BACKGROUND: Urolithiasis is a widespread disease with a high prevalence worldwide. This study aims to evaluate the disease burden of urolithiasis and its trends from 1990 to 2021 globally, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. METHODS: The numbers and age-standardized rates (ASRs) of incidence, disability-adjusted life years (DALYs), and mortality of urolithiasis were extracted from GBD 2021 to represent the disease burden. Joinpoint regression analyses were conducted to assess the temporal trends in the burden of urolithiasis. The male-to-female ASR ratio indices were used to evaluate sex disparities. Additionally, we explored the relationship between the ASR ratio and the sociodemographic index (SDI). RESULTS: The total numbers of incidence, DALY, and mortality of urolithiasis were 105,983,780 cases (95% uncertainty interval [UI] = 88,349,356-128,645,155 cases), 693,444 cases (95% UI = 567,765-850,490 cases), and 17,672 cases (95% UI = 13,932-21,241 cases), respectively, in 2021. There is an increasing trend in the number of these measures globally, whereas the ASRs have decreased over the past 30 years. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were significantly higher in males than in females in 2021. The sex disparities in the age-standardized DALY rate (ASDR) and ASMR of urolithiasis were negatively correlated with the SDI. In 2021, the ASIR of urolithiasis was 964.70 (95% UI = 801.26-1175.09) per 100,000 people in China, which is much lower than the global average (1242.84 [95% UI = 1034.94-1506.99] per 100,000 people). Compared with the global average, a more pronounced decline in ASIR was observed in China from 1793.16 (1446.0-2235.14) in 1990 to 964.70 (801.26-1175.09) per 100,000 people in 2021. CONCLUSIONS Urolithiasis poses a significant healthcare burden worldwide. More robust global and national strategies are warranted to address the prevention and treatment, especially in low SDI countries and regions.
Humans ; Urolithiasis/mortality* ; Male ; Female ; Incidence ; Global Burden of Disease ; Disability-Adjusted Life Years ; Adult ; Middle Aged ; Risk Factors ; Sex Factors

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

[Objective]To explore the efficacy of Solifenacin in the treatment of children with idiopathic overactive bladder(OAB).[Methods]The study included 67 children with idiopathic OAB treated in the urology clinic of our hospital from March 2022 to March 2023.After at least 2-week-long behavioral therapy showed no significant therapeutic effect,52 of the cases in the trial group were given oral Solifenacin 5 mg once daily and the other 15 cases in the control group con-tinued the behavioral therapy.The cases in trial group were subdivided into OAB-dry group(27 cases without urinary in-continence)and OAB-wet group(25 cases with urinary incontinence).The 3-day micturition diary,OAB Symptom Scores(OABSS)and the adverse reactions were recorded and analyzed before,at Weeks 2,4,8 and 12 after the treat-ment.[Results]Of all the 67 cases who completed a 3-month follow-up,44 were cured including 41 in the trial group and 3 in the control group,4 presented with adverse reactions.After the 3-month follow-up,the OABSS declined markedly in trial group than in control group(Z=4.524,P<0.001);the cure rates in trial group and control group are 78.8%and 20%respectively,with significant difference(χ2=15.367,P<0.001).At each follow-up,we found increased mean voided vol-ume(F=9.707,P<0.001),reduced mean voiding frequency during daytime(F=3.837,P=0.009)and decreased voiding urgency(χ2=482.835,P<0.001).After the 3-month follow-up,the cure rates in OAB-dry group and OAB-wet group are 81.5%and 76%respectively,with no significant difference(χ2=0.234,P=0.629).[Conclusions]In children with idiopath-ic OAB,oral Solifenacin 5 mg once daily could significantly increase mean voided volume,reduce mean voiding frequency during daytime,relieve symptoms of urinary urgency and lead to fewer adverse reactions,but is not significantly effective for the treatment of urinary incontinence in OAB-wet children.

CD96 is a transmembrane glycoprotein belonging to immunoglobulin superfamily that mainly expresses on NK cells and T cells.Previous studies have shown that CD96-CD155 axis inhibits proinflammatory effects of Th9 cells to maintain immune homeostasis.In mice tumor models,CD96-CD155 axis suppresses anti-tumor effects of NK cells and CD8+T cells.CD96 deficiency or blockade significantly inhibits tumor growth and prolongs survival of tumor-bearing mice,thus CD96 is considered a potential immuno-suppressive molecule(i.e.immune checkpoint).However,research on human CD96 function is still unclear,with limited knowledge on role of human CD96 in tumor microenvironment,further in-depth exploration is needed.This review summarizes discovery and development,molecular structure,and regulatory roles of CD96 in inflammatory responses and tumor immunity.

ObjectiveTo explore the potential molecular mechanism of Qizhu Kang'ai Formula （芪术抗癌方， QZKAF） for the treatment of colorectal cancer （CRC）. MethodsNetwork pharmacology was used to analyze the active ingredients and targets of QZKAF for CRC， and analyze the key targets of QZKAF for the treatment of CRC by gene function annotation （GO） and Kyoto Encyclopedia of Genomes （KEGG） pathway enrichment analysis. Molecular docking was applied to predict the binding activity of the core active ingredients to the key targets. A orthotopic transplantation tumor mice model of CRC was established to validate the key targets of QZKAF for CRC obtained from network pharmacology analysis. Forty-eight mice were randomly divided into the sham operation group， the model group， the 5-fluorouracil （5-Fu） group， and the QZKAF low-， medium-， and high-dose groups， with 8 mice in each group. Except for the sham operation group， the remaining groups underwent colon cancer orthotopic transplantation tumor modeling. The 5-Fu group was given 30 mg/kg of 5-Fu by intraperitoneal injection once every 3 days on the alternate day after modeling， while the QZKAF low-， medium-， and high-dose groups were given 2.925， 5.85， and 11.7 g/（kg·d） of QZKAF by gastric gavage， respectively， and the sham-operation group and the model group were gavaged with 0.1 ml/10 g of normal saline every day， all for 21 days. The in situ tumors mass and the number of liver metastases were compared between the groups. The pathological changes of colon tumor tissues were observed by HE staining， and the protein expression of protein tyrosine phosphatase nonreceptor type 1 （PTPN1）， vinculin， integrin subunit αν， integrin subunit β3， and E-cadherin were detected in colon tumor tissues by Western blot. ResultsNetwork pharmacology screening yielded that the top six core active ingredients of QZKAF intervening in CRC were quercetin， kaempferol， apigenin， luteolin， baicalein and ursolic acid. There were 212 targets of action， and the ranked top three were prostaglandin endoperoxide synthase 1 （PTGS1）， prostaglandin endoperoxide synthase 2 （PTGS2）， and PTPN1， which may be the key targets of QZKAF in the treatment of CRC. These key targets were significantly enriched mainly in phosphatidylinositol 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， focal adhesion and adhesion junction. Molecular docking results： except for PTGS1 with better binding activity to quercetin， kaempferol， and apigenin （binding energy ≥-7.0 kcal/mol）， PTGS1 showed strong binding activity to lignans， baicalein， ursolic acid， as well as PTGS2 and PTPN1 to the six core active ingredients （binding energy ＜-7.0 kcal/mol）. Experimental validation results： the protein expression of PTPN1， vinculin， integrin subunit αν， integrin subunit β3 in the colon tumor tissues of mice in the model group significantly increased， and the expression of E-cadherin significantly decreased compared to those in the sham operation group （P＜0.05）. Compared to those in the model group， the mass of the in situ tumors was reduced， and the number of hepatic metastasis nodules decreased in the high- and medium-dose QZKAF groups （P＜0.05）； the expression levels of PTNP1， vinculin， integrin subunit αν， integrin subunit β3 and E-cadherin in all QZKAF groups and 5-Fu group showed different degrees of retracement， and the changes of the indicators in all QZKAF groups showed a certain degree of dose-dependence （P＜0.05）. HE staining showed that the nuclei of tumor cells in the model group were mostly schizophrenic， and there were different degrees of nuclear fragmentation of tumor cells in all QZKAF groups with more in the medium- and high-dose groups. ConclusionQZKAF could inhibit the growth of in situ tumors and liver metastasis of CRC. Its mechanism might be related to the regulation of tumor cell-cell and tumor cell-extracellular matrix adhesion by PTPN1.

Tumor microenvironment activatable therapeutic agents and their effective tumor accumulation are significant for selective tumor treatment. Herein, we provide an unadulterated nanomaterial combining the above advantages. We synthesize a perylene diimide (PDI) molecule substituted by glutamic acid (Glu), which can self-assemble into small spherical nanoparticles (PDI-SG) in aqueous solution. PDI-SG can not only be transformed into nanofibers at low pH conditions but also be reduced to PDI radical anion (PDI^·‒), which exhibits strong near-infrared absorption and excellent photothermal performance. More importantly, PDI-SG can also be reduced to PDI^·‒ in hypoxic tumors to ablate the tumors and minimize the damage to normal tissues. The morphological transformation from small nanoparticles to nanofibers makes for better tumor accumulation and retention. This work sheds light on the design of tumor microenvironment activatable therapeutics with precise structures for high-performance tumor therapy.

Nosiheptide is a typical thiopeptide antibiotic displaying potent activity toward various drug-resistant strains of Gram-positive pathogens.Although nosiheptide lacks in vivo activity, and good water-solubility with a series of uncontrollable analogues, which may limit its clinical application, glycosylated analogues may overcome problem of low activity and may improve its druggability.In search of novel glycosylated nosiheptide producers, we applied a genome mining strategy that identified Actinoalloteichus sp.AHMU CJ021 that contains all genes required.However, despite the presence of a predicted glycosyltransferase, glycosylated derivatives of nosiheptide were not detected, after following one strain many compounds (OSMAC) strategy and heterologous expression of a regulatory protein NocP.Nevertheless, nosiheptide produced by this strain was remarkably pure, and further experiments were conducted to improve its production by optimization of the culture medium.Under optimal conditions, 58.73 mg/L nosiheptide was produced, representing an almost 6-fold improvement compared to the original fermentation medium.Therefore, we consider Actinoalloteichus sp.AHMU CJ021 a suitable potential candidate for industrial production of nosiheptide, which provides the basis for solving the problem of nosiheptide structural analogues.

Objective:To explore the risk factors involved in gastritis, gastric intraepithelial neoplasia (GIN) and gastric cancer in Shihezi area.Methods:A total of 7 110 Han nationality patients who underwent gastroscopy at the First Affiliated Hospital of Shihezi University School of Medicine from January 2012 to December 2016 were selected as the research subjects. The data of patients were obtained through medical records and questionnaires. After excluding diseases related to esophagus and duodenum, a total of 4 429 cases were included in the retrospective analysis. Of which, 4 249 were gastritis, 93 were GIN, and 87 were gastric cancer. χ2 test, rank-sum test or Fisher exact probability method were used to analyze the differences of various factors in gastritis, GIN and gastric cancer. Univariate and multivariate logistic regression analysis were used to screen the risk factors for gastritis progression to GIN and gastric cancer. Results:χ2 test and rank sum test showed that there were statistically significant differences in gender, age, history of digestive diseases and distribution of Helicobacter pylori ( HP) infection among the groups of gastritis, GIN and gastric cancer ( P<0.05). The proportion of HP infection decreased gradually with the disease severity. Multivariate logistic regression analysis showed that male ( P<0.001, OR=2.251, 95% CI: 1.461-3.470), elderly ( P<0.001, OR=4.829, 95% CI: 2.241-10.409), a family history of gastric cancer ( P=0.002, OR=3.227, 95% CI: 1.537-6.774) and a history of digestive diseases ( P=0.034, OR=1.644, 95% CI: 1.037-2.607) were independent risk factors for gastritis progression to GIN. Male ( P<0.001, OR=3.254, 95% CI: 2.026-5.225), middle-aged ( P=0.022, OR=2.688, 95% CI: 1.153-6.265) and elderly ( P=0.002, OR=4.734, 95% CI: 1.750-12.807) were independent risk factors for gastritis progression to gastric cancer. In stratified analysis to exclude age and gender, smoking ( P=0.028, OR=4.060, 95% CI: 1.160-14.202) was found to be a risk factor for gastritis progression to GIN in young adults, and obesity ( P=0.032, OR=3.869, 95% CI: 1.121-13.356) was found to be a risk factor for gastritis progression to gastric cancer in women. Conclusion:The degree of HP infection in gastric tissues is negatively correlated with the severity of gastric diseases, suggesting that HP infection may be an early event inducing gastric cancer. Male, the elderly, people with a family history of gastric cancer and a history of digestive diseases, and young smokers in Shihezi are more likely to develop GIN, and male, middle-aged, elderly, and obese women are at increased risk of gastric cancer.

Diabetic nephropathy is a microvascular complication in the advanced stage of diabetes. About 20%-40% of patients with diabetes will progress to diabetic nephropathy. And worldwide, diabetic nephropathy has become the leading cause of end-stage renal disease. Animal model is a useful tool to study the pathogenesis and treatment of diabetic nephropathy. Currently, the commonly used diabetic nephropathy models all simulate partial characteristics of human diabetic nephropathy in different degrees of pathophysiology. However, the research on diabetic nephropathy has not achieved considerable progress. The main obstacle is that there is no effective animal model that can fully simulate all the characteristics of human diabetic nephropathy. In this paper, the animal models of diabetic nephropathy were reviewed from the aspects of modeling mechanism, pathophysiology, their advantages and disadvantages.

The β-sheet peptides can be self-assembled to form different supramolecular solids. The supramolecular solid can be linked to a wide range of functional domains, for example, with cell adhesion sequences, signal domains, and vaccine epitopes to form complex nanostructures, which can be widely used in biomedical fields. In this paper, we mainly reviewed the self-assembly of peptides using β-folding secondary structure to form nanostructures, and discussed the application of nanostructures in drug delivery and tissue engineering.