With the extensive application of uranium in military, industrial and civil fields, the possibility of human exposure to uranium has become increasingly likely. When uranium is accidentally released into the environment, it can enter the human body by various pathways and accumulate in the kidneys, leading to proximal tubule epithelial cell damage or even death, and in severe cases, nephrotoxicity. Uranium exerts both chemical and radiological toxicity, with its kidney-damaging effects primarily attributed to chemical toxicity. Low-level uranium exposure causes mild kidney damage, while prolonged or high-level exposure alters kidney structure and biomarker level of uranium-induced nephrotoxicity (such as creatinine, urea nitrogen and kidney injury molecule-1, etc.). Uranium exposure also induces DNA damage and mutations, kidney inflammation, and renal cell autophagy. Current research on uranium nephrotoxicity primarily focuses on uranium-induced mitochondrial dysfunction, which leads to oxidative stress and apoptosis (mainly by mitochondrial and endoplasmic reticulum pathway), ultimately causing renal tissue damage. However, the molecular mechanisms underlying uranium-induced kidney toxicity remain incomplete. Future research on mechanism of uranium-induced cell damage, especially metabolism, intracellular distribution, and additional mechanisms, remains a long-term and challenging endeavor.

Coronavirus infection can cause serious respiratory and digestive system diseases in hu-mans and animals.In recent years,the frequent outbreaks and newly outbreaks of coronavirus in-fection have threatened global public health and the development of livestock and poultry.Howev-er,the development of anti-coronavirus drugs and vaccines was restricted due to the insufficient understanding of the mechanisms of coronavirus pathogenesis and cross species transmission.Re-verse genetic manipulation technology is a powerful tool in virological research,which can be used for the study of pathogenesis mechanisms,replication mechanisms and function analysis of protein.It is also be used in the development of attenuated or gene labeled vaccines,and antiviral drugs.Due to the large genome and complex structure of the coronavirus,the reverse genetic manipulation technology of coronavirus has been lagging for a long time.With the continuous updating of molec-ular biology methods,various new construction strategies have emerged.This article focuses on the construction strategy of the reverse genetic operating system for coronavirus,as well as its applica-tion in virus transmission and pathogenic mechanisms,and development of vaccines,which will provide favorable tools for the prevention and control of the coronavirus infection.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Objective:To explore the prevalence rate of restless leg syndrome (RLS) and its related influencing factors in patients with maintenance hemodialysis (MHD) in Anhui province.Methods:It was a cross-sectional study, including regular MHD patients in blood purification centers of 27 hospitals in southern, central and northern Anhui province from January to March 2020. The investigation included general demographic characteristics, primary diseases, complications, dialysis-related conditions and drug use. According to the presence or absence of RLS, the patients were divided into RLS group and non-RLS group, and the differences of clinical data between the two groups were compared. Logistic regression analysis method was used to analyze the influencing factors of RLS.Results:The study included 3 025 MHD patients, aged (54.8±12.8) years old, with 1 819 males (60.1%) and 1 206 females (39.9%). The dialysis age was (5.5±3.8) years. The prevalence rates of RLS in MHD patients were 8.8% (265/3 025), of which 13.7% (77/561), 7.7% (88/1 145) and 7.6% (100/1 319) in southern, central and northern Anhui province, respectively. The prevalence rates of RLS in MHD patients in secondary and tertiary hospitals were 9.5% (55/577) and 8.6% (210/2 448), respectively. Proportion of hypertension, dialysis age, intact parathyroid hormone, alkaline phosphatase, 25(OH)D3, and proportions of secondary hyperparathyroidism, erythropoietin use, iron supplements, active vitamin D use, calcimimetic use, dialysis blood flow <250 ml/min and low-flux dialyzers in RLS group were higher than those in non-RLS group, while hemoglobin level and proportions of non-calcium-phosphorus binders and high-flux dialyzers were lower than those in non-RLS group (all P<0.05). Multivariate logistic regression analysis results showed that long dialysis age ( OR=1.188, 95% CI 1.031-1.369, P=0.017) and high alkaline phosphatase ( OR=1.007, 95% CI 1.001-1.013, P=0.047) were correlated with a higher risk of RLS in MHD patients. Conclusions:The prevalence rate of RLS in MHD patients in Anhui province is 8.8%. The prevalence rates of RLS in MHD patients in southern, central and northern Anhui province are 13.7%, 7.7% and 7.6%, respectively. The prevalence rate of RLS in secondary and tertiary hospitals are 9.5% and 8.6%, respectively. Long dialysis age and high alkaline phosphatase are associated with a high risk of RLS in MHD patients.

Objective To analyze the micronucleus levels of peripheral blood lymphocytes of medical radiation workers, and to provide a basis for radiation protection to reduce occupational hazards caused by ionizing radiation. Methods A total of 1072 medical radiation workers were selected into radiation group, and 329 healthy adults who underwent pre-employment occupational physical examination and intended to be radiation workers were selected into control group. The micronucleated lymphocyte frequency was determined by whole blood micro-culture. Results There were no significant differences in micronucleated cell frequency and micronucleus frequency between the radiation group and the control group (both P > 0.05). The detection rate of micronucleus abnormalities in the radiation group was significantly higher than that in the control group (P < 0.001). Female radiation workers had significantly higher micronucleated cell frequency, micronucleus frequency, and the detection rate of micronucleus abnormalities than male radiation workers (all P < 0.001). Between different types of work, significant differences were observed in micronucleated cell frequency and micronucleus frequency (both P < 0.05), but not in the detection rate of micronucleus abnormalities (P > 0.05). Radiation workers with different lengths of working showed significant differences in micronucleated cell frequency (P < 0.05), micronucleus frequency (P < 0.05), and the detection rate of micronucleus abnormalities (P < 0.001). Significant differences were observed in micronucleated cell frequency and micronucleus frequency between different age groups (both P < 0.05). The Spearman’s rank correlation analysis showed that micronucleated cell frequency and micronucleus frequency were positively correlated with the age of radiation workers (both P < 0.001). Conclusion The micronucleus frequency of radiation workers was related to the type and length of work, and had a positive correlation with age. Radiation protection should be enhanced for workers engaged in medical radiation for a long period, especially female workers and workers with a long length of service.

Objective:To explore the cancer incidence and mortality in registration areas of Shanxi Province in 2014.Methods:The data of 12 cancer registration areas of Shanxi Province in 2014 were taken to analyze the characteristics of cancer incidence and mortality for patients with different age and gender in different areas. And then the results were compared with the malignant cancer incidence and mortality in the nationwide.Results:There were 11 703 new cases, including 6 559 males and 5 144 females in registration areas of Shanxi Province in 2014, and the incidence rate was 221.21/10 5, while the age-standardized incidence rate of Chinese population and world population was 163.91/10 5 and 163.25/10 5, respectively. The cancer incidence rate in urban areas was 247.02/10 5 and the age-standardized incidence rate of Chinese population was 171.35/10 5. In rural areas, the cancer incidence rate was 205.98/10 5 and the age-standardized incidence rate of Chinese population was 159.03/10 5. The common cancer sites were stomach, lung, esophagus, liver and colorectum for males. And breast, cervix, lung, esophagus, stomach were the common cancer sites for females. There were 7 283 malignant death cases, including 4 548 males and 2 735 females. The crude cancer mortality rate was 137.66/10 5, and the age-standardized mortality rate of Chinese population was 99.67/10 5 and world population was 100.11/10 5. The crude cancer mortality rate in urban areas was 141.03/10 5 and the age-standardized incidence rate of Chinese population was 92.84/10 5. In rural areas, the crude cancer mortality rate was 135.68/10 5 and the age-standardized mortality rate of Chinese population was 103.69/10 5. Male common malignant tumor deaths included lung cancer, gastric cancer, liver cancer, esophageal cancer and colorectal cancer, while lung, stomach, liver, esophagus and cervix were the common cancer death sites for females. Conclusions:The incidence and mortality of malignant tumors in registration areas in Shanxi Province are mainly lung cancer, upper gastrointestinal cancer and cervix uteri cancer. The incidence rates of stomach cancer and cervical cancer are high.

Objective: To analyze the frequency and composition of risk-related cytogenetic abnormalities (CAs) in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The frequency and composition of risk-related CAs from a cohort of 1 015 Chinese patients with NDMM were determined by interphase fluorescence in situ hybridization (iFISH) , individually or in combination. Results: Of the cohort of 1 015 Chinese patients with NDMM, the frequencies of IgH arrangement, del (13q) /13q14, 1q gain and del (17p) were 54.0%, 46.4%, 46.1% (35.8% and 12. 7% for 3 or more than 3 copies) and 9.9%, respectively. Among 454 patients who had the baseline information for all risk-related CAs [except t (14;20) , which was not covered by the FISH panels performed routinely at all five centers], the frequencies of t (4;14) , t (11;14) or t (14;20) were 14.1%, 11.2% and 4.8%, respectively; of them, 44.3% patients carried 2 or more CAs (28.0%, 13.4% and 2.9% for 2, 3 or ≥4 CAs) ; 83.3%, 95.0% or 68.6% patients with 1q gain, del (17p) or IgH rearrangement had 1 or more additional CA (s) , with del (13q) /13q14 as the most frequently accompanied CA; 57.7% patients carried at least 1 HRCA; the incidences of double-hit (DH) MM (DHMM) (=2 HRCAs) and triple-hit (TH) (THMM) (≥3 HRCAs) were 14.3% and 2.9%, respectively. Conclusions Our results provided an up-to-date profile of CAs in Chinese NDMM patients, which revealed that approximately 58% patients might carry at least 1 HRCA, and 17% could experience so-called DHMM or THMM who presumably had the worst outcome.

BACKGROUND: Lung cancer is one of the most deadly cancers in the world for human. In recent years, the effect of targeted therapy has become increasingly significant. Apatinib is a multi-target anti-tumor drug that is currently under study. The purpose of this study is to investigate the effects of Apatinib on the biological characteristics of lung cancer cells and its possible mechanism. METHODS: Lung cancer cell lines H1299 and H3255 were cultured in vitro. The effects of Apatinib on proliferation, migration and invasion of H1299 and H3255 cells were detected by cell proliferation assays wound healing assays and Transwell assays. The protein expression related to cancer angiogenesis and invasion was detected by Western blot. RESULTS: Apatinib significantly inhibited the proliferation, migration and invasion of H1299 and H3255 in a concentration-dependent manner. Western blot showed that with the increasing of drug concentration, VEGF, VEGFR2, N-cadherin, MMP9, MMP2 and Vimentin were down-regulated, and E-cadherin were up-regulated. CONCLUSIONS Apatinib can inhibit the invasion and migration of lung adenocarcinoma cells H1299 and H3255. By regulation of epithelial-mesenchymal transition and the expression of matrix metalloproteinase-related proteins.
Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Humans ; Lung Neoplasms ; pathology ; Neoplasm Invasiveness ; Pyridines ; pharmacology

BACKGROUND: Lung cancer is one of the common malignant tumors that impair human health. With the development of epigenetics, the researchers found that enhancer of Zeste homolog 2 (EZH2) is highly expressed in lung cancer tissue and its expression is closely related to the prognosis. EZH2 inhibitor can also enhance the sensitivity of tumor cells to a variety of anti-tumor drugs. The purpose of this study is to investigate the effect of combination of EZH2 inhibitor and gefitinib on the proliferation, apoptosis and migration of Gefitinib-resistant lung cancer cells. METHODS: PC9 and PC9/AB2 cells were used for this study. CCK-8 and EdU experiment were used to detect combined treatment on cell viability and proliferation activity; Wound healing assay and Transwell chamber experiment were used to determine the effects of combination therapy on cell migration ability; Flow cytometry was used to detect the effect of combination therapy on EZH2 and apoptosis; Western blot was used to observe the effect of combination therapy on epidermal growth factor receptor (EGFR) signaling pathway-related proteins expression. RESULTS: In gefitinib-resistant cell line PC9/AB2, gefitinib combined with EZH2 inhibitor GSK343 can significantly inhibit cell viability, reduce cell migration and increase cell apoptosis. At the same time, combination therapy can significantly inhibit the expression of EZH2 and phosphorylation EGFR proteins. CONCLUSIONS The combination of EZH2 inhibitor GSK343 and gefitinib sensitize PC9/AB2 cell to gefitinib response. This study also suggests that synergistic therapy plays a role in the reversal of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) resistance in lung cancer.
Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drug Synergism ; Enhancer of Zeste Homolog 2 Protein ; antagonists & inhibitors ; ErbB Receptors ; antagonists & inhibitors ; Gefitinib ; pharmacology ; Humans ; Lung Neoplasms ; pathology ; Protein Kinase Inhibitors ; pharmacology