion and tissue damage,correlating with the higher doses of CYP.Furthermore,the urine spot tests and von frey filament tests provided quantitative data supporting the model's reliability,urine spot count,group a had an average urine spot count of(15±3)spots,significantly higher than the control group's(5±2)spots(P＜0.01).Nociceptive score:Group a nociceptive score increased to 0.5±0.1,indica-ting heightened pain sensitivity compared with the control group 0.10±0.05(P＜0.01).Conclusion:The 25 mg/kg CYP demonstrated significant advantages in simulating the key features of non-ulcerative IC/BPS,summarizing the main aspects of the human condition,including persistent visceral pain and mild inflammatory reactions in bladder tissue.These findings offer substantial experimental support for drug development and treatment research in IC/BPS and provide new insights into the complex patho-physiology of the disease.

To investigate the initial experience of coated metal ureteral stent(CMUS)for treatment of pelvic lipomatosis induced hydronephrosis(PLH).The clinical and follow-up data of 8 patients who were diagnosed as PLH treated with CMUS in Peking University People's Hospital from August 2018 to February 2021 were retrospectively analyzed.Inclusion criteria included:Imaging evidence of excessive adipose tissue around the bladder in the pelvic cavity,bladder elevation in an"inverted pear shape",and bladder wall thickening;Cystoscopy indicated follicular hyperplasia of bladder mucosa and biopsy pathology indicated glandular cystitis;Unilateral or bilateral hydronephrosis and ureteromegaly.Exclusion criteria included:Ureteral atresia;Recurrent obstruction of the bladder outlet.Preoperative baseline data included age,gender,serum creatinine,pelvis width and ureteric stent symptoms questionnaire(USSQ)score.Intraoperative data included the location and length of ureteral stenosis observed by retrograde urography.Postoperative follow-up data included serum creatinine,pelvis width,and USSQ score.In the study,8 patients(11 sides)with PLH were all male,with an average age of(38.7±8.6)years.Uni-lateral hydronephrosis was found in 5 cases and bilateral hydronephrosis in 3 cases.Preoperative mean serum creatinine was(90.0±10.3)μmol/L,and the mean renal pelvis width was(3.0±1.5)cm.The lower ureteral stricture was found in all cases,and the mean stricture length was(1.9±0.9)cm.Before operation,3 patients had ureteral Double-J stents,with USSQ scores of 97.0,68.0 and 100.0,respectively.Five patients underwent retrograde CMUS stenting,and 3 patients retrograde and antegrade.At the last follow-up,the average serum creatinine was(82.0±11.1)μmol/L and the mean renal pel-vis width was(1.9±0.5)cm,which were significantly lower than those before operation(t=3.12,P=0.02;t=3.23,P=0.02).In the 3 patients with Double-J stent before surgery,the USSQ scores were 87.0,62.0 and 89.0,respectively,which were significantly improved after CMUS stenting.The average follow-up time was(10.0±6.3)months.During the follow-up,1 patient developed CMUS re-lated symptoms,and no stent-associated infection and stent encrustation were found.In one case,the stent migrated to the bladder 3 months after operation,and the hydronephrosis disappeared after 3 months follow-up.CMUS stenting for treatment of PLH has certain efficacy and safety,which can explore a new therapeutic method for the long-term treatment of PLH.

Objective:To evaluate the safety and efficacy of transtobturator urethral sling operation in the treatment of male stress urinary incontinence.Methods:A retrospective analysis was conducted on the clinical data of 13 male patients with stress urinary incontinence who underwent transvaginal sling procedure at Peking University People's Hospital from June 2011 to July 2024. The patients' average age was (71.6±5.4) years. Among them, 9 patients had undergone radical prostatectomy, and 4 had undergone transurethral resection of the prostate (TURP). Of the 13 patients, 7 had moderate urinary incontinence, and 6 had severe urinary incontinence. The median daily number of urine pads used by the 13 patients before surgery was 5 (3, 8), and the median score of the Incontinence Quality of Life Questionnaire (I-QOL) was 16 (12, 28). The median score of the Male Stress Urinary Incontinence Grading Scale (MSIGS) was 2 (2, 3). All the 13 patients underwent transvaginal sling procedure. The patients were placed in the lithotomy position, and the urethral bulb was dissected anatomically beneath the scrotum. The sling was guided by a needle and pulled out through the obturator foramen, and placed over the urethral bulb. The sling was tightened and the tension adjusted to fully suspend the urethra. A urinary catheter was left in place for 1-7 days after surgery. The patients' postoperative daily use of urine pads, scores of the I-QOL and MSIGS, and postoperative complications were followed up.Results:Postoperative follow-up ranged from 2 to 139 months, with a median follow-up time of 12 months. Of the 13 patients, 2 were cured, 9 had improved and 2 had no significant improvement. The number of diapers used per day by patients postoperatively was 1 (1, 4) pieces, the I-QOL score was 75 (46, 82), and the MSIGS score was 1 (0, 2), which were all significantly improved compared to preoperative values ( P<0.01). Among the 6 severe stress urinary incontinence patients who were followed up, the number of diapers used per day was significantly reduced compared to preoperative values[ 2(1, 5) vs. 8(7, 8) pieces], and the I-QOL score was significantly improved [ 60(35, 70) vs. 12(10, 16) ], while the MSIGS score was significantly lower [ 2(1, 3) vs. 3(2, 4) ]. Among the 7 moderate stress urinary incontinence patients, the number of diapers used per day was significantly reduced compared to preoperative values [1 (0, 1) vs. 4 (4, 5) pieces], and the I-QOL score was significantly improved [ 80(75, 82) vs. 21(18, 30) ], while the MSIGS score was significantly lower [ 0 (0, 1) vs. 2 (2, 3) ]. The symptoms of 1 patient were not significantly improved after the surgery, and were improved after Virtue sling suspension 3 years later. Conclusions:The use of transtobturator urethral sling operation for the treatment of moderate to severe male stress urinary incontinence has shown clear efficacy, with a low incidence of postoperative complications.

OBJECTIVE: To assess health related quality of life (HRQOL) in patients with kidney stones and to predict risk factors for reduced HRQOL in the patients by the Chinese version of Wisconsin stone quality of life questionnaire (C-WISQOL). METHODS: The patients with renal stones admitted to Peking University People ' s Hospital from July 2020 to June 2021 were prospectively enrolled. The inclusion criteria included the patients with renal stones aged 18-80 years and sufficient Chinese language foundation, and the exclusion criteria included the patients with internal ureteral stents, malignant tumors, sepsis, etc. Demographic data and clinical data related to kidney stones were collected, and the C-WISQOL and the short form 36 health survey (SF-36) questionnaire completed by the patients was recorded. C-WISQOL included four domains (D): emotional impact (D1), social impact (D2), stone-related impact (D3) and vitality impact (D4). Cronbach ' s α coefficient was used to verify the internal consistency of C-WISQOL, Spearman ' s rho coefficient was used to verify the criterion validity between C-WISQOL and SF-36 questionnaire, confirmatory factor analysis was used to verify the structural validity, convergent validity and discrimination validity of C-WISQOL, and univariate and multivariate analyses were used to explore the risk factors leading to the decline of HRQOL in the patients with kidney stones. RESULTS: The study included 307 patients with kidney stones, of whom 212 (69.1%) were male, with a mean age of (51.9±13.5) years, and a mean body mass index (BMI) of (25.4±3.6) kg/m². 160 (52.1%) patients were complicated with metabolic syndrome (MS), 202 (65.8%) had history of calculi, 217 (70.7%) had calculi related symptoms, 53 (17.3%) had bilateral renal calculi, 82 (26.7%) had ureteral calculi, 199 (64.8%) had hydronephrosis, 78 (25.4%) had renal insufficiency, and urinary tract infection (UTI) was found in 168 patients (54.7%) with an average diameter of (15.6±5.9) mm. The mean total score of C-WISQOL questionnaire for all the patients was (94.9±13.7) points, D1 was (27.2±4.2) points, D2 was (23.8±3.7) points, D3 was (27.0±3.6) points, and D4 was (10.1±1.9) points. The Cronbach ' s α coefficient of the total score of C-WISQOL questionnaire was 0.968 and the four dimensions ranged from 0.860 to 0.898. The Spearman' s rho co- efficient between C-WISQOL and SF-36 total score was 0.564, and the Spearman' s rho coefficient between dimensions was 0.684-0.901, indicating that C-WISQOL had good internal consistency and criterion validity. Confirmatory factor analysis showed that C-WISQOL had good structural validity, convergent validity and discrimination validity. Univariate analysis showed that the patients with MS (OR=1.607, P < 0.001), calculi related symptoms (OR=1.268, P < 0.001), bilateral kidney stones (OR=1.900, P < 0.001), combined with ureteral calculi (OR=1.018, P < 0.001), accompanied by hydronephrosis (OR=1.685, P < 0.001), and UTI (OR=1.275, P < 0.001) were risk factors for decreased HRQOL in the patients with kidney stones, and multivariate analysis showed that the patients with MS (OR=1.475, P < 0.001), calculi related symptoms (OR=1.546, P=0.043) and UTI (OR=1.646, P=0.005) were independent risk factors for HRQOL decline in the patients with renal calculi. The t-test results showed that C-WISQOL scores were significantly higher in the patients without MS, stone-related symptoms and UTI than those in the patients with associated risk factors (P < 0.001). CONCLUSION C-WISQOL the questionnaire can be used to evaluate the HRQOL of patients with kidney stones with good reliability. The combination of MS, stone-related symptoms and UTI were independent risk factors for HRQOL reduction in the patients with renal stones.
Humans ; Quality of Life ; Kidney Calculi/psychology* ; Surveys and Questionnaires ; Middle Aged ; Male ; Adult ; Female ; Risk Factors ; Aged ; Prospective Studies ; China/epidemiology* ; Adolescent ; Aged, 80 and over ; Language ; Young Adult

【Objective】 To explore the clinical features and treatment outcomes of female urethral carcinoma so as to improve the awareness and prognosis of this rare malignant disease. 【Methods】 Clinical data of 8 cases of female urethral carcinoma treated during Jan. 2012 to Dec.2022 at the Department of Urology of Peking University People’s Hospital were retrospectively analyzed. The patients underwent urodynamic tests, cystourethroscopy and pathological biopsy to confirm the diagnosis. Traditional radical surgery was performed in 5 cases, and radical surgery for lower urethral cancer with bladder preservation was performed in 3 cases. 【Results】 The patients aged 36 to 68 years, with a mean of 53.75 years. Urinary obstruction, lower urinary tract symptoms and urethral masses were common manifestations. Urodynamic tests indicated bladder outlet obstruction. After surgical treatment, radical surgery for lower urethral cancer with bladder preservation showed advantages over traditional radical surgery in terms of intraoperative bleeding, operation time and postoperative hospital stay. 【Conclusion】 Female primary urethral carcinoma is rare but invasive. Early diagnosis and radical surgery are crucial for improving the prognosis. Radical surgery for lower urethral cancer with bladder preservation has better treatment outcomes and postoperative quality of life compared to traditional radical surgery. For such patients, symptoms should be closely monitored and timely diagnosis and treatment should be performed.

Adenosine triphosphate (ATP) regeneration systems are essential for efficient biocatalytic phosphoryl transfer reactions. Polyphosphate kinase (PPK) is a versatile enzyme that can transfer phosphate groups among adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, and polyphosphate (Poly P). Utilization of PPK is an attractive solution to address the problem of ATP regeneration due to its ability to use a variety of inexpensive and stable Poly P salts as phosphate group donors. This review comprehensively summarizes the structural characteristics and catalytic mechanisms of different types of PPKs, as well as the variations in enzyme activity, catalytic efficiency, stability, and coenzyme preference observed in PPKs from different sources. Moreover, recent advances in PPK-mediated ATP regeneration systems and protein engineering of wild-type PPK are summarized.
Adenosine Triphosphate/metabolism* ; Adenosine Monophosphate ; Polyphosphates/metabolism* ; Catalysis ; Regeneration