ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective:To explore the clinical characteristics, treatment and prognosis of splenic marginal zone lymphoma.Methods:The clinical data of 51 patients with splenic marginal zone lymphoma who underwent surgical treatment at Department of Hepatobiliary in Peking University People's Hosipital from Dec 2009 to Oct 2022 were retrospectively analyzed.Results:The patients 's average age was 60.5±11.8 years old, and the ratio of male to female rate was about 1:1. As of the last follow-up date of Feb 28, 2023, 8 patients died of the primary lymphoma and 14 patients suffered from disease progression. The 5-year progression free survival rate was 68%, and the overall survival rate was 79%. Univariate analysis showed that age ≥65 years old, decreased preoperative albumin, increased bilirubin level, and increased lactate dehydrogenase bode ill for overall survival time, but none of them were independent risk factors; Age ≥65 years old and diffuse large B cell transformation were independent risk factors.Conclusions:Surgery combined with comprehensive treatment which contained rituximab is currently the main treatment method. Splenectomy remains an important treatment and diagnostic method for patients with obvious symptoms or persistent unrelieved blood count abnormalities and unexplained splenomegaly. Advanced age, elevated bilirubin and lactate dehydrogenase, decreased albumin, and diffuse large B cell transformation, it may indicate poor prognosis.

Objective: To investigate the influencing factors of depressive symptoms among rural elderly patients with chronic diseases in China, so as to provide insights into depression prevention and control among the rural elderly patients with chronic diseases. Methods: The basic demographics, health status, and lifestyle of rural residents at ages of 65 years and older who had at least one chronic disease were retrieved from The Chinese Longitudinal Healthy Longevity Survey (CLHLS) database in 2018, and participants' depressive symptoms were assessed with The Center for Epidemiological Studies Depression-10 (CES-D-10) scale. Factors affecting the depressive symptoms were identified with a multivariable logistic regression model. Results: Totally 5 146 rural elderly patients with chronic diseases were enrolled, including 2 373 men (46.11%) and 2 773 women (53.89%). The prevalence of depressive symptoms was 27.13%. Multivariable logistic regression analysis identified having two and more children (OR=0.614, 95%CI: 0.387-0.975), living alone (OR=1.450, 95%CI: 1.192-1.764), life satisfaction (general, OR=1.933, 95%CI: 1.651-2.264; low, OR=5.366, 95%CI: 3.488-8.254), self-assessed health status (general, OR=2.697, 95%CI: 2.284-3.185; poor, OR=5.338, 95%CI: 4.262-6.685), disability in instrumental activities of daily living (OR=1.592, 95%CI: 1.328-1.908), sleep duration (normal, OR=0.502, 95%CI: 0.429-0.586; too long, OR=0.494, 95%CI: 0.405-0.603), exercise (OR=0.721, 95%CI: 0.607-0.856), watching TV (OR=0.787, 95%CI: 0.664-0.933), and gardening activities (OR=0.781, 95%CI: 0.626-0.975) as factors affecting depressive symptoms among rural elderly patients with chronic diseases. Conclusions The prevalence of depressive symptoms was 27.13% among rural elderly patients with chronic diseases. Number of children, living style, life satisfaction, health status, sleep duration, exercise, watching TV, and gardening activities are associated with the development of depressive symptoms among rural elderly patients with chronic diseases.

Abstract: Objective　To investigate the early diagnostic value of peripheral blood procalcitonin (PCT), C-reactive protein (CRP), fibrinogen (FIB) and D-dimer (D-D) levels in patients with pulmonary tuberculosis (PTB) complicated with bacterial pneumonia. Methods　A total of 102 patients who admitted to Department of Tuberculosis of Affiliated Nantong Hospital of Shanghai University from Jan 2021 to May 2022 were enrolled in this study and divided into a group (52 cases) with pulmonary tuberculosis (PTB) patients and a group (50 cases) with PTB patients complicated with bacterial pneumonia. The levels of PCT, CRP, FIB and D-D in the peripheral blood were measured, the differences and correlations in all indicators were compared among two groups. The sensitivity and specificity of these indicators in the early diagnosis of PTB complicated with bacterial pneumonia were analyzed by receiver operating characteristic (ROC) curve. Results　The levels of PCT, CRP, FIB and D-D in the peripheral blood from the PTB complicated with bacterial pneumonia group were 0.06 (0.04, 0.16) ng/mL, 38.00 (3.88, 96.10) mg/L, 4.51 (3.02, 6.07) g/L, and 0.59 (0.34, 1.88) mg/L, respectively, which were significantly higher than corresponding 0.04 (0.03, 0.04) ng/mL, 3.20 (0.84, 7.22) mg/L, 2.96 (2.48, 3.77) g/L, and 0.27 (0.17, 0.36) mg/L in the PTB group (Z=-4.784, -5.233, -3.853, -4.199, all P<0.001). Furthermore, the levels of CRP and FIB in the PTB complicated by bacterial pneumonia group were highly positively correlated (r=0.855, P<0.001). The area under the ROC curve (AUC) of PCT, CRP, FIB and D-D for early diagnosis of PTB complicated with bacterial pneumonia were 0.757, 0.794, 0.747 and 0.764, respectively. In addition, the AUC obtained by simultaneous measurement of PCT, CRP, FIB and D-D was as high as 0.916, and the sensitivity and specificity of diagnosing PTB complicated with bacterial pneumonia were increased to 85.7% and 96.9%, respectively, which were higher than those of individual indicators. Conclusions　Levels of peripheral blood PCT, CRP, FIB, and D-D all show varying degrees of increase in patients with PTB complicated with bacterial pneumonia, and detecting the levels of all four markers, rather than any single marker, can assist in early monitoring whether the tuberculosis patients are complicated with bacterial pneumonia.

Alzheimer' disease(AD)is a neurodegenerative disorder characterized by memory impairment and multiple cognitive deterioration.Acupuncture intervention in AD has potential efficacy,but the mechanism of onset is not clear.Blood oxygen level-dependent functional magnetic resonance imaging(BOLD-fMRI)has the unique advantages of accurately locating abnormal AD brain areas and monitoring and analyzing functional activities,providing technical support for the study of AD brain effects.It have found that abnormal changes in functional activity in response to brain regions and brain networks are closely related to the development of AD.Previous studies have shown that acupuncture can exert therapeutic effects by improving the functional impairment of multiple cognitive-related brain regions and brain networks in AD,which may be the mechanism of brain function in AD.Based on BOLD-fMRI technology,this paper elaborates on three aspects:commonly used data analysis methods of AD,the brain function mechanism of AD pathogenesis,and the brain effect study of acupuncture intervention in AD.In order to provide a reference for further exploring the brain effect of acupuncture intervention in AD.

Objective:To explore the clinical efficacy and adverse reactions of albumin-bound paclitaxel (Nab-P) and conventional paclitaxel combined with cisplatin and concurrent radiotherapy for the treatment of patients with locally advanced esophageal squamous cell carcinoma.Methods:Forty-nine patients with locally advanced esophageal squamous cell carcinoma admitted to the First People's Hospital of Suqian from November 2016 to May 2020 were included. Of the 49 patients, 23 cases were treated with Nab-P combined with cisplatin and concurrent radiotherapy (NP group), 26 cases were treated with conventional paclitaxel combined with cisplatin and concurrent radiotherapy (TP group). All patients received 2 cycles of chemotherapy. The curative efficacy was evaluated one month after the end of radiotherapy, and the curative effect and adverse reactions of the two treatment regimens were compared.Results:The objective remission rate in NP group was 78.3% (18/23), and the disease control rate was 100.0% (23/23). The objective response rate in TP group was 61.5% (16/26), and the disease control rate was 92.3% (24/26). The objective response rate and disease control rate in NP group were higher than those in TP group, but the differences were not statistically significant (both P > 0.05). The common adverse reactions were mainly hair loss, loss of appetite, bone marrow suppression, radiation esophagitis, radiation pneumonia, malaise and myalgia. The incidence rate of grade 3-4 acute bone marrow suppression in NP group (8.7%, 2/23) was lower than that in TP group (38.5%, 10/26), and the difference was statistically significant ( χ2 = 4.35, P = 0.037). The incidence rate of myalgia in NP group (26.1%, 6/23) was lower than that in TP group (61.5%, 16/26), and the difference was statistically significant ( χ2 = 4.85, P = 0.028). Conclusions:Nab-P combined with cisplatin and concurrent radiotherapy has good efficacy in the treatment of patients with locally advanced esophageal squamous cell carcinoma, and the incidence rate of adverse reactions is lower than that of conventional paclitaxel combined with cisplatin and concurrent radiotherapy, so that the regimen is safe.

Objective:To analyze the epidemiological and clinical characteristics of imported COVID-19 cases after SARS-CoV-2 vaccination and to provide evidence for the prevention and control of COVID-19.Methods:The imported COVID-19 cases in Chengdu as of April 15, 2021 were divided into the vaccinated group and unvaccinated group according to the history of SARS-CoV-2 vaccination. The epidemiological and clinical data of the cases were collected retrospectively, and the differences in epidemiological and clinical characteristics of the two groups were compared. Laboratory tests consisted of nucleic acid test, clinical index test, serum antibody test and lymphocyte test. Software WPS2019 was used for data management and software R 4.0.3 was used for statistical analysis.Results:A total of 75 COVID-19 cases were included in the analysis, in which 20 had received SARS-CoV-2 vaccination and only 4 with clinical symptoms, 55 patients did not receive SARS-CoV-2 vaccination, and 16 had clinical symptoms. In vaccinated group, the first injection time of vaccination ranged from July to November 2020, and 10 cases received two doses of vaccine simultaneously and 10 cases received two doses of vaccine at intervals of 14-57 days. The intervals between the completion of vaccination and the onset ranged from 87 days to 224 days. The differences in classification and clinical type between the two groups were significant. Significant differences were observed in case classification and clinical type between vaccinated group and unvaccinated group ( P<0.05). The vaccinated group had a relatively high proportion of asymptomatic infections (40.00%, 8/20), while mild infections were mainly observed in the unvaccinated group(76.36%,42/55). The differences in Ct values (ORF1ab gene and N gene) at the diagnosis were not significant between vaccinated group and unvaccinated group ( P>0.05), similar results were also observed in lymphocyte subtypes, procalcitonin and C-reactive protein level comparisons. Serum amyloid A level was higher in unvaccinated group than in vaccinated group ( P<0.05). However, the SARS-CoV-2 related serum antibody of IgM, IgG and total antibody levels were significantly higher in vaccinated group ( P<0.05). Conclusions:Risk of infection still exists with SARS-CoV-2 after vaccination, which can facilitate the production of specific serum antibody of IgM and IgG when people are exposed to the virus. It has a certain protective effect on SARS-CoV-2 infected persons. Vaccination can reduce the clinical symptoms and mitigate disease severity.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Objective To investigate the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in Chinese patients with ischemic stroke . Methods In this multi‐center study ,2 310 continuously inpatients with ischemic stroke diagnosed in 20 stroke screening and prevention project base hospitals from June 2015 to M ay 2016 were enrolled . Carotid ultrasonography and transcranial color‐coded sonography or transcranial Doppler were performed in all patients to confirm the presence of cerebral artery stenosis or occlusion . According to the distribution of lesions ,the subjects were divided into 2 groups :the simple intracranial artery stenosis group and the simple extracranial artery stenosis group . T he difference of risk factors between the two groups was compared . Results Of the 2 310 patients with ischemic stroke ,1 516 ( 65 .6% ) had simple intracranial artery stenosis and 794 ( 34 .4% ) had simple extracranial artery stenosis . T he incidence of anterior circulation artery stenosis was higher in the group of intracranial artery stenosis than that in the extracranial artery stenosis group ( 68 .1% vs 48 .7% , P ＜0 .001) . Posterior circulation artery stenosis and combined anterior with posterior circulation artery stenosis were more common in patients with extracranial artery stenosis group than those in intracranial artery stenosis group ( 36 .4% vs 22 .1% ,14 .9% vs 9 .8% ;all P ＜0 .001) . Univariate analysis of risk factors for stroke showed that patients with intracranial arterial stenosis had a higher prevelence of hypertension , diabetes ,obesity ,and family history of stroke ,and their systolic blood pressure ,diastolic blood pressure , body mass index ( BM I) ,fasting blood‐glucose ,glycosylated hemoglobin ,triacylglycerol ,total cholesterol , and low‐density lipoprotein cholesterol were significantly higher than those in the extracranial arterial stenosis group ( all P ＜ 0 .05 ) . T he proportion of elderly ( ≥ 65 years old ) ,male and smokers in the extracranial arterial stenosis group was significantly higher than that in the intracranial arterial stenosis group ( all P ＜0 .05) . Multivariate logistic regression analysis showed that elderly ( ≥65 years old) ,male , and smoking history were independent risk factors for extracranial arterial stenosis ( OR＝ 2 .012 ,1 .637 , 1 .325 ,respectively ;all P ＜0 .05) . While hypertension ,diabetes ,less physical activity ,and high BM I levels were independent risk factors for simple intracranial arterial disease ( OR ＝ 1 .301 ,1 .252 ,1 .248 ,1 .030 , respectively ;all P ＜0 .05) . Conclusions There are significant differences in the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in patients with ischemic stroke in China .

N-methyladenosine (mA), a ubiquitous RNA modification, is installed by METTL3-METTL14 complex. The structure of the heterodimeric complex between the methyltransferase domains (MTDs) of METTL3 and METTL14 has been previously determined. However, the MTDs alone possess no enzymatic activity. Here we present the solution structure for the zinc finger domain (ZFD) of METTL3, the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14. We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3' consensus sequence, but does not to one without. The ZFD thus serves as the target recognition domain, a structural feature previously shown for DNA methyltransferases, and cooperates with the MTDs of METTL3-METTL14 for catalysis. However, the interaction between the ZFD and the specific RNA is extremely weak, with the binding affinity at several hundred micromolar under physiological conditions. The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel β-sheet. Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface. As a division of labor, the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues from β-sheet and zinc finger 2. Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded, which may permit the cooperation between the two domains during catalysis. Together, the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA mA modification.