Parkinson's disease(PD)is the most common neurodegenerative disease,and Lewy bodies(LBs)is the most typical pathological change.α-synuclein(α-syn),as the main component of LBs,is considered as the pathogenic factor of PD.According to the transmission hypothesis,pathological α-syn can be transported from damaged neurons to normal neurons,leading to pathological misfolding and aggregation of α-syn in recipient neurons,resulting in cascading neuronal damage.According to the hypothesis of gut-brain axis,pathological α-syn can be produced in the intestine,and uploaded to the central nervous system via the vagus nerve.In this paper,the role of α-syn in the pathogenesis of PD is summarized,in order to provide reference for the study of intervention targets of PD.

Objective: To provide scientific evidence for early lung cancer screening, to analyze the incidence of pulmonary nodules among petroleum company staffs in Sichuan-Chongqing Area. Methods: In January 2021 , 6002 petroleum company staffs in Sichuan-Chongqing Area which scanned by low-dose spiral computed tomography (LDCT) of chest in medical examination center in 2020 were retrospectively collected as objects. Their imaging and clinical data were collected. χ(2) test was used to analyze the differences in the detection rates of lung nodules and suspected lung cancer nodules among workers in petroleum company staffs of different genders, ages and types of work. Results: Among the 6002 objects, 3853 (64.2%) were male and 2149 (35.8%) were female, with an average age of (47.25±12.13) years old. A total of 431 cases (7.2%) of pulmonary nodules and 57 cases (0.9%) of suspected lung cancer nodules were detected. 45 cases were followed up with surgical treatment, and 41 cases (91.1%) of lung cancer were diagnosed by postoperative pathology. There were significant differences in the detection rates of pulmonary nodules and suspected lung cancer nodules between different age groups (χ(2)=51.23, 18.81 , P<0.001). The detection rates of pulmonary nodules in the age groups 51-60 years old and ≥61 years old were higher than those in the age groups≤40 years old and 41-50 years old (P<0.05). The detection rate of suspected lung cancer nodules in the age group≥ 61 years old was higher than those in the age groups≤40 years old, 41-50 years old and 51-60 years old (P< 0.05) . And the detection rate of suspected lung cancer pulmonary nodules in oil workers was higher than that of ordinary workers (P<0.05) . Among female objects, the detection rate of pulmonary nodules in oil workers was higher than that in ordinary workers (χ(2)=8.09, P=0.004) . The detection rate of pulmonary nodules in oil workers aged ≥61 years old was higher than ordinary workers (χ(2)=37.94, P<0.001) . Among male objects, the detection rate of suspected lung cancer pulmonary nodules in oil workers was higher than that in ordinary workers (χ(2)=8.42, P=0.004) . The detection rates of suspected lung cancer pulmonary nodules in oil workers aged 51-60 years old and ≥61 years old groups were higher than those of ordinary workers (χ(2)=4.70, 8.74; P=0.030, 0.003) . Conclusion: LDCT is suitable for early lung cancer screening for petroleum company staffs. During the clinical screening process, LDCT should be used as a routine physical examination item for petroleum workers older than 51 years old.
Adult ; Early Detection of Cancer/methods* ; Female ; Humans ; Lung Neoplasms/diagnosis* ; Male ; Mass Screening/methods* ; Middle Aged ; Multiple Pulmonary Nodules/diagnostic imaging* ; Petroleum ; Retrospective Studies ; Tomography, Spiral Computed

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

OBJECTIVE: To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors. METHODS: A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children. RESULTS: Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%. CONCLUSIONS Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.
Child ; Family ; Humans ; Kidney Neoplasms/therapy* ; Progression-Free Survival ; Retrospective Studies

Objective:To investigate the correlations of human leukocyte antigen (HLA)-A, B, C, and DRB1 genotypes with cross-reactivity caused by aromatic antiepileptic-drugs.Methods:A case-control association study was carried out on subjects who accepted treatments/physical examination in our hospitals from September 2016 and September 2020; 31 patients with aromatic antiepileptic drugs (carbamazepine, phenytoin, oxcarbazepine, lamotrigine and phenobarbital)-induced cross-reactivity were enrolled as patient group, 52 tolerant subjects who took the 5 antiepileptic drugs for more than 3 months without cross-reactivity were chosen as tolerant control group, and 500 healthy volunteers were recruited as normal control group. The ethnicity of all patients and controls was Han Chinese. High-resolution genotyping was performed to compare the HLA-A, B, C, and DRB1 genotypes in subjects of the 3 groups. χ2 test or Fisher's exact test were used to analyze the correlations of HLA genes with cross-reactivity caused by aromatic antiepileptic-drugs. Results:The presence of HLA-B*13:01 genotype in the patient group, the tolerant control group, and the normal control group was 45.2% (14/31), 15.4% (8/52) and 14.6% (73/500), respectively. The presence of HLA-B*13:01 genotype in the patient group was significantly higher as compared with that in the tolerant control group and normal control group ( Pc<0.017). No other HLA genotypes were found to be associated with cross-reactivity caused by aromatic antiepileptic-drugs. Conclusion:HLA-B*13:01 is the risk genotype for cross-reactivity caused by aromatic antiepileptic-drugs.

The differences of transitional components and metabolic processes of Huatan Jiangqi Capsules(HTJQ) in rats under normal physiological and pathological conditions of COPD were analyzed by UPLC-Q-TOF-MS. The rat COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. After the normal and COPD model rats were douched with HTJQ, the blood was collected from hepatic portal vein and the drug-containing serum samples were prepared by methanol precipitation of protein. Then, 10 batches of drug-containing serum samples of HTJQ were prepared and analyzed by UPLC serum fingerprint to evaluate the quality and stability of drug-containing serum samples. UPLC-Q-TOF-MS was used to collect the mass spectrometric information of the transitional components. Twenty-eight transitional components of HTJQ in normal rats and 25 transitional components of HTJQ in COPD model rats were identified by UPLC-Q-TOF-MS. Under pathological and physiological conditions, there were not only the same transitional components in rat serum, but also corresponding differences. Further studies showed that there were also differences in the metabolic process of transitional components between the two conditions. In normal rats, most of the metabolic types of transitional components were phase I reactions. In COPD model rats, phase Ⅰ reactions decreased and phase Ⅱ reactions increased correspondingly. With UPLC-Q-TOF-MS technology, the differences of transitional components and the metabolism process of HTJQ in rats under normal physiological and pathological conditions were analyzed. The results showed that types of transitional components and the activity of some metabolic enzymes would be changed in COPD pathological state, which would affect the metabolic process of bioactive components in vivo. It laid a foundation for further elucidating the metabolic process and pharmacodynamic substance basis of HTJQ.
Animals ; Capsules ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacokinetics* ; Mass Spectrometry ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Rats ; Serum/chemistry*

In order to explore the mechanisms underlying the vasoconstriction induced by blockade of inward rectifier Kchannels (K) with BaCl, myogenic tone of isolated rat coronary artery (RCA) was recorded with wire myograph. The dependence of BaCl- induced contraction on intracellular Ca([Ca]) release and extracellular Ca([Ca]) influx was studied by Cadeprivation and restoration. The mechanisms underlying BaCl-induced RCA contraction were investigated with specific inhibitors. BaCl(0.1-1.0 mmol/L) contracted isolated RCA in a concentration-dependent manner and the maximal contraction was (5.69 ± 1.07) mN, nearly equal to contraction induced by 60 mmol/L KCl. The contractions induced by BaClin Ca-free solution and by followed restoration of 2.5 mmol/L Caaccounted for (35.44 ± 6.72)% and (64.56 ± 5.94)%, respectively. Calcium channel blocker nifedipine (0.3 μmol/L), cyclooxygenase inhibitor indomethacin (100 μmol/L), ERK1/2 inhibitor PD98059 (10 μmol/L) and chloride channel blocker niflumic acid (100 μmol/L) pretreatment depressed the BaCl-induced maximal contraction by (87.82 ± 5.43)% (P < 0.01), (73.23 ± 5.47)% (P < 0.01), (75.69 ± 7.94)% (P < 0.01) and (83.24 ± 7.69)% (P < 0.01), respectively. These results demonstrate that BaClinduces vasoconstriction in RCA by enhancing both [Ca]release and [Ca]influx, and suggest that increase of prostanoids synthesis, activation of calcium channels and chloride channels, as well as ERK1/2 pathway may be involved in this process.

Plants from the genus Pyrola are widely distributed in North Temperate zone. The quinones, phenol glycosides, terpenoids, flavonoids and volatile oil compounds have been identified from these plants. The in vivo and in vitro studies have shown that the genus Pyrola plants exhibit a wide range of pharmacological properties, including antioxidant, antitumor, antibacterial, anti-ischemia and anti-inflammatory activities. Based on analysis of the literature of the genus Pyrola plant, this review summarized the research on chemical constituents, pharmacology and quality control in recent years which can provide evidences for further investigation on the genus Pyrola plants.

BACKGROUND:Angiotensin II receptor antagonists have been found to exerct a stronger protective effect on bone than angiotensin converting enzyme inhibitors. OBJECTIVE:To investigate the effect of different concentrations of irbesartan (angiotensin II receptor antagonist) on the differentiation and mineralization of mouse preosteoblasts. METHODS:Mouse preosteoblast cel lines MC3T3-E1 in logarithmic phase were selected and cultured in the osteogenic induction medium containing 0 (control group), 0.001, 0.01, 0.1 mmol/L irbesartan, respectively. Ten days later, the cel differentiation was observed by alkaline phosphatase staining. The mineralization was observed by alizarin red staining after 21 days of culture. mRNA expressions of osteocalcin, alkaline phosphatase and Runt-associated transcription factor 2 in osteoblasts were detected by real-time PCR at 1, 4, 7, 14 and 21 days of culture. RESULTS AND CONCLUSION:The activity of alkaline phosphatase in al the irbesartan groups (0, 0.001, 0.01, 0.1) was higher than that in the control group (P<0.05), which was the most obvious in 0.01 mmol/L. The number and area of calcium nodules in each irbesartan group were significantly higher than those in the control group (P<0.05), especial y in 0.01 mmol/L. Compared with the control group, 0.01 mmol/L irbesartan significantly upregulated the mRNA expressions of osteocalcin, alkaline phosphatase and Runt-associated transcription factor 2 (P<0.05). These results suggest that 0.01 mmol/L irbesartan significantly promotes the differentiation and mineralization of osteoblasts.

Objective To compare the curative effect and short-term benefits of laparoscopic liver resection with open liver resection in elderly patients with malignant liver tumors and medical comorbidities.Methods Patients aged 70 and over who received liver resections for malignant liver tumors between January and October 2015 were enrolled.The perioperative outcomes of 17 patients with laparoscopic approach were matched and compared with those of 34 patients with conventional open approach in a 1:2 ratio.Results There was no significant difference found between the two groups with regard to age,gender,incidence of comorbid illness,hepatitis B positivity,and Child-Pugh grading of liver function.The median tumor size was 3 cm for both groups.The types of liver resection were similar between the two groups with no significant difference in the duration of operation (laparoscopic: 195 min vs.open: 210 min,P=0.436).The perioperative blood loss was 150 mL in the laparoscopic group and 330 mL in the open group (P=0.046) with no significant difference in the number of patients with blood transfusion.The duration of hospital stay was 6 days (3-15 days) for the laparoscopic group and 8 days (5-105 days) for the open group (P=0.005).Conclusion Laparoscopic liver resection is safe and feasible for elderly patients.The short-term benefits of laparoscopic approach proves to be evident for geriatric oncological liver surgery.