Kidney stones are a typical model of pathological mineralization, and the association between local mineralization imbalance and systemic ectopic calcification is complex. This review systematically summarizes three major advances in the field. Firstly, at the molecular level, inflammatory/immune modulation(Th-cell activation), metabolic dysregulation(aberrant calcium-phosphate/lipid metabolism), and epigenetic control(lncRNA-driven osteogenic differentiation)act in concert to drive Randall's plaque formation. Secondly, at the systemic level, nephrolithiasis shares the Klotho pathway with vascular calcification and bone-metabolic disorders, converging on the inhibition of Wnt/β-catenin and related axes, underscoring the global impact of calcium-phosphate homeostatic disruption. Thirdly, in translational medicine, GeoBioMed technologies dissect mineral heterogeneity, AI models predict recurrence risk(AUC=0.87), CRISPR-based interventions [silencing of metastasisassociated lung adenocarcinoma transcript 1(MALAT1)], and biomimetic materials(carbonate-apatite coatings)exhibit significant therapeutic promise. Future efforts should integrate single-cell multi-omics, microbiome modulation, and cross-organ dynamic monitoring to shift the therapeutic paradigm from stone removal to the precise restoration of mineralization homeostasis.

Objective To explore the principles and methods for extracting terminology related to the pathogenesis of cough disease,as well as the standardization issues in constructing the category structure of"pathogenesis-syndrome";To provide references for standardized research on the pathogenesis of cough disease.Methods The principle of defining the pathogenesis of cough disease was based on the physiological dysfunction and pathological characteristics of lung manifestation.Using ontology technology,literature induction,comparative analysis and other methods,with the help of terminology concepts,Clinical Diagnosis and Treatment Terminology in Traditional Chinese Medicine Part 1:Diseases and important ancient books of TCM throughout history related to the pathogenesis of cough disease were sorted,summarized,and extracted.The relationship between the"pathogenesis-syndrome"category of cough disease was analyzed and the structure was constructed.Results Preliminary principles and methods for standardizing the extraction of pathogenesis terminology of cough disease were formulated,including screening scope,inclusion and exclusion criteria,etc.The content of cough disease entries in Clinical Diagnosis and Treatment Terminology in Traditional Chinese Medicine Part 1:Diseases was defined for pathogenesis terminology,and the hierarchical structure of terminology was established to clarify the connotation and extension of terminology,thereby determining the category relationship of terminology and forming a category structure of"pathogenesis-syndrome"mapping relationship.On this basis,by extracting pathogenesis terms of cough disease from important ancient books of TCM throughout history,a category structure table of"pathogenesis-syndrome"for cough disease in TCM was formed.Conclusion On the basis of formulating standardized extraction principles and methods of pathogenesis terminology for TCM cough disease,a research model for the"pathogenesis-syndrome"category structure of TCM cough disease is constructed.This model has the characteristics of systematicity,clear hierarchical relationships,rich connotation of terminology,and extensibility,providing a new research paradigm for pathogenesis research.

Objective To explore the principles and methods for extracting terminology related to the pathogenesis of cough disease,as well as the standardization issues in constructing the category structure of"pathogenesis-syndrome";To provide references for standardized research on the pathogenesis of cough disease.Methods The principle of defining the pathogenesis of cough disease was based on the physiological dysfunction and pathological characteristics of lung manifestation.Using ontology technology,literature induction,comparative analysis and other methods,with the help of terminology concepts,Clinical Diagnosis and Treatment Terminology in Traditional Chinese Medicine Part 1:Diseases and important ancient books of TCM throughout history related to the pathogenesis of cough disease were sorted,summarized,and extracted.The relationship between the"pathogenesis-syndrome"category of cough disease was analyzed and the structure was constructed.Results Preliminary principles and methods for standardizing the extraction of pathogenesis terminology of cough disease were formulated,including screening scope,inclusion and exclusion criteria,etc.The content of cough disease entries in Clinical Diagnosis and Treatment Terminology in Traditional Chinese Medicine Part 1:Diseases was defined for pathogenesis terminology,and the hierarchical structure of terminology was established to clarify the connotation and extension of terminology,thereby determining the category relationship of terminology and forming a category structure of"pathogenesis-syndrome"mapping relationship.On this basis,by extracting pathogenesis terms of cough disease from important ancient books of TCM throughout history,a category structure table of"pathogenesis-syndrome"for cough disease in TCM was formed.Conclusion On the basis of formulating standardized extraction principles and methods of pathogenesis terminology for TCM cough disease,a research model for the"pathogenesis-syndrome"category structure of TCM cough disease is constructed.This model has the characteristics of systematicity,clear hierarchical relationships,rich connotation of terminology,and extensibility,providing a new research paradigm for pathogenesis research.

Calcium oxalate stones are the most common type of kidney stones in China. The injury and death of renal tubular epithelial cells induced by hyperoxaluria or calcium oxalate crystals are the key factors in the formation of calcium oxalate stones. Renal tubular epithelial cell death can provide attachment sites for calcium oxalate crystals, being part of the composition of stones and aggravate tissue damage. Multiple cell programmed death patterns can participate in cell injury and regulate the intersection to achieve multi-level regulation. This article summarized and discussed the relationship between renal tubular epithelial cell programmed death and the mechanism of calcium oxalate stone formation, and the related research of different programmed cell death patterns involved in the pathogenesis of calcium oxalate stones in recent years.

Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter micro-tubule associated homolog 2(JPT2)is a critical molecule in Ca2+mobilization,and its intrinsic mecha-nism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and theJPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca2+mobilization.Tran-scriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the produc-tion of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and in-flammatory polarization via JPT2/PI3K/AKT signaling.

Objective:To evaluate the clinical value of nanopore targeted sequencing (NTS) in pathogens detection in urinary tract by comparing the results of different tests performed on the same urine sample.Methods:The results of NTS and urine culture test collected from 326 patients in the Department of Urology of People's Hospital of Wuhan University from July 2020 to June 2021 were retrospectively analyzed. There were 224 males and 102 females. The average age was (56.88 ± 14.58)years old. χ 2 test and Student’s test and Wilcoxon's sign rank test were used to analyze the differences of the pathogen detection rate, pathogen types results and detection time consuming between NTS and urine culture. The clinical value of the NTS in rapid detection of urinary pathogens was evaluated. Results:Among 326 hospitalized patients, the urinary tract microbes’ detecting rate of NTS was significantly higher than that of urine culture[67.80%(221/326)vs. 23.93%(78/326), χ2=130.25, P<0.01]. The uropathogens detecting rate of NTS was significantly higher than that of urine culture[54.29%(177/326)vs. 23.31%(76/326), χ2=38.95, P<0.01]. The number of urinary tract microbes detected by NTS was significantly higher than that of urine culture ( Z=11.49, P<0.01), the number of uropathogens was significantly higher than that of urine culture ( Z=9.67, P<0.01). The detection time of NTS and urine culture positive samples was (24.29±2.65) h and (49.28±11.30) h, the difference was statistically significant ( t =39.48, P<0.01). The results obtained by using NTS and urine culture were consistent in 135 (41.41%) samples. In 150 (46.01%) samples, NTS could detect the urinary tract microbes while urine culture cannot find, of which 112 cases (34.36%) were uropathogenic. In 27 cases (8.28%), more pathogens were detected by NTS except those from urine culture. In 6 cases (1.84%) re-detecting NTS after antibiotic therapy, the number of reads of primary uropathogen decreased gradually with the growth of colonizing bacteria or opportunistic pathogens appeared in the end. Re-examinations of urine culture could verify the results of NTS detection on admission in 5 cases (1.53%). NTS in 2 cases (0.61%) could cover the uropathogens of subsequent several urine cultures. Conclusions:NTS has the advantages of rapid, sensitive and comprehensive detection of urinary tract infection pathogens. When urine culture is not yet reported or even negative, NTS already has a certain clinical reference value and can be used as an effective supplement to urine culture, which is conducive to the comprehensive judgment of the patient's condition.

Kidney stones are mixed by various inorganic salts and organic matter according to certain rules. The process of crystal nucleation, growth and aggregation is the key step of kidney stone formation. The different crystal structures will bring about the different formation process and physicochemical properties of kidney stones. It is of great significance to study the crystal structures and formation characteristics of kidney stone to clarify the causes of it and prevent the recurrence of it. In this paper, based on the microstructure and crystal structure of kidney stones, the distribution of different crystals and components in kidney stones, the nucleation and growth process of crystal forming kidney stones, and the different treatment methods based on crystal structure are reviewed in recent years.

Objective:To investigate the availability and safety of a domestic disposable digital flexible cystoscope compared with a reusable Olympus digital flexible cystoscope in cystoscopy and removal of double J stent.Methods:From August 2018 to March 2019, patients were enrolled in this prospective, open, multicenter, randomized, parallel positive controlled clinical trial study, which were from department of Urology in Renmin Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University and the First Affiliated Hospital of Guangzhou Medical University. The experimental group and control group were assigned into a 1∶1 ratio by random table method. Inclusion criteria included age≥18 years and have indications for cystoscopy or removal of double J stent. Exclusion criteria included patients having acute genitourinary tract infection, having tuberculous bladder contracture, bladder capacity less than 50ml, having urethrostenosis, female menstrual period, pregnancy and lactation, having difficulty for lithotomy position, having serious cardio-cerebrovascular disease and liver or kidney dysfunction. A domestic disposable digital flexible cystoscope was adopted in the experimental group, whereas a reusable Olympus digital flexible cystoscope was used in the control group. Acceptability of image was defined as primary availability indicator, while success rate of working and performance score were defined as secondary availability indicators and mean operating time was calculated for cystoscopy only and cystoscopy plus removal of double J stent respectively, yet rate of adverse event as well as rate of equipment defects were sorted as safety indicators.Results:A total of 188 cases which were listed in per protocol set completed the clinical trial study successfully. There were 95 cases in the experimental group and 93 cases in the control group. Acceptability of image was 93.68%(89/95) and 96.77%(90/93) respectively in two groups( P=0.52). Success rate of working was 100.00%(95/95) and 98.92%(92/93) respectively in two groups ( P=0.49). Performance score was 14.41±0.93 and 14.56±0.84 respectively in two groups ( P=0.23). Mean operating time (MOT) only for cystoscopy was (15.3±2.6) min and (15.4±3.3)min respectively in two groups ( P=0.93), while MOT for cystoscopy plus removal of double J stent was (21.0±3.2) min and (21.7±3.9) min respectively in two groups ( P=0.69). Rate of adverse event was 8.42%(8/95) and 9.68%(9/93) respectively in two groups( P=0.76). There was no equipment defects in both groups. Conclusions:There is no statistical difference in acceptability of image, success rate of working, performance score, mean operating time for cystoscopy or removal of double J stent, rate of adverse events and rate of equipment defects. A domestic disposable digital flexible cystoscope has shown non-inferiority in the availability and safety compared with a reusable Olympus digital flexible cystoscope.

Objective:To compare the performance and surgical outcomes of domestic single-use digital flexible ureteroscopes with reusable digital flexible ureteroscopes in treatment of upper urinary stones.Methods:A prospective, single-blind, multicenter and randomized controlled study was performed from September 2018 to June 2019. Eligible patients were randomly assigned, in a ratio of 1∶1, to either experimental group or control group. The inclusion criteria for the study were: aged 18-75 years, solitary upper urinary stone with stone size between 0.8 and 2.0 cm and CT value less than 1 400 HU, negative preoperative urine culture and normal renal function. Exclusion criteria included: patients with acute urinary tract infection, intransitable urethral strictures, impassable ureteropelvic junction obstructions, systemic hemorrhagic disease, coagulation function abnormalities or bleeding tendency, severe hypertension or cardiopulmonary insufficiency, severe hip malformation and difficulty in meeting the demand of operation position and pregnant and lactation women. The device used in the experimental group was a domestic single-use digital flexible ureteroscope, and the device used in the control group was an imported Olympus digital flexible ureteroscope. The qualified rate of clinical comprehensive evaluation (including image quality and operational performance), the rate of device failure, the stone-free rate and the occurrence rate of adverse events (including increase in urine red blood cell and white blood cell counts, postoperative hematuria, nausea, vomiting, dizziness, and fever) in the two groups were recorded.Results:A total of 186 eligible study cases were collected from the People's Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University, and the First Affiliated Hospital of Guangzhou Medical University. 90 cases in the final experimental group and 88 cases in the control group completed the trial and were included in the evaluation. There were no statistically significant differences among age [(48.40±11.36) vs. (47.40±12.53)years old, P=0.594], male to female ratio (62/28 vs. 56/32, P =0.874), BMI [(24.8±2.1) kg/m 2 vs. (25.1±2.0)kg/m 2,P =0.331], hydronephrosis (no/slight vs. mild/severe) (62/28 vs. 65/23, P =0.874), stone location and stone size [(12.8±4.7) mm vs. (11.9±5.2) mm, P =0.227]. There were no significant differences in terms of qualified rate of clinical comprehensive evaluation [98.9% (89/90) vs. 100.0% (88/88), P =0.991], lithotripsy success rate [84.4% (76/90) vs. 84.1% (74/88), P =0.888], device failure/defect rate (both 0%), and the incidence of adverse events [50.0% (45/90) vs. 52.0% (51/88), P =0.894]. The highest incidence of adverse events in two groups was the increase of red blood cells and white blood cells of routine urine after operation. There was no serious adverse event in the experimental group and 1 serious adverse event in the control group. Conclusions:There was no significant difference in image quality, device failure/defect rate, lithotripsy success rate, and adverse event rate between single-use digital flexible ureteroscopes and reusable digital flexible ureteroscopes for lithotripsy of upper ureteral and pelvic stones. Domestic single-use digital flexible ureteroscopes have good safety and effectiveness in the treatment and microscopy of upper urinary tract stones.

The formation mechanism of kidney stones is complex. It is generally recognized that abnormal urine conditions or renal tubular epithelial cell damage, together with other factors cause the formation of renal papillary subepithelial calcium plaques (Randall’s plaques) or stone crystals that block the renal tubules (Randall’s plugs), and then oversaturated crystals gathering on Randall's plaque or plug and forming stones. However, there are many pathophysiological changes and manifestations, such as renal papillary anchoring stones, renal papillary crypts, renal papillary tip erosion, and exogenous renal papilla Renal papillary lesions, which may be an early manifestations before the formation of kidney stones. The study of renal papillary calcium plaque is very important for the pathogenesis of kidney stones, as well as the prevention and treatment of patients with stones. By focusing on the development process of Randall plaque theory, the formation and transformation mechanism of Randall plaque, as well as the manifestations and clinical treatment of the above mentioned different types of renal papillary calcium plaque lesions, this article reviewed three aspects of stone formation, including Randall’s plaque, renal papillary lesions with stones, and renal papillary lesions related to stone.