Smoothened (SMO) is a member of sonic hedgehog homology (SHH) signaling pathway. It plays a key role as a bridge between patched-1 (PTCH-1) and Gli. Aberrant SHH expression can be detected in various malignant tissues, and the expression in pancreatic cancer stem cells is higher apparently. SHH signals are closely associated with self-duplication of cancer stem cells, formation of tumor vessels as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show potential to inhibit activity of SHH signaling, and arrest the growth as well as metastases of tumors. Recently, a few of SMO antagonists have been studied in phase I clinical trials and some are in phase II, meanwhile, phase I or II trials of SMO antagonists to treat pancreatic cancer are performed currently. As the classical SMO antagonist, cyclopamine is extracted from a medicinal plant. Perhaps researchers may be able to determine more effective SMO-targeting drugs from herbal medicines in the future.

Objective To investigate the clinical value of detection of fluorescence quantitative PCR in detection of HBV DNA and HBV markers.Methods 653 hepatitis B patients in our hospital from 2013 April to 2013 December were selected.First ELISA method using HBV-M model for qualitative detection of the blood samples,the detection order:Hepatitis b virus surface antigen (HBsAg),Hepatitis B surface Antibody(HbsAb),Hepatitis B e Antigen(HbeAg),hepatitis Be antibody(HbeAb),hepatitis B core antibody(HbcAb);Then the FQ-PCR method for the quantitative detection of HBV-DNA,different HBV-m model test results were compared..Results Big 3 this world[1(+)、3 (+)、5 (+)model]and[1 (+)、3 (+)model ]of the HBV-DNA positive rate was 97.97%,94.74% was significantly higher than that in other mode(P<0.05).Big 3 this world[1(+)、3(+)、5(+)model]HBV-DNA expression level is the highest(5.59 ×106 ±2.42 ×105 )copies/mL was significantly higher than that in other mode(P<0.05).Conclusion Combined with qualitative and quantitative detection of HBV-DNA HBV-M,which is of great value to clinical early diagnosis and therapy.

Objective: To investigate the quality of life among patients with occupational pneumoconiosis in Jinhua City, Zhejiang Province, so as to provide insights into improving the quality of life among patients with occupational pneumoconiosis. Methods: Patients with occupational pneumoconiosis in Jinhua City from 2009 to 2021 were retrieved from the National Occupational Disease and Health Risk Factors Monitoring Information System. Participants' demographics, diagnosis of pneumoconiosis, stage of pneumoconiosis, pulmonary function and medical expense were collected through questionnaire surveys, and the quality of life was measured using a Chinese version of the Short-Form Health Survey (SF-36). The quality of life was descriptively analyzed among patients with occupational pneumoconiosis by disease stage, pulmonary function, expense for disease diagnosis and treatment and educational level. Results: A total of 244 patients with occupational pneumoconiosis were enrolled, including 225 men (92.21%). The participants had a mean age of (75.20±9.42) years, and mean duration from dust contact to pneumoconiosis onset of (13.11±9.89) years. The scores for physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health were (64.03±31.22), (45.14±44.22), (56.34±26.60), (40.80±19.80), (59.14±17.35), (68.41±19.67), (47.03±44.08) and (61.15±17.06) points among patients with occupational pneumoconiosis, which were all lower than the national constant (P<0.05). Lower scores were measured for physical functioning [(31.17±23.40) points], bodily pain [(45.21±19.50) points] and vitality [(47.00±20.70) points] among patients with stage Ⅲ occupational pneumoconiosis, for physical functioning [(32.27±24.24) points], role-physical [(12.88±30.70) points], bodily pain [(37.44±20.43) points], general health [(14.76±17.17) points], vitality [(38.79±19.33) points], social functioning [(53.33±17.08) points], role-emotional [(9.09±26.71) points], and mental health [(53.21±17.25) points] among occupational pneumoconiosis patients with severe pulmonary function damages, and for physical functioning [(30.97±27.40) points], bodily pain [(37.77±24.34) points], general health [(19.10±18.62) points], vitality [(38.39±23.78) points], social functioning [(55.89±21.00) points] and mental health [(55.35±20.35) points] among occupational pneumoconiosis patients that had personal payments for pneumoconiosis diagnosis and treatment expenses exceeding 30% of annual household incomes, while higher scores were measured for physical functioning [(66.36±17.33) points] and role-physical [(59.09±45.10) points] among occupational pneumoconiosis patients with an educational level of high school and above (all P<0.05). Conclusions The quality of life was low among occupational pneumoconiosis patients in Jinhua City from 2009 to 2021. Stage of pneumoconiosis, pulmonary function, medical expenses and educational level were identified as factors affecting the quality of life among occupational pneumoconiosis patients in Jinhua City.

Objective: To investigate the disease burden of occupational pneumoconiosis from 2009 to 2021 in Jinhua City, Zhejiang Province, so as to provide insights into formulating occupational pneumoconiosis prevention and control measures. Methods: Data on occupational pneumoconiosis in Jinhua City from 2009 to 2021 were collected through Occupational Disease and Health Hazard Monitoring Information System including demographic characteristics, disability level, age, pneumoconiosis type and stage, and analyzed years live dwith disability (YLD), years of life lost (YLL) and disability adjusted life years (DALY) by different genders, pneumoconiosis stages, pneumoconiosis types, ages and disability levels. Results: A total of 244 occupational pneumoconiosis cases were diagnosed in Jinhua City from 2009 to 2021, of which 225 cases were male, accounting for 92.21%. The median age of onset was 44.50 (interquartile range, 23.00) years. There were 229 deaths, with a median age of 78.00 (interquartile range, 13.00) years. The DALY was 3 791.88 person-years, YLD was 2 428.21 person-years (64.04%) and YLL was 1 363.67 person-years (35.96%). The YLD was 3 647.8 person-years in men, which was higher than 144.08 person-years in women (P<0.05). The YLD of asbestosis cases was lower than that of silicosis, coal workers' pneumoconiosis and other pneumoconiosis (P<0.05). The YLL was not statistically significant in the stage and type of occupational pneumoconiosis (P>0.05). The YLD was higher among cases at ages of less than 40 years, and lower among cases at ages of 60 to 69 years and 70 years and over (P<0.05); the YLL was lower among cases at ages of 70 years and over (P<0.05). The cases with second/third level of disability had the highest YLD, followed by the cases with fourth/fifth level of disability, and the cases with sixth/seventh level of disability had the lowest YLD (P<0.05). Conclusions The disease burden of occupational pneumoconiosis in Jinhua City from 2009 to 2021 is mainly induced by disability, and the disease burden caused by silicosis is the highest. With the progress of pneumoconiosis stages and disability levels, the life loss continues to increase.

Objective: To construct air quality health index (AQHI) in Jinhua City, Zhejiang Province based on the exposure-response relationship between air pollutants and years of life lost (YLL), and evaluate the health risk associated with air quality. Methods: Air pollutants and meteorological data in Jindong District and Wucheng District of Jinhua City from 2014 to 2021 were collected through Jinhua Environmental Monitoring Center and Jinhua Meteorological Bureau. Non-accidental death data of residents during the same period was collected through Zhejiang Chronic Disease Monitoring Information Management System. The exposure-response relationship between major air pollutants and YLL was analyzed using a generalized additive model (GAM), and major pollutants were screened for calculating AQHI. The exposure-response relationship between AQHI and YLL was analyzed using GAM. Results: The results of single-pollutant model analysis showed that the lagged effect of PM2.5 on YLL was the largest at lag of 1 day, and the effect of SO2 on YLL was the largest on the same day. The results of dual-pollutant model analysis showed that the impact of PM2.5 on YLL was statistically significant when other pollutants were included at a lag of 1 day, and the impact of SO2 on YLL was statistically significant when NO2 was included on the same day (all P<0.05). The average daily mass concentration of O3 exceeded the standard by a relatively high rate of 42.27% from 2014 to 2021. Based on the analysis results of single-pollutant and two-pollutant models, excessive pollutant condition and relevant research findings, PM2.5, SO2, NO2 and O3 were selected as the major pollutants for calculating the AQHI. The median AQHI value of 1.40 (interquartile range, 1.13) from 2014 to 2021. According to the AQHI classification standard, 94.55% was the time was at low risk, and 4.93% of the time was at medium risk. With an increase in AQHI by one interquartile range, the YLL among the entire population, males, females, <65-year-old and ≥65-year-old populations would increase 6.21, 3.26, 6.46, 4.24 and 10.57 person-years, respectively. Conclusions The air quality health risk in Jinhua City was low at most of the time from 2014 to 2021. An increase in AQHI was associated with an increased risk of YLL among population.

Objective: To understand the health risk of drinking water in rural areas of Jinhua and to provide evidence for water sanitary management in rural areas. Methods: Totally 2 032 samples of drinking water in rural areas of Jinhua were collected from 2016 to 2018. According to GB/T 5750-2006 Standard Examination Methods for Drinking Water,five chemical carcinogens（As,Cd,Cr6+,CHCl3 and CCl4）and twelve non-carcinogenic chemicals（Pb,Hg,Se、CN-、F-、NO3-、Al、Fe、Mn、Cu、Zn and NH3-N）were detected. The health risk assessment in rural drinking water was conducted by United States Environmental Protection Agency（USEPA）model. Results: The total health risk,total carcinogenic risk and total non-carcinogenic risk of rural drinking water caused by the seventeen chemicals were 34.8×10-6/a,34.80×10-6/a and 6.65×10-9/a,respectively. The carcinogenic risk of five chemical carcinogens accounted for 99.98% of the total health risk,and the carcinogenic risk of Cr6+ accounted for 89.95% of the total health risk. The total health risk of the fully processed,partially processed and unprocessed water samples were 31.68×10-6/a,34.78×10-6/a and 34.77×10-6/a,respectively. The total health risk of finished water and peripheral water were 34.79×10-6/a and 34.82×10-6/a. Conclusion The health risk of drinking water in rural areas of Jinhuacaused by chemicals is low. The hexavalent chromium has the highest health risk and need more attention to be paid on.

Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

Purpose: Breast cancer (BC) is a predominant malignancy globally, surpassing lung cancer in terms of diagnostic frequency, with an escalating incidence rate in recent decades.Recent studies have investigated the role of protein kinase C zeta (PRKCZ) in diverse cellular processes in cancer biology. In this study, we evaluated the association between PRKCZ and deleterious outcomes in BC and elucidated the mechanisms underlying its expression in breast carcinoma. Methods: The correlation between PRKCZ and survival rates of patients with BC was investigated using The Cancer Genome Atlas database. The methylation status of the PRKCZ promoter was analyzed using the UALCAN database. Furthermore, we investigated the mechanisms underlying PRKCZ inactivation in BC by treatment with transferase inhibitors, methylation-specific polymerase chain reaction (PCR) analysis, western blotting, and luciferase reporter gene assays. The degree of methylation and expression levels of PRKCZ, as regulated by DNA methyltransferase 1 (DNMT1), were quantified using quantitative PCR and western blotting. Results: Our analysis revealed that decreased expression of PRKCZ in BC was significantly correlated with poor clinical prognosis. Furthermore, we observed that hypermethylation of the PRKCZ promoter contributed to its reduced expression in BC. Notably, DNMT1 has been identified as a critical regulator of PRKCZ methylation. Conclusion Our findings elucidate the tumor-suppressive function of PRKCZ and provide insights into the molecular mechanisms underlying its downregulation in BC.

Objective To evaluate the clinical results of the Ilizarov technique for the treatment of the complex rigid talipes equinovarus deformities.Methods From July 2005 to July 2011,28 patients (41 feet) with rigid talipes equinovarus deformities which had been corrected with the Ilizarov technique were retrospectively analyzed,including 18 males (26 feet) and 10 females (15 feet) with an average age of 15.3 years.According to the classification system proposed by Diméglio,31 feet were categorized as grade Ⅲ,and 10 as grade Ⅳ.We performed corrections with a soft tissue release in 23 feet,and with a limited osteotomy in 18,and then a Ilizarov external fixator was applied.Anteroposterior and lateral X-rays were taken to compare the pre and postoperative data in terms of the angle of plantarflexion and dorsiflexion,the range of motion of the ankle joint,radiological measurements of the talocalcaneal angle.Results All the 28 patients achieved an outpatient follow-up,with an average of 25 months.All patients achieved a plantigrade foot with an almost normal appearance as the fixator was removed after applied for an average of 5.1 months (range,2-14).At the preoperative and final follow-up respectively,the angle of dorsiflexion of the foot was -45.0°±12.0° and 9.5°±5.5°,the angle of plantarflexion was 67.0°±14.0° and 45.5°±7.8°,talocalcaneal angle was 6.5°±4.5° and 22.5°±5.5° in anteroposterior radiograph and 5.5°±11.0° and 40.6°±8.5° in lateral radiograph.Spastic ischemia occurred in one foot and relieved by a slower distraction rate.Wire-hole infections occurred in 5 feet and treated by dressing changs,wire tract altering and antibiotic therapy,finally the infections were controlled.Deformity relapsed in one foot three months after the device was removed,then corrected with an additional fixator application and has not recurred till the final follow-up.Toe contracture and residual deformity occurred in 5 feet and 3 feet,respectively.Conclusion The Ilizarov technique is an effective method for correction of complex rigid talipes equinovarus deformities,with which the appearance and function of the foot could be kept as much as possible,and without impact on food development.