Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

OBJECTIVE: To explore the displacement and pressure distribution of American Chiropractic in a model of third lumbar syndrome based on finite element analysis. METHODS: On March 2021, CT and MRI images of a 23-year-old male patient with right third lumbar syndrome were selected. A 3D stl model was established using Mimics and CATIA, and the data was imported into Hypermesh, Abaqus & ANSYS. The elastic modulus and Poisson's ratio of the affected side material were adjusted to establish its finite element model. Based on the comparison of the operating positions and routines of the American Chiropractic and the lumbar spine oblique pull method, but with differences in the focus and direction of force, the experimental group simulated the American Chiropractic with the healthy side (left side) lying position of the model. The upper endplate of L₃ and the lower part below L₃ twisted accordingly with the body position, we applied a vertical forward thrust of 246 N to the plane formed by the L₄, L₅ spinous processes and L₄ upper articular processes;The control group simulates the oblique pull method of the lumbar spine, requiring the model to lie on the healthy side (left side), fix the upper endplate of L₄, and perform a horizontal rotation along the longitudinal axis of L₃ vertebral body. At this time, the contact force in the upward direction is also set to 246 N. Compare the displacement and stress differences between the L₁-L₅ intervertebral bodies, intervertebral discs, articular processes, and transverse process muscles in two intervention models. RESULTS: ① Under safe load conditions, a test force of 246 N was applied to the model, and the maximum vertebral displacement occurred on the right side of the L₃ vertebral body (1.197 mm) after manual intervention in the control group. The vertebral displacement between L₁-L₅ induced by manual intervention in the experimental group was smaller than that of the control group's manual intervention (P<0.05). ② The maximum vertebral body stress occurred on the right side of the L₃ vertebral body after manual intervention in the control group (98.425 MPa). The stress on each vertebral body formed by the experimental group's manual intervention was lower than that of the control group's manual intervention (P<0.05). ③The maximum intervertebral disc stress occurred on the right side of the L_2,3 intervertebral disc (6.282 MPa) after manual intervention in the control group. ④ The maximum joint process stress occurred on the right side of the L₄ upper joint process after manual intervention in the experimental group (1.587 MPa). The joint process stress on the left side below L₁ and the left side above and below L₂ induced by manual intervention in the experimental group was lower than that of the control group (P<0.05). ⑤The maximum stress on the intertransverse process muscle was observed at the right lateral L₃ process end (31.960 MPa) of L_3,4 in the control group after manual intervention. The stress on the L_2,3 and L_4,5 segments of the intertransverse process muscle induced by manual intervention in the experimental group was lower than that of the control group's manual intervention (P<0.05). CONCLUSION The mechanical feedback of the L₁-L₅ vertebral body, the lower left side of the articular process L₁, the upper and lower left side of the articular process L₂, and the L_2,3 and L_4,5 segments of the transverse process muscle in the model indicates that performing American Chiropractic for the treatment of third lumbar transverse process syndrome can accurately hit the target pain point and allow the patient's tissue to form a low stress and low tension state after manual operation, thereby reducing the possibility of tissue damage caused by hypertonia after intervertebral joint movement, making it relatively safe. The application of American Chiropractic will be a new supplement to the traditional treatment plan for third lumbar transverse process syndrome.
Humans ; Finite Element Analysis ; Male ; Lumbar Vertebrae/physiopathology* ; Biomechanical Phenomena ; Young Adult ; Manipulation, Chiropractic ; Adult ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

Background and objective Lung cancer is the malignant tumor with the highest incidence rate and the heaviest disease burden in China.In recent years,lung cancer has shown a high incidence trend,seriously affecting the health of the population.In this paper,we analyze the characteristics of lung cancer incidence in 2019 and the trend of incidence rate from 2010-2019 in the tumor registration area of Gansu province,in order to provide a reference basis for the development of lung cancer prevention and control strategies in Gansu province.Methods By analyzing the cases of lung cancer incidence in the tumor registration area of Gansu province in 2019,we calculated the incidence rate,medium incidence rate,world in-cidence rate and other related indexes;we used Joinpoint to calculate the annual percentage change(APC)for trend analysis.Results In 2019,a total of 3757 new cases of lung cancer were reported in Gansu province,accounting for 14.96%of all new malignant tumors.The incidence rate,medium incidence rate and world incidence rate and world rate of lung cancer were 40.52/105,25.78/105,25.86/105;and the cumulative rate of 0-74 years old,and the truncation rate of 35-64 years old were 3.23%,40.03/105,respectively.The incidence of lung cancer rises with age,and is high in the age group of 40 years and above,and the incidence peaks in the male and female populations in the group of 75 years and above,and the group of 80 years and above,respectively.The crude incidence rate of lung cancer in the tumor registration area of Gansu province from 2010-2019 showed an overall increasing trend,and the rate of increase was relatively fast,with an APC 5.39%(P<0.05);Separately,accord-ing to gender,urban and rural areas,the incidence of lung cancer in all populations showed an increasing trend,and the APC of male,female,urban and rural populations were 4.98%,6.39%,6.26%,and 4.64%,respectively(all P<0.05).According to the trend analysis of lung cancer incidence rate by age group,only lung cancer incidence in the age group of 65 years and above increased at an annual average rate of 4.15%(P<0.05).Conclusion The incidence rate of lung cancer in the tumor registration area of Gansu province from 2010 to 2019 shows a rising trend year by year,and there are differences in the incidence of lung cancer in people of different genders,regions and age groups,so comprehensive prevention and control work should be carried out for the key populations of lung cancer incidence.

Objective To investigate the effect of dexmedetomide on oxygen glucose deprivation/reperfusion(OGD/R)myocardial cell injury.Methods H9c2 cardiomyocytes were cultured in vitro and divided into control group(routine culture),model group(OGD/R treatment),experimental-L,-M,-H groups(treated with 1,5 and 10 μmoL·L-1 dexmedetomidine after oxygen glucose deprivation/reperfusion).Apoptosis was detected by flow cytometry;the levels of glutathione peroxidase(GSH-PX),superoxide dismutase(SOD)and lactate dehydrogenase(LDH)were detected by enzyme-linked immunosorbent assay;and Fe2+levels were detected by FerroOrange fluorescent probe.Results The apoptosis rates of control group,model group,experimental-L,-M,-H groups were(4.11±0.35)％,(27.57±2.36)％,(20.52±1.43)％,(14.17±1.55)％,(8.47±0.89)％,respectively;GSH-PX were(26.75±3.14),(126.68±11.42),(98.74±9.23),(73.15±8.02),(45.85±4.80)mU·mL-1,respectively;SOD were(1.59±0.11),(7.52±1.13),(6.12±0.74),(4.97±0.54),(2.35±0.69)ng·mL-1,respectively;LDH were(13.42±1.53),(152.15±18.94),(103.15±12.45),(64.59±7.81),(27.85±3.42)ng·mL-1,respectively;Fe2+were level(20.26±2.93),(63.85±6.44),(52.17±4.58),(40.15±4.12),(27.48±3.08)mmol·L-1,respectively.There were statistically significant differences between control group and model group(all P＜0.05);the model group was compared with experimental-L,-M,-H groups,and the differences were statistically significant(all P＜0.05).Conclusion Dexmedetomidine can alleviate myocardial cell injury induced by OGD/R by regulating iron metabolism.

The occurrence and development of tumors are closely related to the body's immune function.It has been confirmed that immunotherapy plays a role in the treatment of various cancers.Some traditional Chinese medicines can control the growth and metastasis of tumors by enhancing anti-tumor immunity.Even in the immunosuppressive tumor microenvironment,traditional Chinese medicine can exert anti-tumor effects by upregulating immune responses.Further research on the regulation of the immune mechanisms by traditional Chinese medicine will provide new insights into how traditional Chinese medicine controls tumor growth and metastasis and help improve its effectiveness in the clinical treatment of various cancers.This article aims to provide a theoretical reference for the role of immunoregulation in tumors,summarize its mechanisms in tumors,and traditional Chinese medicine intervention research in tumors for the prevention and treatment of tumors with traditional Chinese medicine.

Objective:To explore the incidence and mortality of digestive system cancers, and the trend of the disease burden attributed to different risk factors in population in China.Methods:Data were obtained from the GLOBOCAN 2020 and the Global Burden of Disease Study in 2019 databases and only the data from the Chinese population were included. Using Excel 2019 and R 4.2.1 software, indicators including age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life year (DALY) rate and its rate of change were used to illustrate the disease burden of digestive system cancers attributed to different factors and their trends.Results:In 2020, the ASIR of digestive system cancers in China was 83.00/100 000, and the ASMR was 63.80/100 000. The numbers of digestive system cancer cases and deaths increased with age, and more cases and deaths occurred in men than in women in all age groups. The age-standardized DALY rate of esophageal cancer, gastric cancer and liver cancers showed decreasing trends in China from 1990 to 2019 (rate of change: -45.26%, -46.87%, and -65.63%, respectively), whereas the age-standardized DALY rate of pancreatic cancer, colorectal cancer and gallbladder and biliary tract cancer showed increasing trends (rate of change: 67.61%, 30.52%, and 7.21%, respectively). The trend of the mortality rate was consistent with the DALY rate. Compared with the age-standardized DALY rate attributed to behavioral factors, the annual proportion of the age-standardized DALY rate attributed to metabolic factors to the total age-standardized DALY rate of esophageal cancer, liver cancer, pancreatic cancer, and colorectal cancer increased from 1990 to 2019. There was no significant change in the rank of age-standardized DALY rate of gastric cancer, liver cancer, pancreatic cancer, and gallbladder and biliary tract cancer attributed to different risk factors in China from 1990 to 2019, but the rank of certain attributed risk factors for the age-standardized DALY rate of esophageal cancer and colorectal cancer moved ahead (esophageal cancer: high BMI; colorectal cancer: low milk intake, and low whole-grain intake).Conclusions:The incidence and mortality of digestive system cancers was serious in China in 2020, and the annual proportion of the disease burden of digestive system cancers attributed to metabolic factors increased from 1990 to 2019. The rank of attributed risk factors for several digestive system cancers changed significantly.

As a key epigenetic regulator, histone deacetylases (HDACs) play a crucial role in cancer development. Small molecule HDAC inhibitors have been shown to inhibit tumor proliferation and induce apoptosis, attracting significant research attention. In this study, we designed and synthesized a series of novel saccharin derivatives as HDAC inhibitors. Biological experiments demonstrated that the target compound 9a exhibited superior HDACs inhibition activity to vorinostat and demonstrating promising in vitro and in vivo anti-tumor activity against triple-negative breast cancer (TNBC). All animal experiments in this study were performed in strict accordance with the protocols approved by the Ethical Committee of School of Pharmaceutical Sciences in Shandong University (Approval No. 230094). This work represents an initial exploration of developing saccharin-based HDAC inhibitors, and the active compound 9a could serve as a lead compound for further study.

Objective:To investigate the therapeutic effect of Ningmitai Capsules(NMT)on chronic prostatitis/chronic pel-vic pain syndrome(CP/CPPS)and its action mechanism.Methods:We equally randomized fifteen 6-8 weeks old male Wistar rats into a sham operation,a model control and an NMT group,and established a CP/CPPS model in the rats by intra-prostatic injection of complete Freund adjuvant(CFA).We treated the rats in the sham operation and model control groups by injection of aseptic phosphate buffer saline(PBS)and 50 μl complete Freund adjuvant(CFA),respectively,into the ventral lobe of the prostate followed by gavage with purified water from the second day after surgery,and those in the NMT group with 50 μl CFA injected into the ventral lobe of the prostate followed by gavage with 3 ml NMT suspension at 400 mg/kg/d from the second day after surgery.After 4 weeks of treatment,we killed the animals and collected the serum and prostatic tissue samples for evaluation of the severity of prostatitis by histopathological grading of chronic prostatitis through HE staining,determination of the mRNA expressions of inflammatory factors by real-time quantita-tive PCR,measurement of the activities of related antioxidant enzymes with testing kits,and detection of the expressions of the related targets in the signaling pathways by Western blot.Results:Histopathological examination revealed different degrees of inflammatory cell infiltration in the mesenchyme,inflammatory vacuoles,irregularly shaped acini in the model control group,with a significantly higher inflammation score than in the sham operation group(P＜0.05),and reduced infiltrating lymphocytes,inflammatory vacuoles and inflammation score in the NMT group compared with those in the model controls(P＜0.05).Compared with the rats in the sham operation group,the model controls showed remarkably up-regulated expressions of IL-1 β,IL-6,IL-10,IL-17A,TNF-α and IFN-γ(P＜0.05),decreased contents of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)(P＜0.05),and increased content of malondialdehyde(MDA)(P＜0.05).Compared with the model controls,the rats treated with NMT exhibited markedly reduced expressions of IL-1β,IL-6,IL-10,IL-17A,TNF-α and IFN-γ(P＜0.05),increased contents of SOD,CAT and GSH-Px(P＜0.05),decreased content of MDA(P＜0.05),up-regulated expressions of nuclear factor red 2-related factor 2(n-Nrf2)and heme oxygenase-1(HO-1)(P＜0.05),and down-regulated expression of NF-κB P-P65(P＜0.05).Conclusion:NMT plays anti-oxidation and anti-inflammation roles in the pathogenesis of CP/CPPS,possibly by activation of Nrf2 and suppression of NF-κB signaling pathways.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.