[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People's Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events. Results: A total of 81.82% (n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546-1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% (n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients (n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion: Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

[Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias].

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

Social sleepers: The effects of social status on sleep in terrestrial mammals.

Social status among group-living mammals can impact access to resources, such as water, food, social support, and mating opportunities, and this differential access to resources can have fitness consequences. Here, we propose that an animal's social status impacts their access to sleep opportunities, as social status may predict when an animal sleeps, where they sleep, who they sleep with, and how well they sleep. Our review of terrestrial mammals examines how sleep architecture and intensity may be impacted by (1) sleeping conditions and (2) the social experience during wakefulness. Sleeping positions vary in thermoregulatory properties, protection from predators, and exposure to parasites. Thus, if dominant individuals have priority of access to sleeping positions, they may benefit from higher quality sleeping conditions and, in turn, better sleep. With respect to waking experiences, we discuss the impacts of stress on sleep, as it has been established that specific social statuses can be characterized by stress-related physiological profiles. While much research has focused on how dominance hierarchies impact access to resources like food and mating opportunities, differential access to sleep opportunities among mammals has been largely ignored despite its potential fitness consequences.

[Value of ATP synthase C subunit in predicting cardiac function and outcomes of sepsis].

Objective: To investigate the value of serum mitochondrial ATP synthase C subunit level in the evaluation of cardiac functional status and prognosis in patients with sepsis. Methods: A total of 165 sepsis patients admitted to the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Wenzhou Medical University from January 1, 2017 to December 31, 2018 were included, there were 103 males (62.4%) and 62 females (37.6%) with an age of (63±14) years. Human ATP synthase lipid binding protein (ATP5G1) ELISA kit was used to detect the level of serum ATP synthase C subunit within 24 h after admission to EICU, and compared with that in 45 healthy subjects. Clinical data of patients were collected and divided into groups according to different left ventricular ejection fraction (LVEF) and clinical outcomes. The differences in clinical indicators among each group were compared to evaluate the value of serum ATP synthase C subunit level in the evaluation of cardiac functional state and prognosis of patients with sepsis, and the independent risk factors for cardiac functional state and prognosis of patients with sepsis were analyzed. Results: Compared with the control group, the level of serum ATP synthase C subunit in the sepsis group was higher ((116±62) µg/L vs (77±34) µg/L, P<0.001). Compared with normal cardiac function group, the level of serum ATP synthase C subunit in septic cardiac dysfunction group was higher (P<0.001). Compared with the survival group, the level of serum ATP synthase C subunit in the death group was higher (P<0.05). The receiver operating curve (ROC) was drawn to analyze the value of ATP synthase C subunit, creatine kinase isoenzyme (CK-MB), B-type natriuretic peptide (BNP), troponin I (cTnI), left atrial end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic volume, left ventricular end systolic volume in evaluating the cardiac function in patients with sepsis, and the area under the curve (AUC) was 0.928, 0.661, 0.837, 0.814, 0.703, 0.831, 0.794 and 0.765, respectively. The cut-off value, sensitivity and specificity of ATP synthase C subunit in it was 139.44 ng/L, 100% and 75.2%, respectively. ROC was drawn to analyze the prognostic value of age, urea nitrogen (BUN), ATP synthase C subunit, APACHEⅡ score and SAPSⅡ score in patients with sepsis, and the AUC was 0.719, 0.772, 0.656, 0.868 and 0.884, respectively. The cut-off value, sensitivity and specificity of ATP synthase C subunit in it was 131.24 ng/L, 61.9% and 68.7%, respectively. Logistic regression analysis showed that age, BUN, ATP synthase C subunit, cardiac dysfunction, APACHEⅡ score and SAPS Ⅱ score were independent risk factors for the prognosis of patients with sepsis. Conclusion: The level of serum ATP synthase C subunit is closely related to cardiac dysfunction in patients with sepsis, and can effectively predict the prognosis of patients with sepsis.

Integrated transcriptomics and metabolites at different growth stages reveals the regulation mechanism of bolting and flowering of Angelica sinensis.

The root of Angelica sinensis is one of the most widely used traditional Chinese medicines. In commercial planting, early bolting and flowering (EBF) of ca. 40% of 2-year-old plants reduces root yield and quality. Although changes in physiology in bolted plants have been investigated, the mechanism activating EBF has not been identified. Here, transcriptomics profiles at four different growth stages (S1 to S4) were performed, gene expression was validated by qRT-PCR and the accumulation of endogenous hormones quantified by HPLC. A total of 60,282 unigenes were generated, with 2,282, 1,359 and 2,246 differentially expressed genes (DEGs) observed at S2 versus S1, S3 versus S2 and S4 versus S3, respectively; 558 genes that co-exist in at least three stages from S1 to S4 were obtained. Functional annotation classified 38 DEGs linked to flowering pathways: photoperiodism, hormone signalling, carbohydrate metabolism and floral development. The levels of gene expression, hormones (GA1 , GA4 and IAA) and soluble sugars were consistent with the EBF. It can be concluded that the EBF of A. sinensis is controlled by multiple genes. This integrated analysis of transcriptomics, together with targeted hormones and soluble sugars, provides new insights into the regulation of EBF of A. sinensis.

Effect of UV-B radiation on growth, flavonoid and podophyllotoxin accumulation, and related gene expression in Sinopodophyllum hexandrum.

Sinopodophyllum hexandrum is an alpine medicinal plant that produces the anticancer compound podophyllotoxin (PPT). Although a positive relationship between PPT content and altitude has been proved and low temperature enhances plant growth and PPT accumulation has also been revealed, the role of UV radiation in regulating growth and PPT accumulation is still unclear In this study, morphophysiological traits, metabolites content and related genes expression were investigated by exposing S. hexandrum seedlings to treatment with UV-B radiation. The results showed that the contents of soluble sugars and flavonoids, and the expression levels of genes involved in glycometabolism (XET and ß-1,3-glucanase) and flavonoid biosynthesis (PAL,C4H,4CL,CHS1 and DTX41) were enhanced in response to UV-B compared to CK. Moreover, genes involved in stress tolerance (MYB, WRKY,APX3 and EX2) were also upregulated in response to UV-B radiation. Although the whole plant biomass exhibited slightly increased values that depended largely on root development, the contents of chlorophyll and PPT and the expression levels of genes involved in photosynthesis (matK, ndhF,rbcL and ycf5) and PPT biosynthesis (C3H,CCoAMT,CCR,CAD, DPO, PLR,SDH, CPY719A23,OMT3,CYP71CU1,OMT1and 2-ODD) were significantly decreased in response to UV-B compared to CK. It can be concluded that UV-B radiation promotes soluble sugars and flavonoids accumulation, but inhibits PPT biosynthesis in S. hexandrum.

[Design and clinical application of specialized protective cap for patients with alopecia after autologous hair transplantation].

Objective: To investigate the design of specialized protective cap for patients with alopecia after autologous hair transplantation and its application value in nursing care after autologous hair transplantation. Methods: The author designed a kind of specialized protective cap for patients with alopecia after autologous hair transplantation with elastic gauze, fiber, silica gel, and other materials. It was divided into two parts, the front piece was mainly used to protect the hair receiving site, and the back piece was mainly used for pressure hemostasis at the hair donor site. From February 2017 to January 2019, 81 patients with alopecia and had autologous hair transplantation in the First Affiliated Hospital of Air Force Military Medical University, who met the inclusion criteria, were enrolled in this prospective controlled study. According to the tail number of admission number of each patient, 43 patients with odd numbers were recruited in protective cap group (38 males and 5 females, aged 23 to 52 years) and 38 patients with even numbers were recruited in convention group (34 males and 4 females, aged 22 to 55 years). After hair transplantation surgery, patients in the two groups received routine postoperative education. Patients in the conventional group were treated with conventional dressing after surgery. On this basis, patients in protective cap group wore the specialized protective caps for at least 1 week continuously except for necessary dressing change, wound clean, and dressing remove. The follow-ups was performed by responsible doctors and nurses at clinic. The postoperative hemorrhage at the hair donor site on post surgery day (PSD) 3 and swelling of scalp at the surgical site on PSD 7, the folliculitis at the hair receiving site and survival condition of transplanted hair follicle at the receiving site, and satisfaction score within 3 months after surgery were observed and recorded. Data were statistically analyzed with two independent sample t test, chi-square test, and Fisher's exact probability test. Results: (1) On PSD 3, one patient in protective cap group had hemorrhage at the hair donor site, which was significantly less than 8 patients in convention group (P<0.05). (2) On PSD 7, 4 patients in protective cap group had swelling of scalp at the surgical site, which was significantly less than 11 patients in convention group (χ(2)=5.160, P<0.05). (3) Within 3 months after surgery, 0 patient in protective cap group had folliculitis at the hair receiving site, which was less than 3 patients in convention group. (4) In 3 months after surgery, the survival number of hair follicle in each 100 transplanted hair follicles at the hair receiving site of patients in protective cap group was 94.9±2.8, which was significantly more than 91.1±4.7 in convention group (t=4.354, P<0.01). (5) The patients' satisfaction score in protective cap group was (14.2±2.6) points, which was significantly higher than (12.1±3.0) points in convention group (t=3.338, P<0.01). Conclusions: After autologous hair transplantation, the specialized protective cap can reduce postoperative hemorrhage at the hair donor site, swelling of scalp at the surgical site, as well as improve the survival rate of transplanted hair follicles at the hair receiving site and score of patient satisfaction.

[Baicalin regulates STIM1-mediated calcium overload and reduces apoptosis of cardiomyocytes induced by lipopolysaccharide].

Objective: To investigate the protective effect of Baicalin on apoptosis induced by lipopolysaccharide in H9C2 cardiomyocytes and its possible mechanism. Methods: In order to establish apoptosis model of H9C2 cardiomyocytes, H9C2 cardiomyocytes were cultured and divided into four groups: the control group; the baicalin group was treated with baicalin at the final concentration of 10µmol/L for 12 hours; the LPS group was stimulated with LPS at the final concentration of 1 µg/ml for 6 hours; The LPS+baicalin group was stimulated with LPS at the final concentration of 1 µg/ml for 6 hours within treated with baicalin at the final concentration of 10µmol/L for 12 hours. Collecting cell samples, CCK-8 (The Cell Counting Kit-8) was used to detect cell activity, and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) was used to detect the expression levels of apoptosis. Laser Scanning Confocal Microscopy was used to detect the expression levels of store-operated calcium entry in H9C2 cardiomyocytes. Western blot was used to detect the protein expression levels of STIM1, cleaved-caspase3, Bax and Bcl-2. Fluorogenic quantitative PCR was used to detect the mRNA expression level of STIM1. Results: Compared with the control group, LPS-induced H9C2 cardiomyocyte survival rate decreased (P<0.05), the expression level of apoptosis increased (P<0.05), the internal flow of calcium increased (P<0.05), the expression levels of cleaved-caspase3, Bax protein levels increased (P<0.05), Bcl-2 protein level decreased (P<0.05), the expression of STIM1 mRNA and protein level increased (P<0.05). Compared with LPS group, the survival rate of H9C2 cardiomyocytes in baicalin intervention group increased (P<0.05), the expression level of apoptosis decreased (P<0.05), the internal flow of calcium decreased (P<0.05), the expression levels of cleaved-caspase3, Bax protein decreased (P<0.05), and the level of Bcl-2 protein increased (P<0.05), the expression of STIM1 mRNA and protein level decreased (P<0.05). Conclusion: Baicalin may alleviate LPS-induced cardiomyocyte apoptosis by alleviating calcium overload, and improve cell survival.

[Clinical analysis of 22 cases of syndrome caused by acute poisoning].

Objective: To analyze the clinical characteristics, treatment and prognosis of rhabdomyolysis (RM) caused by acute poisoning.Summarize the clinical characteristics and treatment experience, pay attention to the complications and improve the quality of rescue. Methods: We collecte and summarize the clinical data, treatment and prognosis of 22 cases of RM caused by acute poisoning. Results: We found that 21 patients (95.5%) had muscle damage, 13(59.1%) with coma, 8(36.4%) with brown, tea or even soy sauce urine, 6(27.3%) had acute renal injury (AKI), and 4(18.2%) had multiple organ dysfunction syndrome (MODS). After the treatment, 21 cases (95.5%) got better, and one case were discharged. All the patients with AKI were survived, three of them were treated by hemodialysis, and the other recovered gradually after massive fluid replacement. Conclusion: Acute poisoning combined with RM is not uncommon in clinic. We should pay attention to examination of serum enzymes and other indicators, observe the clinical symptoms and make early diagnosis. The key to diagnosis and treatment is early fluid resuscitation, comprehensive treatment, blood purification and maintain the stability of water and electrolyte.

Altered exosomal miR-181d and miR-30a related to the pathogenesis of CVB3 induced myocarditis by targeting SOCS3.

OBJECTIVE: MicroRNAs are a group of gene expression regulators and some of which have been confirmed to be associated with acute viral myocarditis (VM). This study aims to find new biomarkers for VM diagnosis and explore the roles of miRNAs during the pathogenesis of VM. PATIENTS AND METHODS: 23 patients with acute myocarditis and 12 controls were included in this research. The expression of 10 candidate miRNAs in the serum exosome was examined by qRT-PCR. The direct targets were predicted using bioinformatics tools and then confirmed by dual luciferase assay and immunoblotting. Levels IL-6 of cell culture supernatants were determined by enzyme-linked immunosorbent assay. Six weeks old male mice were injected intraperitoneally with Coxsackievirus B3 (CVB3) and then treated by miRNA inhibitors through tail vein injection. RESULTS: Five miRNAs were found to have disturbed expression in the exosome and may have the potential to be used as biomarker for VM diagnosis. Meanwhile, the expression of miR-30a and -181d was also altered in the cells after CVB3 infection. We identified SOCS3 as a direct target of miR-30a and -181d. Furthermore, during CVB3 infection, up-regulated miR-30a and -181d are related to enhanced IL-6 level via modulating SOCS3 expression. miRNA inhibitors injection increased mice survival rate after CVB3 infection. CONCLUSIONS: miR-30a and -181d contribute to the over-activated inflammatory response to viral infection of the heart during coxsackievirus infection.

[Comparison of different scoring systems in prognosis evaluation of acute poisoning].

Objective: To compare the predictive value of PSS, APACHEII, SAPSII and SOFA in the prognosis evaluation of acute poisoning. Methods: Clinical data (including PSS score, APACHEII score, SAPSII score and SOFA score, within 24 hours after admission) of 231 acute poisoning patients admitted to the emergency intensive care unit EICU of our hospital from January 2015 to October 2016 was retrospectively analyzed. The patients were divided into the survival group and the dead group according to the 28-day clinical outcomes, comparing the differences of clinical data in each group. To analyze the correlation between PSS score, APACHEII score, SAPSII score and SOFA score in each group, comparing the value and the area under the ROC curve of four scoring systems and evaluate the predictive value of the four scoring systems. Results: Comparing with the survival group and the dead group, PSS score, APACHEII score, SAPSII score and SOFA score were significantly different (P<0.01) . PSS score, APACHEII score, SAPSII score and SOFA score were significantly positive correlation (P<0.01) , the area under the ROC curve (AUC) of the four scoring systems were 0.833, 0.887, 0.843 and 0.843 respectively. The area under the ROC curve (AUC) of APACHEII score was higher than PSS score, SAPSII score and SOFA score, the difference was statistically significant (z=2.351, 2.317, 2.217; P=0.019, 0.021, 0.027) , there was no significant difference in the area (AUC) between the three scoring curves (P>0.05) . The cutoff value (cut-off) , sensitivity, specificity and accuracy rates of PSS score, APACHEII score, SAPSII score and SOFA score were (2.5, 93.1%, 50.9%, 61.5%) , (14.5, 82.8%, 75.7%, 77.48%) , (31.5, 77.6%, 76.90%, 77.08%) , (5.5, 77.60%, 74.60%, 75.35%) . Conclusion: PSS score, APACHEII score, SAPSII score and SOFA score can evaluate the prognosis of patients with acute poisoning, but the APACHEII score is better than the other three scoring systems in evaluating the prognosis for its evaluation ability and accuracy rate.

Genital HPV infection among heterosexual and homosexual male attendees of sexually transmitted diseases clinic in Beijing, China.

Human papillomavirus (HPV) has been identified as etiologic agent of various cancers for both men and women. However, HPV vaccine has not been recommended for men in China by far. To provide more evidences to promote HPV vaccination among males at high-risk of infection, this study investigated genital HPV genotypes among male attendees of sexually transmitted disease (STD) clinic. Male attendees (⩾18 years old) were recruited from STD clinic of Beijing Ditan Hospital. Data on sociodemographic characteristics and self-reported sexual behaviors were collected based on questionnaire. Genital swab specimens were collected for HPV genotypes. Finally, a total of 198 eligible participants were included in the study. Nearly half of them were infected with at least one type of HPV. The prevalence of genital infection among participants with only heterosexual behaviors (50·91%, 56/110) was significantly higher than those with only homosexual behaviors (36·36%, 32/88) (P < 0·001). However, the distribution pattern of the most frequently observed HPV subtypes were found to be similar between these two subgroups. HPV31, HPV18, HPV16 and HPV58 were the most frequently identified high-risk types and HPV11, HPV6, HPV81 and HPV61 were the most frequently observed low-risk types. Our results, although need further verification by larger sample size, suggested that currently available HPV vaccines covered most prevalent HPV types observed in Chinese men. As HPV vaccine has been approved for application in females in China, molecular epidemiological studies and intervention studies among high-risk males should be promoted as well.

[Analyses on relevant factors of the prognosis of elderly patients with acute poisoning].

Objective: To explore the risk factors influencing the prognosis of elderly patients with acute poisoning. Methods: We retrospected 177 elderly patients with Acute Poisoning who were treated in the emergency department of the first affiliated hospital of wenzhou medical university from July 2009 to May 2015. According to the outcome of patients, we distributed the patients to death group (31 cases) and survival group (146 cases) , compared the clinic data and using multivariate analysis with Logistic regression to prognosis factors. Results: There were 177 cases in total, with 146 survivors (82.5%) and 31 deaths (17.5%) . In which 102 cases (57.6%) had chronic underlying diseases. There were 28 cases of pesticide poisoning in the death group, and the fatality rate of pesticide poisoning was 23.5%. The mortality rate was 12.8% in the 60-69 years-old group (11/86) , 20% (13/65) in the 70-79 years-old group, 26.9% (7/26) in the 80-89 years-old group. The most common reason of poisoning was intentional ingestion, with 100 cases (56.5%) . The tract of the poisoning was mainly in digestive system, including 148 cases (83.6%) . The PSS score and APACHE-II score were 2.97±0.18 and 19.8±2.8 in the death group, 2.27±0.81 and 12.8±5.3 in the survival group. Compared with the survival group, poison (pesticides or non) 、poisoning route、cause of poisoning、PSS score、APACHEⅡ score have significant difference in death group (P<0.05) . Poison (pesticides or non) 、PSS score、APACHEⅡ, were the independent risk factors of poor prognosis. Conclusion: Most of the elderly patients with acute poisoning have one or more chronic underlying diseases, the digestive tract ingestion and pesticide poisoning are more common. The fatality rate of the old patients is significantly higher than that of non elderly poisoning. Type of toxications, PSS score and APACHE-II score are the prognostic factors in elderly patients.

[The function of NLRP1 in noninfectious pulmonary injury following allogeneic hematopoietic stem cell transplantation].

Objective: To explore the function of NLRP1 in noninfectious pulmonary injury (nonIPI) after allogeneic stem cell transplantation (allo-HSCT) . Methods: In this study, we established the model of allo-HSCT with C57BL/6 and NLRP(-/-) mouse as recipients. Chimera rate was measured by flow cytometry. The HE staining was used to observe the pathology changes in the lungs. NLRP1 and relevant inflammatory proteins were measured by Western Blot. Results: On the day 14 after allo-HSCT, the chimera rate was more than 96%, HSCs of donors had been successfully transplanted into recipients. HE staining showed that nonIPI occurred after allo-HSCT. The degrees of injuries reached the peak on day 21. In addition, the expressions of MPO, NLRP1, p20, Mature-IL-1ß and Mature-IL-18 had same tends with the degrees of nonIPI. When we knocked out NLRP1 gene of recipients, the degrees of nonIPI reduced and the expressions of MPO, p20, Mature-IL-1ß and Mature-IL-18 were less than in non-knockout group. Conclusion: allo-HSCT could cause nonIPI and high expressions of MPO, p20, IL-1ß, IL-18, NLRP1. Knocking out NLRP1 gene could alleviate the degrees of nonIPI and reduce the expressions of relevant inflammatory proteins, indicating that NLRP1 might be one of factors contributed to nonIPI after allo-HSCT.