Objective To investigate the feasibility of granzyme B(GB)promoter-controlled ferritin heavy chain(FTH1)reporter gene expression for monitoring the activation status of chimeric antigen receptor T cells(CAR-T)by magnetic resonance imaging(MRI).Methods Cytotoxic T lymphocytes(CTLs)were screened by Ficoll density gradient centrifugation and flow sorting.The GB promoter and FTH1 gene were ligated together with disialoganglioside 2(GD2)CAR,and lentiviral vectors were transfected into CTLs to construct GD2-CAR-T/pGB-FTH1 cells.GD2-CAR-T/pCMV-FTH1,GD2-CAR-T,and T cells served as control cells.CytoTox96@non-radioactive cytotoxicity was used to detect the killing effect of each group of cells after co-culture with human neuroblastoma cells(SK-N-SH).ELISA was employed to detect the coincubation factor as well as the amount of GB secretion.Western blotting,Prussian blue staining and cellular MRI were applied to detect the expression of the FTH1 gene after co-culture.Results CTLs were successfully obtained,and then GD2-CAR-T/pGB-FTH1,GD2-CAR-T/pCMV-FTH1 and GD2-CAR-T cells were constructed.The killing effect,co-incubation factor and GB secretion of the above 3 groups of cells were significantly higher than those of the T cells,and the level of GB expression was highest at day 1,and then decreased in order at day 3 and day 7 after co-culturing with SK-N-SH cells.The relative expression of FTH1 and iron content of the GD2-CAR-T/pGB-FTH1 cells showed the same trend as GB expression,and the MRI signals were gradually increased.There were no significant differences in the relative expression of FTH1,iron content and MRI signals in the GD2-CAR-T/pCMV-FTH1 cells at all time points.No FTH1 expression or iron aggregation was observed in the GD2-CAR-T and T cells groups.Conclusion MRI based on the FTH1 reporter gene driven by the granzyme B promoter can reflect the GB expression level and tumor killing effect of CAR-T cells,which provides a potential real-time visual means to monitor the cell activation status for CAR-T therapy.

Objective:To explore the risk factors of all-cause death in hypertensive patients in the community.Methods:A cohort of 4 049 hypertensive patients who participated in annual health checkups at Xinzhuang Community Health Service Centre of Shanghai Minhang district from January to December 2012 were enrolled in the study. All-cause death was the endpoint event of this study, and patients were divided into a fatal group and a survival group. The collection date for the endpoint event was December 2022. A multivariate Cox regression model was used to analyse the independent risk factors of all-cause mortality among hypertensive patients in the community.Results:Among 4 049 patients aged (67.9±7.1) years, 1 856 (45.8%) were males. There were 610 cases in the fatal group and 3 439 cases in the survival group. Multivariate Cox proportional regression showed that male gender ( HR=1.446, 95% CI: 1.200-1.742, P<0.001), older age ( HR=1.130, 95% CI: 1.118-1.143, P<0.001), higher waist-to-height ratio ( HR=8.117, 95% CI: 2.235-29.481, P=0.001), positive urinary protein ( HR=2.974, 95% CI: 2.202-4.016, P<0.001), high fasting blood glucose ( HR=1.070, 95% CI: 1.012-1.131, P=0.017), and history of stroke ( HR=1.819, 95% CI: 1.414-2.340, P<0.001) were independent risk factors for all-cause mortality in hypertensive patients, while exercise≥1/week ( HR=0.816, 95% CI: 0.668-0.996, P=0.046) and taking lipid-lowering medications ( HR=0.459, 95% CI: 0.223-0.947, P=0.035) were protective factors for all-cause mortality. Conclusion:For hypertensive patients, male gender, older age, higher waist-to-height ratio, positive urinary protein, high fasting blood glucose, and history of stroke are risk factors for all-cause mortality, while exercise≥1/week and taking lipid-lowering medications are protective factors.

Objective:To analyze the association between sleep status and ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.Methods:It was a cross sentional study. Hypertensive patients who underwent 24-hour ambulatory blood pressure monitoring from May 2021 to April 2023 in Shanghai Xinzhuang Town were enrolled. The demographic information and sleep status of patients were obtained from the questionnaire. A TM-2430 blood pressure monitor was used to measure 24-hour ambulatory blood pressure, and the relevant indicators, including blood pressure level and blood pressure coefficient of variation were documented. The association between sleep status and blood pressure indicators was analyzed with multivariate linear regression model.Results:A total 1 135 patients aged (65.07±12.61) years were enrolled, and 473 (41.67%) of whom were males. The sleep time was<7 hours in 76 cases, 7- 8 hours in 219 cases and >8 hours in 840 cases; the bedtime was earlier than 22∶00 in 415 cases, between 22∶00 and 23∶00 in 474 cases and later than 23∶00 in 246 cases; the wake-up time was before 6∶00 in 230 cases, between 6∶00 and 7∶00 in 521 cases and after 7∶00 in 384 cases. Multivariate linear regression analysis showed that after controlling for gender and age, the sleep time was negatively associated with diurnal, noctumal and 24-hour diastolic blood pressure levels (all P<0.05), and positively associated with diurnal and noctumal systolic blood pressure coefficient of variation, noctumal diastolic blood pressure coefficient of variation, and 24-hour systolic blood pressure coefficient of variation (all P<0.05).The bedtime was positively associated with diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), diastolic blood pressure (all P<0.05); and negatively associated with diurnal systolic blood pressure coefficient of variation, diurnal diastolic blood pressure coefficient of variation, noctumal systolic blood pressure coefficient of variation, 24-hour systolic blood pressure coefficient of variation, and 24-hour diastolic blood pressure coefficient of variation (all P<0.05). The wake-up time was positively associated with diurnal systolic blood pressure, diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), and positively associated with diurmal systolic blood pressure and diastolic blood pressure (both P<0.05). Conclusion:Sleep status is closely associated with ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba

Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.
Humans ; Mice ; Animals ; Cell Line, Tumor ; Nitric Oxide Donors/pharmacology* ; Sesquiterpenes/pharmacology* ; Leukemia/drug therapy* ; Biological Assay ; Cell Proliferation

Objective:To investigate the complicated virus infection of infants with pertussis and its effect on the disease.Methods:From January 2019 to March 2020, a total of 100 hospitalized infants with pertussis were admitted to the Second Affiliated Hospital of Medical College of Shantou University, nasopharyngeal swabs were collected for detection of ten pathogens including pertussis, namely respiratory syncytial virus(RSV), parainfluenza virus(PIV), bordetella pertussis (BP), human rhinovirus(HRV), human bocavirus(HBoV), human metapneumovirus(hMPV), influenza B virus (INF-B), adenovirus, influenza A virus and cytomegalovirus(CMV). According to the results of pathogen detection, all infants were divided into single detection group of BP(single detection group) and co-detection group of BP combined with viruses(co-detection group). The clinical data of the two groups were retrospectively analyzed and compared to explore the differences of clinical characteristics and its impact on the course of disease.Results:Among 100 cases, there were 54(54.0%) boys and 46(46.0%)girls.The age ranged from 28 days to 2 years and 5 months, with a median age of 3.5 months.Fifty-six cases were classified as single detection group, while 44 cases were included into co-detection group.Among infants in co-detection group, fourteen cases were co-infected with CMV(31.8%, 14/44), seven cases with HRV(15.9%, 7/44), seven cases with PIV(15.9%, 7/44), four cases with RSV(9.1%, 4/44), one case with hMPV(2.2%, 1/44), eight cases with CMV+ HRV(18.2%, 8/44), one case with HRV+ HBoV (2.2%, 1/44), one case with CMV+ PIV(2.2%, 1/44)and one case with CMV+ PIV+ INF-B(2.2%, 1/44). The number of infants in the single detection group who had cyanosis before treatment, requiring repiratory support, PICU admission, severe pneumonia or abnormal myocardial enzymes were higher than those in the co-detection group( P<0.05), while the months of age were lower than that in the co-detection group( P<0.05). When comparing the clinical characteristics of infants over three months of age, only the number of cases of combined cyanosis before treatment and the number of days in hospital were higher in the single detection group than those in the co-detection group ( P<0.05), no statistically significant differences were found in the other clinical characteristics between the two groups( P>0.05). Conclusion:The cases of infants requiring repiratory support, complicated with severe pneumonia or abnormal myocardial enzymes in the single detection group are higher than those in the co-detection group, which may be attributed to the small age of months.

Objective:To analyze the detection rate of respiratory syncytial virus(RSV)and human rhinovirus(HRV), in different months and age groups, and the clinical characteristics in children in eastern Guangdong from 2019 to 2020.Methods:Pharyngeal swabs were collected from 6 658 children with respiratory tract infections hospitalized in the Second Affiliated Hospital of Shantou University Medical College from January 2019 to December 2020, and respiratory pathogen nucleic acid was detected.The detection rate, month distribution, age group distribution, and clinical characteristics of single RSV as well as single HRV positive cases were analyzed and compared.Results:There were 416 single RSV positive cases(6.25%)and 341 single HRV positive cases(5.12%).The detection rates of RSV was higher than those of HRV, and the difference was statistically significant( χ2=7.880, P<0.05).The detection rates of HRV in March, April, November and December were higher than those of RSV, and the detection rates of RSV in July, August and September were higher than those of HRV, with statistically significant difference( P<0.05).The highest detection rate of RSV was in the age group of ≤6 months with a detection rate of 13.47%(192/1 425), which gradually decreased with age, and the difference was statistically significant( P<0.01).The detection rates of HRV fluctuated between 4.21% and 6.13% in each age group, and the differences among the detection rates of each age group were not statistically significant( P>0.05).All RSV-positive cases showed cough, while 77.13%(263/341)of HRV-positive cases showed cough, with a statistically significant difference( P<0.001).The incidence of wheezing in RSV-positive cases was 37.26%(155/416)compared with 28.45%(97/341)in HRV-positive cases, with a higher incidence of wheezing in RSV than that in HRV, and the difference was statistically significant( P<0.05).In terms of indicators to assess severe pneumonia, RSV-positive cases showed a higher proportion of increased respiratory rate, decreased oxygen saturation or dyspnea than HRV-positive cases, and all differences were statistically significant( P<0.05). Conclusion:The detection rate of single RSV is higher than that of single HRV in children with respiratory infections in eastern Guangdong from 2019 to 2020.The epidemic season of RSV is mainly in autumn, and the epidemic season of HRV is mainly in winter and spring.RSV is more susceptible up to 6 months of age, and the detection rate decreases gradually with age, and there is no significant difference in the detection rate of HRV by age.RSV-positive cases are more likely to have cough and wheeze.RSV-positive cases are more likely to have increased respiratory rate, decreased oxygen saturation, or respiratory distress.

Objective:To investigate the clinical features of adenoviral encephalitis (AE), and to provide reference for clinical diagnosis and treatment of adenoviral encephalitis.Methods:From January 2012 to December 2020, 1 185 cerebrospinal fluid (CSF) samples of hospitalized children with suspected central nervous system infection in the Second Affiliated Hospital of Shantou University Medical College were collected for the detection of 22 common respiratory pathogens and common pathogens for encephalitis by polymerase chain reaction. Records of patients with adenovirus positive in CSF were reviewed and relevant clinical manifestations, laboratory tests and imaging examination results were collected for analysis.Results:Among 1 185 CSF samples, 242 samples were positive for viral nucleic acid, with detection rate of 20.4%, including 1.9%(23/1 185) of adenovirus. As for 23 children diagnosed with AE, 18 were male, five were female, with the age of (44.8±35.9) months, ranging from two months and 19 days to 10 years. Of 23 children, 21(91.3%) presented with fever, followed by convulsions (16 cases, 69.6%), headache (four cases, 17.4%), vomiting (11 cases, 47.8%), consciousness change (11 cases, 47.8%) and emotion disturbance (three cases, 13.0%). Among 23 children, eight cases had white blood cell counts (WBC) of (6 to <10)×10 9/L, 10 cases had WBC of (10 to 20)×10 9/L and the white blood cell classification was mainly neutrophils (21 cases, 91.3%), and C reactive protein of 20 cases (87.0%) was in the normal range. Cerebrospinal fluid examination showed that WBC were less than 15×10 6/L in 20 cases (87.0%), and WBC ≥15×10 6/L in three cases, which were up to 500×10 6/L; the protein of 19 cases was in the normal range, the glucose of 15 cases was in the normal range, and the chloride of 19 cases was in the normal range. Among 16 cases with brain magnetic resonance imaging examination, eight cases did not show abnormality, six cases with local meningeal linear enhancement, one case with small intracranial malacia, and one case with extensive intracranial lesions. For 13 cases who received electroencephalogram (EEG) test, seven cases showed normal EEG or marginal state, four cases showed extensive medium and high amplitude slow wave, one case showed spike wave or spike slow wave and one case had both of the above two changes. Among 23 children, 22 cases recovered including one case had secondary epilepsy, and the remaining one case had severe brain dysfunction and was unable to suck when discharged, with an indwelling gastric tube and accompanied by secondary epilepsy. Conclusions:The clinical manifestations and auxiliary examinations of children with AE have no obvious specificity. Most children with AE have a good prognosis, but a small number of them may have serious sequelae.

Objective:To retrospectively analyze the clinical effects and complications of alcohol inactivation, irradiation inactivation, and liquid nitrogen inactivation in the treatment of femur osteosarcoma in children, in an attempt to provide a theoretical basis for clinical selection of in vitro inactivation methods of tumor bone segment. Methods:The clinical data of 93 children with femur osteosarcoma admitted to the Department of Bone and Soft Tissue, the Affi-liate Cancer Hospital of Zhengzhou University from January 2008 to December 2017 were retrospectively analyzed, and 40 children, including 21 males and 19 females, aged 8-18 (13.65±2.87) years, who were treated with in vitro inactivation and replantation of autogenous tumor bone segment, were screened.Among these children, there was alcohol inactivation in 15 cases, irradiation inactivation in 12 cases, and liquid nitrogen inactivation in 13 cases.A comparison was drawn on these 3 inactivation methods with respect to bone healing time, bone healing rate, tumor recurrence rate, infection rate, fracture or fixation failure rate, and revision rate. Results:All those 40 children were subject to valid medical followed-up, with the alcohol inactivation group for (102.60±16.55) months, the irradiation inactivation group for (59.33±6.39) months, and the liquid nitrogen inactivation for (36.85±6.49) months.The difference in follow-up time of 3 groups was statistically significant ( P<0.05). Compared with other 2 groups, the index of bone healing time, bone healing rate, infection rate and revision rate in the alcohol inactivation group were unfavorable, which showed a significant difference (all P<0.05); However, there was no significant difference in the recurrence rate, fracture rate or fixation failure rate compared with other 2 groups (all P>0.05); There was no significant difference in all above indexes between the irradiation group and the liquid nitrogen group (all P>0.05). Conclusions:Three in vitro inactivation methods for the treatment of tumor bone segment are safe and reliable.The alcohol inactivated bone has a long healing time and more complications.Both irradiation inactivation and liquid nitrogen inactivation are clinical options, but irradiation inactivation requires professional equipment, which may limit the clinical application.

We report a case of maternal asymptomatic COVID-19 in a patient with typical CT image of pneumonia in the third trimester, and both the mother and baby were well. The patient, a 30-year-old female, was transferred to Yichun People's Hospital at 37 +3 gestational weeks because of a positive 2019 novel coronavirus nucleic acid result over seven hours. Her husband and mother-in-law were diagnosed with COVID-19 eight days before her admission and on the same day, respectively. The patient reported no discomfort before admission, and there were no abnormalities in the prenatal course during her pregnancy. On February 13 (the second day of admission), a patchy blurred shadow was observed in the lower lobe of the right lung in chest CT scan, and a live baby girl was delivered by a precaution-based emergent cesarean section because of suspected fetal distress shown in electrical fetal heart monitoring. Both the mother and the newborn were isolated separately after the operation without etiological examination of amniotic fluid, umbilical cord blood, placenta, etc. All the medical staff involved in the cesarean section were isolated as well. The mother was healthy and remained asymptomatic after delivery, while antiviral and anti-inflammatory treatment was offered. COVID-19 nucleic acid tests of pharyngeal swab were negative on the 4 th and 6 th day after operation. Chest CT on the 5 th day after delivery showed inflammation in the lower lobe of the right lung, and reexamination on the 8 th day showed a slight absorption of the inflammation. Samples of peripheral blood and pharynx swab were obtained from the newborn on the day of birth and four and seven days after birth and novel coronavirus nucleic acid test were all negative. The mother and baby dyad were discharged nine days after operation. And novel coronavirus nucleic acid tests were all negative in all medical staff involved.