Background In recent years, the increasingly widespread application of nuclear and medical radiation technologies has resulted in a large number of occupational populations exposed to low-dose ionizing radiation (LDIR). At present, there is no consistent conclusion on the effects of long-term exposure to LDIR on the metabolic health of the occupational population. Objective To explore the association between long-term exposure to LDIR and metabolic syndrome (MetS) among medical radiologists. Methods A cross-sectional study was conducted to enroll 6431 medical radiologists who ordered occupational health checkups from January 2022 to December 2023, and basic information such as demographic characteristics, occupational characteristics, lifestyles, and dietary habits was collected through questionnaires. Physical examinations were conducted using a standardized protocol. Individual dose equivalents of occupational external exposure were monitored by dosimeters worn by medical radiologists. Logistic regression model was used for identifying influencing factors of MetS and sensitivity analysis, and restricted cubic spline model was used to explore the dose-response relationship between cumulative effective dose and MetS. Two-stage linear regression was used to evaluate threshold effect of association between cumulative effective dose and MetS. Results The positive rate of MetS was 13.6% (877/6431) among the enrolled 6431 study participants. The logistic regression showed that gender, age, monthly income, body mass index (BMI), cumulative effective dose, and smoking were influencing factors for MetS. The risk of MetS was higher in males (OR=1.511, 95%CI: 1.209, 1.888); using the < 30 years old group as reference, the risk of MetS was higher in the 30-39 years old (OR=1.509, 95%CI: 1.095, 2.079), 40-49 years old (OR=2.214, 95%CI: 1.551, 3.161), and ≥50 years old (OR=3.480, 95%CI: 2.338, 5.181) groups; using the <10000 yuan group as reference, the risk of MetS was lower in the group with a monthly income of 10000-14999 yuan (OR=0.715, 95%CI: 0.582, 0.878); the risk of MetS was higher in the BMI ≥ 24 kg·m⁻² group (OR=7.548, 95%CI: 6.223, 9.156); using the < 0.76 mSv group as reference, the risk of MetS was higher in the cumulative effective dose of 0.76-2.73 mSv group (OR=1.270, 95%CI: 1.017, 1.586); the risk of MetS was higher in the smoking group (OR=1.734, 95%CI: 1.428, 2.107). The results of restricted cubic spline showed that the cumulative effective dose was nonlinearly correlated with MetS (P _{non-linearity}=0.028), with an inflection point of 1.25 mSv. The risk of developing MetS increased by 34.1% for each unit increase in cumulative effective dose up to 1.25 mSv, whereas above 1.25 mSv, the statistical association was not significant. The sensitivity analysis results showed that after excluding the self-reported hypertensive and diabetic patients, the cumulative effective dose 0.76-2.73 mSv group still had an increased risk of developing MetS compared with the < 0.76 mSv group (P < 0.05), and the results were robust. Conclusion Among medical radiologists, male, age, BMI, and smoking are positively correlated with MetS, and monthly income is negatively correlated with MetS; cumulative effective dose is non-linearly correlated with MetS among medical radiologists.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Objective:The study retrospectively analyzed the etiology, clinical manifestations, emergency treatment and etiological treatment of a large sample of cases with hypercalcemic crisis.Methods:The clincial data of patients with hypercalcaemia cirisis who were administered in First Medical Center of Chinese PLA General Hospital from January 2009 to July 2022 were analyzed, inculding the general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, serological examination before and after treatment, pathological immunohistochemical findings and prognosis.Results:A total of 143 hypercalcaemia crisis patients(84 males and 59 females) with a mean age of 53.51±16.60 were enrolled. The most common disease was hyperparathyroidism(62/143), followed by solid malignancy(57/143) and multiple myeloma(12/143). Patients presented with digestive system symptoms at 76.91%, followed by neurological symptoms at 63.60%, urinary system symptoms at 58.76%, musculoskeletal symptoms at 55.23%, and cardiovascular system symptoms at 32.91%. After emergency calcium-lowering treatment, the remission rate of hypercalcemic crisis in 143 patients was 100%(143/143), and after etiological treatment, the remission rate of hypercalcemia was 85.31%(122/143).Conclusion:Early identification, emergency treatment and etiology treatment of hypercalcaemia crisis are essential. Effective treament with comprehensive calcium reduction can quickly relieve clinical symptoms and create opportunities for treatment for the cause. Targeted etiological interventions can lead to the correction or long-term remission of hypercalcemia.

Objective:To explore the predictors and reasons for restenosis in patients with Takayasu′s arteritis(TA) involved renal artery after plain old balloon angioplasty(POBA).Methods:The clinical data of 47 TA patients (47) with renal artery admitted to Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were analyzed, including 12 man and 35 female. The age ranged from 21 to 43 years old, with an average of (28.52±10.78) years old. All patient were diagnosed as TA and underwent POBA. The patients were divided into restenosis group ( n=18) and non-restenosis group ( n=29). The patients were followed up at 1, 3, and 6 months after surgery, and after 6 months, the patients were followed up every 6 months. All patients were followed up from 36 to 108 months.The basic clinical data of the two groups were compared, and the length of stent and residual stenosis were also compared. Measurement data were expressed as ( ± s), and t-test was used for comparison between groups. Counting data were expressed as the number of cases and percentage, and comparison between groups was analyzed using the chi-square test. Multivariate Logistic regression model was used to analyze the independent risk factors of restenosis after balloon dilation, and the OR value and 95% confidence interval were calculated. Logistic regression model was used to analyze the independent risk factors for restenosis after balloon dilation. Results:All patients received POBA and operation was successfully. Restenosis was found in 18 patients, and 29 patients remained normal during the follow-up. The primary patency rate was 61.7%. Multivariate Logistic regression analysis showed that HDL-C and lesion length were the influencing factors of restenosis after POBA in TA of renal artery. The serum HDL-C level was significantly lower and the lesion was significantly longer in restenosis group than in non-restenosis group ( P<0.05). The proportion of residual stenosis>20% was higher in restenosis group than in non-restenosis group ( P>0.05). Conclusion:Serum HDL-C level, lesion length may be may be independent influencing factors of restenosis after plain old balloon angioplasty in TA of the renal artery restenosis.

Objective To explore the diagnosis and treatment method of peripelvic cysts.Methods A retrospective analysis was conducted on 65 patients with peripelvic cysts admitted to the Department of Urology at Shanghai Xuhui Central Hospital from January 2019 to January 2023.The diagnostic value of ultrasound,intravenous urography(IVU),and computed tomography urography(CTU)for peripelvic cysts was compared,and the efficacy of different surgical treatments for peripelvic cysts was further evaluated.Results All 65 patients underwent ultrasound examination,which indicated cystic lesions at the renal hilum.55 patients underwent IVU examination,but no cyst enhancement was found.Among them,7 patients underwent retrograde pyelography due to poor imaging of the affected renal pelvis.All 53 patients who underwent CTU examination,which clearly showed the renal pelvis and cysts.Among the 65 patients,5 did not undergo surgical treatment and were followed up,while 60 underwent surgery.Four patients were considered for radical nephrectomy due to suspected malignancy.56 cases underwent renal cysts decompression surgery,including 11 open surgeries,37 laparoscopic surgeries,and 8 Da Vinci robot-assisted laparoscopic surgeries.The operative time in the open surgery group was significantly shorter than that in the laparoscopic surgery group and robot-assisted laparoscopic surgery group.Compared with the open surgery group and laparoscopic surgery group,the robot-assisted laparoscopic surgery group had less intraoperative blood loss,lower postoperative analgesic use,shorter time to first ambulation after surgery,and shorter hospital stay.Conclusions Ultrasound,IVU,and CTU are commonly used effective diagnostic tools for peripelvic cysts.Ultrasound can be used as a routine examination,while CTU is more accurate and has a higher diagnostic accuracy than IVU for this condition.Compared with open surgery,laparoscopic and robot-assisted laparoscopic cyst decompression surgery for peripelvic cysts result in less intraoperative blood loss and faster postoperative recovery.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Osteoarthritis(OA),characterized by cartilage degeneration,synovial inflammation,and subchondral bone remodeling,is among the most common musculoskeletal disorders globally in people over 60 years of age.The initiation and progression of OA involves the abnormal metabolism of chondrocytes as an important pathogenic process.Cartilage degeneration features mitochondrial dysfunction as one of the important causative factors of abnormal chondrocyte metabolism.Therefore,maintaining mitochondrial homeostasis is an important strategy to mitigate OA.Mitophagy is a vital process for autophagosomes to target,engulf,and remove damaged and dysfunctional mitochondria,thereby maintaining mitochondrial homeostasis.Cumulative studies have revealed a strong association between mitophagy and OA,suggesting that the regulation of mitophagy may be a novel therapeutic direction for OA.By reviewing the literature on mitophagy and OA published in recent years,this paper elaborates the potential mechanism of mitophagy regulating OA,thus providing a theoretical basis for studies related to mitophagy to develop new treatment options for OA.

The endoplasmic reticulum is a key site for protein production and quality control.More than one-third of proteins are synthesized and folded into the correct three-dimensional conformation in the endoplasmic reticulum.However,during protein folding,unfolded and/or misfolded proteins are prone to occur,which may lead to endoplasmic reticulum stress.Organisms can monitor the quality of the proteins produced by endoplasmic reticulum quality control(ERQC)and endoplasmic reticulum-associated degradation(ERAD),which maintain endoplasmic reticulum protein homeostasis by degrading abnormally folded proteins.The underlying mechanisms of protein folding and ERAD in mammals have not yet been fully explored.Therefore,this paper reviews the process and function of protein folding and ERAD in mammalian cells,in order to help clinicians better understand the mechanism of ERAD and to provide a scientific reference for the treatment of diseases caused by abnormal ERAD.