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.

Hepatocellular carcinoma (HCC) poses a significant hazard to public health in China because of its high incidence, high mortality, and high rate of advanced stages. Early detection and treatment of HCC by screening for high-risk populations is instrumental for enhancing survival rates among patients with HCC in China. Liver resection, local ablation, interventional therapy, radiotherapy, and drug therapy are all effective treatments for patients with HCC, and appropriate treatments can be selected based on different tumor stages. However, the condition of patients with HCC in China is complicated, and no single specialty offers the complete spectrum of care. The disease-centered multidisciplinary team for HCC is a crucial method to prolong the survival of patients with HCC and optimize their quality of life. Recent advancements in different disciplines have brought new opportunities in HCC treatments and altered multidisciplinary management approaches. Meanwhile, new challenges have emerged, and many problems have yet to be addressed.

Background Electroplating technology is widely used in the mechanical manufacturing industry. Electroplating workers may be exposed to occupational hazards such as chromium, zinc, cyanides, and sulfuric acid. With the continuous improvement of protective conditions, occupational hazards have been effectively controlled, but there is less focus on the potential acute occupational poisoning that may occur during the electroplating process. Objective To identify causes of an acute chromium poisoning accident occurred during the cleaning process of electroplating tank in a hardware processing plant, and to formulate relevant prevention and control measures to avoid similar poisoning accidents. Methods Occupational history, medical history, and treatment process of the poisoned worker were inquired in detail, his inpatient medical records were consulted , and his blood samples were tested. Occupational health investigation and testing were carried out at the scene of the poisoning accident. Results The air concentration of peak exposure (CPE) and permissible concentration-time weighted average (CTWA) of chromium and its compounds in the workplace were 0.49 mg·m⁻³ and 0.31 mg·m⁻³ respectively. The results of auxiliary test were Serum chromium 4175.85 μg·L⁻¹, serum creatinine 1370.2 μmol·L⁻¹, urea 42.28 mmol·L⁻¹, and urine osmotic pressure 248 mosm·L⁻¹. The final diagnosis was occupational acute severe toxic nephropathy (chromium and its compounds) and occupational chemical skin moderate burn (chromic acid, sulfuric acid). The prescribed treatment included right lower limb expansion skin grafting, hemodialysis and symptomatic support. The patient’s condition was stable and gradually improved after the treatment. Conclusion The main causes of the poisoning accident include weak awareness of the employer of occupational disease prevention and control; failures in fulfilling legal obligations of occupational disease prevention and control, implementing effective occupational disease prevention measures, and providing proper occupational health and safety training and effective personal protective equipment. In order to protect the health of workers, the relevant government departments and employers should attach great importance to the prevention and control of occupational diseases, such as strengthening training and education, increasing the intensity of occupational health supervision, and urging employers to implement occupational disease prevention measures in accordance with the law.

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 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 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.

The application of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) can be limited due to a lack of compatible protospacer adjacent motif (PAM) sequences in the DNA regions of interest. Recently, SpRY, a variant of Streptococcus pyogenes Cas9 (SpCas9), was reported, which nearly completely fulfils the PAM requirement. Meanwhile, PAMs for SpRY have not been well addressed. In our previous study, we developed the PAM Definition by Observable Sequence Excision (PAM-DOSE) and green fluorescent protein (GFP)‍-reporter systems to study PAMs in human cells. Herein, we endeavored to identify the PAMs of SpRY with these two methods. The results indicated that 5'-NRN-3', 5'-NTA-3', and 5'-NCK-3' could be considered as canonical PAMs. 5'-NCA-3' and 5'-NTK-3' may serve as non-priority PAMs. At the same time, PAM of 5'-NYC-3' is not recommended for human cells. These findings provide further insights into the application of SpRY for human genome editing.
CRISPR-Associated Protein 9/metabolism* ; CRISPR-Cas Systems ; DNA ; Gene Editing/methods* ; Humans ; Streptococcus pyogenes/metabolism*

Objective:To explore the safety and efficacy of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating painful chronic pancreatitis patients with pancreatic stones.Methods:The painful chronic pancreatitis patients receiving P-ESWL alone or P-ESWL combined with ERCP at Shanghai Pudong New Area Gongli Hospital from August 2019 to December 2021 were retrospectively analyzed. The success rate of stone fragmentation following P-ESWL, occurrence of postoperative complications, stone clearance rate of the main pancreatic duct and degree of pain relief in the follow-up were evaluated.Results:Among 113 patients, 7 patients were treated with P-ESWL alone and 106 patients were treated by P-ESWL combined with ERCP. The success rate of stone fragmentation was 98.2%. The occurrence of P-ESWL complications was 6.2%. Complete clearance of the main pancreatic duct stones was achieved in 75.2% of patients. With the mean follow-up of 17.5(3-31) months, complete pain relief was achieved in 84.1% of patients. The pain frequency and VAS score of patients treated with P-ESWL alone and P-ESWL combined with ERCP were obviously lower than those before treatment, and the body weight and body mass index were significantly higher than those before treatment, all with statistically significant differences (all P value <0.01). Conclusions:P-ESWL is safe and effective for the management of painful chronic pancreatitis patients with main pancreatic duct stones.