The pathogenesis of Parkinson's disease is closely related to genetic factors. This article has systematically reviewed the research progress of molecular genetic mechanism on Parkinson's disease by focusing on the role of six high-penetrance pathogenic genes (SNCA, LRRK2, PRKN, PINK1, PARK7, and VPS35) and some risk genes (such as GBA1). These genetic variants eventually converge in three core pathogenic biological pathways, including lysosomal-autophagy pathway disorder, mitochondrial quality control disorder and α-synuclein metabolic abnormality. In-depth understanding of these molecular mechanisms is of great significance for the development of targeted therapy and realization of precision medicine for this disease.
Humans ; Parkinson Disease/metabolism* ; alpha-Synuclein/genetics* ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics* ; Genetic Predisposition to Disease ; Protein Kinases/genetics* ; Animals ; Glucosylceramidase/genetics* ; Ubiquitin-Protein Ligases/genetics*

With the rising incidence of colon cancer, several studies have indicated that aquaporin 1 (AQP1) expression is associated with the development of colon cancer. This study aims to elucidate the potential molecular mechanisms between them. Methods: We screened data from The Cancer Genome Atlas (TCGA) database and retrospectively examined AQP1 protein expression in 127 colon cancer patients to analyze the relationship between AQP1 expression and pathological stages, prognosis. We created stable colon cancer cell lines with differential AQP1 expression, the effect of AQP1 expression on the proliferation and migration of colon cancer cells was assessed by in vitro and in vivo studies, and explored potential molecular mechanisms through Western blotting. Results: High AQP1 expression was associated with poorer survival (overall survival [OS], p = .028) in colon cancer patients from the TCGA database. Similarly, retrospective clinical data indicated that high AQP1 expression was associated with reduced disease-free survival and OS (p = .036 and p = .017, respectively). The low-expressing AQP1 colon cancer cells exhibited a decrease in proliferation and migration ability of colon cancer cells compared to the overexpressing AQP1 group (p < .05) in vitro and in vivo. Immunohistochemistry and western blotting experiments validated heightened expression of N-cadherin, vimentin, and claudin- 1 in the tumor tissues of the overexpressing AQP1 group. Conversely, reduced AQP1 expression resulted in decreased expression of claudin- 1. Conclusions: AQP1 correlates with unfavorable prognosis in colon cancer and potentially enhances the proliferation and migration of colon cancer by up-regulating claudin-1 expression.

To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

ObjectiveTo investigate the effects of three traditional Chinese medicine formulas for nourishing kidney Yin on the occurrence of breast cancer， including Zuoguiwan（ZGW）， Liuwei Dihuangwan（LWDHW） and Erzhiwan（EZW）， and to explore their preventive mechanisms from the phagocytic function of macrophages. MethodsTen-month-old post-breeding female mice were randomly divided into the blank group， soy isoflavone group（0.13 g·kg^-1·d^-1， mixed with feed）， ZGW group（2.34 g·kg^-1·d^-1）， LWDHW group（0.56 g·kg^-1·d^-1）， and EZW group（4.68 g·kg^-1·d^-1）. The mice were palpated every 3 d until the age of 18 months， and those with detected lumps were confirmed for tumor development through hematoxylin-eosin（HE） staining， and the incidence of breast cancer in mice was calculated. A total of 40 SPF-grade female SD rats were randomly divided into the blank serum group（physiological saline）， ZGW drug-containing serum group（16.20 g·kg^-1·d^-1of ZGW）， LWDHW drug-containing serum group（3.89 g·kg^-1·d^-1 of LWDHW） and EZW drug-containing serum group（32.40 g·kg^-1·d^-1 of EZW）， each group was orally administered 3 times a day for 5 consecutive days. On the 5^th day， blood was collected from the abdominal aorta 1 h after the last gavage to prepare drug-containing serum. The effect of drug-containing serum with different concentrations on the viability of RAW264.7 cells was assessed by cell counting kit-8（CCK-8）. Taking 20% of drug-containing serum concentration as the research object， its effect on the expression levels of major histocompatibility complex-Ⅱ（MHC-Ⅱ）， CD80 and CD86 on the surface of RAW264.7 cells was detected by immunofluorescence（IF）， the phagocytic function of RAW264.7 cells was examined by flow cytometry， and the levels of interleukin-6（IL-6） and nitric oxide（NO） in RAW264.7 cells in the conditioned medium（CM） co culture system of 4T1 cells were detected by enzyme-linked immunosorbent assay（ELISA） and Griess assay. ResultsAfter prophylactic administration， the tumor incidence rates in the soy isoflavone group（4%）， ZGW group（4%）， LWDHW group（4%）， and EZW group（6%） were lower than that in the blank group（8%）. Compared with the blank serum group， the drug-containing serum of the three nourishing kidney Yin formulas could enhance the expression levels of MHC-Ⅱ， CD80 and CD86 on the surface of RAW264.7 cells， enhance phagocytic ability towards tumor cells， and reduce the content of IL-6 and increase the level of NO（P<0.05， P<0.01）. ConclusionThe three nourishing kidney Yin formulas can reduce the incidence of tumor in mice， the mechanism may be related to activating RAW264.7 cells， increasing their phagocytosis to breast cancer cells， and regulating the secretion of IL-6 and NO.

Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

Objective:To investigate the characteristics and clinical effects of laparoscopic pneumovesical Cohen and laparoscopic Lich-Gregoir ureteral replantations for the treatment of primary obstructive megaloureter (POM) in children.Methods:A randomized controlled study was conducted.The clinical data of 51 children with unilateral POM admitted to the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2023 were collected.Random number table method was used in the selection of surgical methods.They were divided into the laparoscopic pneumovesical Cohen ureteral replantation group (group A, 22 cases) and the laparoscopic Lich-Gregoir ureteral replantation group (group B, 29 cases) according to the surgical method.The anterior-posterior diameter(APD), maximum ureteral diameter and differential renal function parameters on the affected side were measured by color Doppler ultrasound of the urinary system, and compared between and within the two groups before and after surgery.The operation time, blood loss and postoperative intubation time were compared between the two groups.The incidence of postoperative complications such as reflux, bladder spasm, urinary retention and urinary tract infection was recorded.The independent and paired sample t-tests were used for statistical analysis. Results:The operation time and hematuria duration of group B [(125.7±14.2) min, (1.5±0.6) d] were significantly shorter than those of group A [(142.6±14.7) min, (2.8±0.7) d] (all P<0.05). The APD, maximum ureteral diameter, and differential renal function on the affected side of group A were (21.7±7.9) mm, (11.6±3.2) mm, and (28.2±4.9)% before surgery, and (10.3±4.5) mm, (6.0±2.0) mm and (43.8±4.4)% after surgery, respectively.The APD, maximum ureteral diameter, and differential renal function on the affected side of group B were (21.1±5.6) mm, (11.3±4.6) mm, and (30.2±5.5)% before surgery, and (10.2±4.5) mm, (6.6±2.0) mm, and (42.4±5.2)% after surgery, respectively.There was no statistically significant difference in the values of APD, maximum ureteral diameter, and differential renal function before and after surgery between the two groups of children (all P>0.05). However, there were statistically significant differences in the values of APD, maximum ureteral diameter, and differential renal function before and after surgery between the same group of children (all P<0.01). No significant difference was found in intraoperative blood loss, postoperative intubation time, and postoperative complications between the two groups (all P>0.05). Conclusions:Both surgical methods are effective in the treatment of POM in children.Laparoscopic Lich-Gregoir ureteral replantation has advantages of less operation time compared with laparoscopic pneumovesical Cohen ureteral replantation.

Objective:To investigate the efficacy and safety of stanozolol combined with avatrombopag in the treatment of chemotherapy-induced thrombocytopenia(CIT)in patients with relapsed/refractory tumors.Methods:Twenty-five patients with relapsed/refractory CIT admitted to the Hematology Department of Xiyuan Hospital,China Academy of Chinese Medical Sciences between March 2023 to December 2023 were enrolled.These patients received a combined therapy of stanozolol and avatrombopag.The clinical efficacy,onset time,changes in platelet levels and blood cell counts before and after treatment,and adverse reactions of patients were evaluated.Results:The combination therapy demonstrated remarkable efficacy with a total effective rate of 100％.Among the 25 patients,19 achieved complete remission and 6 achieved partial remission.The median onset time was 42.5(range:35-48)days.The average platelet count of the 25 patients increased from(25.73±17.75)× 109/L before treatment to(146.4±49.59)× 109/L after 3 months of treatment,with a statistically significant difference(P＜0.05).18 patients who previously required platelet transfusion were all weaned off platelet transfusion after 3 months of treatment,with a median time to be free from platelet transfusion was 26(range:18-51)days.During the treatment,both neutrophils and hemoglobin exhibited various degrees of elevation.Two patients experienced a slight increase in alanine aminotransferase(ALT)levels,which normalized after treatment with oral hepatoprotective drug.One patient had a PLT increase exceeding 350 ×109/L,and the treatment with avatrombopag was suspended,and aspirin and other drugs were given to prevent thrombosis.No thrombose events or CIT-related bleeding events were observed in all patients.Conclusion:The combination therapy of stanozolol and avatrombopag is significantly effective for treating relapsed/refractory CIT patients,with a high response rate and good safety,making it a suitable clinical treatment option.

Copper is one of the essential elements in the human body,playing various physiological roles.Maintai-ning copper homeostasis is crucial for health.Recent researches have uncovered that copper homeostasis imbalance is closely associated with the occurrence,progression,prognosis,and drug resistance of gynecological malignancies.The employment of copper and its complexes in antitumor therapy has emerged as a promising novel approach,attracting considerable research attention.Based on the relationship between copper homeostasis imbalance and gynecological tumors,this paper provides a concise review of the current status and progress of copper and its complexes in the treat-ment of gynecological tumors.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

Objective To elucidate the impact of chronic kidney disease(CKD)on the clinical outcomes of patients with left main coronary artery disease(LMCAD)undergoing intravascular ultrasound(IVUS)-guided percutaneous coronary intervention(PCI).Methods This retrospective study enrolled consecutive patients with LMCAD who underwent IVUS-guided PCI at Wuhan Asia Heart Hospital between January 2017 and December 2020.Patients were stratified into CKD and non-CKD groups according to the presence of CKD.Clinical data were systematically retrieved from the electronic health record system.Demographic,clinical,and angiographic characteristics were compared between groups.The primary endpoint was major adverse cardiovascular events(MACE),defined as a composite of all-cause mortality,myocardial infarction,and ischemic stroke.Results A total of 325 LMCAD patients[mean age(62.56±9.86)years;73.54％male]were included,with 31 patients(9.54％)in the CKD group.During a median follow-up of 5 years,CKD patients exhibited significantly older age[(70.13±9.77)years vs.(61.77±9.54)years,P＜0.001],higher prevalence of three-vessel disease(64.52％vs.38.10％;P=0.040)and left main bifurcation lesion(45.16％vs.37.76％,P=0.011),greater IVUS-detected calcification burden(P=0.029),and higher median SYNTAXⅡ scores[(34.10(30.30,39.25)vs.26.75(22.42,31.58),P＜0.001)].The cumulative incidence of MACE was significantly higher in the CKD group compared to the non-CKD group(32.26％vs.9.18％,P＜0.001).Univariate Cox regression analysis and Kaplan-Meier survival curves confirmed a 5.877-fold increased risk of MACE in CKD patients(95％CI 2.765-12.494).After adjusting for age and cardiac function,CKD remained an independent predictor of MACE(HR 3.611,95％CI 1.634-7.978).Conclusions LMCAD patients with concomitant CKD present with advanced age,impaired cardiac function,more extensive coronary disease,and severe calcification.The presence of CKD is associated with a significantly worse long-term prognosis.