Low-dose targeted radionuclide therapy synergizes with CAR T cells and enhances tumor response.

Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering ß-emitting 177Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response. To determine the optimal dosage and timing of 177Lu-DOTATATE treatment, we measured CAR T cell infiltration and expansion in tumors longitudinally through positron emission tomography (PET) using a SSTR2-specific positron-emitting radiotracer,18F-NOTA-Octreotide. In animals receiving CAR T cells and a low-dose (2.5 Gy) of TRT following the administration of 177Lu-DOTATATE, we observed a rapid regression of large subcutaneous tumors, which coincided with a dramatic increase in serum proinflammatory cytokines. Tumor burden was also reduced when a higher radiation dose (6 Gy) was delivered to the tumor. However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.

[A cross-sectional survey and influencing factors analysis of knowledge, attitude, and behavior of enteral nutrition implemented by nurses in burn intensive care unit].

Objective: To investigate the status of knowledge, attitude, and behavior of enteral nutrition implemented by nurses in burn intensive care unit (BICU) and analyze its influencing factors. Methods: A multi-center cross-sectional survey research method was used. On May 8th, 2022, 107 BICU nurses who met the inclusion criteria were selected from the burn departments of the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Guangdong Provincial People's Hospital, the First Affiliated Hospital of Guangxi Medical University, the Affiliated Hospital of Qinghai University, the Second Affiliated Hospital of Air Force Medical University, the Affiliated Hospital of Nantong University, Guiyang Steel Factory Staff Hospital, and the Second Affiliated Hospital of Kunming Medical University. The self-made nurses' enteral nutrition nursing knowledge-attitude-behavior questionnaire for severely burned patients was used to investigate the nurses' gender, age, working years, professional title, position, highest educational background, and whether they received systematic training in knowledge of enteral nutrition, the scores of each factor, and the total scores of knowledge, attitude, and behavior dimensions of enteral nutrition in nurses. The nurses were classified according to the general data, and the total scores of their knowledge, attitude, and behavior of enteral nutrition were calculated. Data were statistically analyzed with independent sample t test, one-way analysis of variance, Mann-Whitney U test, and Kruskal-Wallis H test. According to the results of univariate analysis and combined with clinical experience and significance, the generalized linear model analysis was carried out to screen the independent influencing factors of the total scores of knowledge, attitude, and behavior of enteral nutrition in BICU nurses. Results: A total of 107 nurses were surveyed, and 107 valid questionnaires were collected, with an effective recovery rate of 100%. In the BICU nurses' enteral nutrition knowledge-attitude-behavior questionnaire, the total scores of knowledge, attitude, and behavior were 44±13, 87±15, and 70±19, respectively. Most of the BICU nurses in this survey were female, aged 22-48 (31±6) years, and the number of nurses worked for 1-5, 6-10, and ≥11 years was evenly distributed. The majority of the professional titles of nurses were nurses, positions were responsible nurses, and the highest educational background was undergraduate. Forty-four nurses received systematic training in knowledge of enteral nutrition. There were statistically significant differences in the total scores of knowledge of enteral nutrition among BICU nurses with different ages, working years, professional titles, positions, highest educational background, and whether they received systematic training in knowledge of enteral nutrition (with H values of 27.36, 15.27, and 10.19, respectively, Z values of -3.33, -2.59, and -6.46, respectively, P<0.05). There were no statistically significant differences in the total scores of attitude and behavior of enteral nutrition among BICU nurses with different gender, ages, working years, professional titles, positions, highest educational background, and whether they received systematic training in knowledge of enteral nutrition (P>0.05). Age (26-30, 31-35, and ≥36 years old), highest educational background (undergraduate), and the systematic training received in enteral nutrition knowledge were the independent influencing factors for the total score of knowledge of enteral nutrition in BICU nurses (with 95% confidence intervals of 0.12-0.36, 0-0.30, 0.03-0.31, 0.01-0.32, and 0.19-0.40, respectively, standardized regression coefficients of 0.24, 0.15, 0.17, 0.17, and 0.29, respectively, P<0.05). There were no independent influencing factors for the total scores of enteral nutrition attitude and behavior of BICU nurses in different characteristics (P>0.05). Conclusions: The BICU nurses have low cognitive level in the implementation of enteral nutrition, their concept needs to be updated in time, and their behavior needs to be further standardized. Age (26-30, 31-35, and ≥36 years old), highest educational background (undergraduate), and the systematic training received in enteral nutrition knowledge were the independent influencing factors for the knowledge of enteral nutrition in BICU nurses.

[Hemophagocytic syndrome secondary to COVID-19: a case report and literature review].

Objective: To improve the awareness of hemophagocytic syndrome(HPS) secondary to COVID-19 (COVID-sHPS). Methods: We reported an adult case of COVID-sHPS, including clinical presentation, laboratory examinations, histopathological findings, treatment strategy, and outcome. We also conducted literature research in PubMed database and Wanfang database using the keywords "COVID-19" and "hemophagocytic syndrome" and subsequently summarized relevant literature. Results: A 49-year-old man was admitted to our hospital after 4 weeks of recurrent fever. Prior to this hospitalization, he had received an empiric combination therapy with antibiotics and antiviral drugs against SARS-CoV-2. His vital signs were within the normal range and no abnormalities were found on physical examination on admission. After admission, throat swab nucleic acid tests were weakly positive for SARS-CoV-2, and negative for influenza and respiratory syncytial virus. Blood nucleic acid tests for cytomegalovirus and EB virus were negative, as was blood mNGS. Laboratory tests showed a series of abnormalities, including leukopenia, thrombocytopenia, low fibrinogen, elevated serum ferritin, elevated transaminase, decreased NK cell activity, and hemophagocytosis in bone marrow. According to the HPS-2004 diagnostic criteria, he was diagnosed with hemophagocytic syndrome, which was high likely to be caused by COVID-19 infection due to the lack of evidence of genetic risk factors and other clear triggers. He was initially treated with dexamethasone at a dose of 10 mg·m-2·d-1 and his condition improved rapidly. The literature search identified twenty-three articles on COVID-sHPS, 22 of which were in English. A total of 89 patients had COVID-sHPS and 55 (61.7%) were male. COVID-sHPS could occur at any age, but mainly in adults (86/89, 96%). Fever was reported in the literature with a clear description of the course of the disease. Most HPS occurred during the acute phase of COVID-19, but 3 patients developed HPS during the convalescent phase. Almost all reported cases presented with increased ferritin, elevated transaminases, elevated triglycerides, and cytopenia, mainly anemia and thrombocytopenia. In the retrieved literature, HS-score≥169 was frequently used to diagnose COVID-sHPS, and glucocorticoid in combination with immunoglobulin was the most common treatment strategy. COVID-sHPS had a poor prognosis and a high mortality rate (84.2%, 75/89). Conclusions: The prognosis of COVID-sHPS is poor, so clinicians should raise their awareness of the disease, identify high-risk suspected populations, and arrange reasonable relevant examinations for definite diagnosis and early initial treatment to improve their outcome.

Evaluation of renal function in chronic kidney disease (CKD) by mDIXON-Quant and Amide Proton Transfer weighted (APTw) imaging.

BACKGROUND: Chronic kidney disease (CKD) is a long-term condition that affects >10% of the adult population worldwide. Noninvasive assessment of renal function has important clinical significance for disease diagnosis and prognosis evaluation. OBJECTIVE: To explore the value of mDIXON-Quant combined with amide proton transfer weighted (APTw) imaging for accessing renal function in chronic kidney disease (CKD). MATERIALS AND METHODS: Twenty-two healthy volunteers (HVs) and 30 CKD patients were included in this study, and the CKD patients were divided into the mild CKD (mCKD) group (14 cases) and moderate-to-severe CKD (msCKD) group (16 cases) according to glomerular filtration rate (eGFR). The cortex APT (cAPT), medulla APT (mAPT), cortex R2⁎ (cR2⁎), medulla R2⁎ (mR2⁎), cortex FF (cFF) and medulla FF (mFF) values of the right renal were independently measured by two radiologists. Intra-group correlation coefficient (ICC) test was used to test the inter-observer consistency. The analysis of variance (ANOVA) was used to compare the difference among three groups. Mann-Whitney U test was used to analyze the differences of R2⁎, FF and APT values among the patient and HV groups. Area under the receiver operating characteristic (ROC) curve (AUC) was used to analyze the diagnostic efficiency. The corresponding threshold, sensitivity, and specificity were obtained according to the maximum approximate index. The combined diagnostic efficacy of R2⁎, FF, and APT values was analyzed by binary Logistic regression, and the AUC of combined diagnosis was compared with the AUC of the single parameter by the Delong test. RESULTS: The cAPT value of the HV, mCKD and msCKD groups increased gradually. The mAPT value and cR2⁎ values of the mCKD and msCKD groups were higher than those of the HV group, while the mFF value of the mCKD group was lower than HV group (all P < 0.05). The cAPT and mAPT values showed good diagnostic efficacy in evaluating different degrees of renal damage, while cR2⁎ and mFF values showed moderate diagnostic efficacy. When combining the APT, R2⁎, and FF values, the diagnostic efficiency was significantly improved. CONCLUSION: mDIXON-Quant combined APTw imaging can be used for improved diagnosis of CKD.

[Clinical characteristics of sudden sensorineural hearing loss with acute cerebral infarction].

Objective: To analyze the clinical and imaging features of patients with sudden sensorineural deafness and acute cerebral infarction in order to provide evidence for early recognition of such diseases. Methods: This was a case series reporting study. A retrospective analysis was performed on the clinical and imaging data of 29 patients with sudden hearing loss (SHL) who admitted to the Otolaryngology Head and Neck Surgery Department of Beijing Tiantan Hospital from January 2017 to December 2021 and diagnosed with acute cerebral infarction using MRI-DWI. Results: The patients were aged 31-71 years, with an average age of 56±12 years, and 82.8% (24/29) were men. In total, 82.8% (24/29) of the patients had three or more atherosclerotic risk factors, and 24.1% (7/29) had a history of SHL. The hearing types were flat and total deafness: 86.2% (25/29) of the patients had severe hearing loss, 27.6% (8/29) had bilateral SHL, 17.2% (5/29) had further hearing loss during hospitalization, and 82.8% (24/29) had dizziness or vertigo at the onset. The signs of central nervous system involvement mainly included speech impairment, diplopia, dysphagia, central facial paralysis, facial and limb hypoesthesia, ataxia, and decreased muscle strength. Imaging evaluation showed that 21 cases were located in the posterior circulation supply area and 8 cases in the anterior circulation supply area. Additionally, 82.8% (24/29) patients had vertebrobasilar artery stenosis, and 58.6% (17/29) patients had severe vertebrobasilar artery stenosis or occlusion. Conclusions: Patients with SHL who progress to cerebral infarction often have multiple atherosclerotic risk factors and SHL. Most of the patients are middle-aged and older men who often complain of dizziness or dizziness accompanied by severe flat and total deafness with unilateral or bilateral SHL. Imaging findings suggest that most patients have posterior circulation infarction, often accompanied by severe stenosis or occlusion of the vertebrobasilar artery.

[A comparative analysis of the clinical symptoms of benign paroxysmal positional vertigo between older and young and middle-aged patients].

Objective: To compare the differences in clinical symptoms and the time required for diagnosis of benign paroxysmal positional vertigo (BPPV) between older patients and young and middle-aged patients in the structured inquiry of dizziness history. Methods: The medical records of 6 807 patients diagnosed with BPPV from the Vertigo Database of Vertigo Clinical Diagnosis, Treatment, and Research Center of Beijing Tiantan Hospital, Capital Medical University, between January 2019 and October 2021 were retrospectively analyzed. The data included basic demographic information, clinical symptoms in a structured medical history questionnaire, and the time interval from the appearance of BPPV symptoms to diagnosis consultation. The patients were divided into the young and middle-aged group (<65 years old) and the older group (≥65 years old). The differences in clinical symptoms and consultation time were compared between these two groups. Categorical variables were represented by numbers (%), and compared using Chi-squared tests or Fisher's exact probability test for analysis; whereas, continuous variables conforming to normal distribution were represented by mean±standard deviation. Both data groups were compared and analyzed by Student's t-test. Results: The mean age of the older group was 65-92 (71±5) years, while the mean age of the middle-aged group was 18-64 (49±12) years. The incidence of vertigo (42.5% vs. 49.1%, χ2=23.69, P<0.001); vertigo triggered by changes in position of the head or body (52.4% vs. 58.7%, χ2=22.31, P<0.001); and autonomic symptoms (10.1% vs. 12.4%, χ2=7.09, P=0.008) were lower, but hearing loss (11.8% vs. 7.8%, χ2=27.36, P<0.001) and sleep disorders (18.5% vs. 15.2%, χ2=11.13, P=0.001) were higher in the older group than in the young and middle-aged group. The time from the appearance of dizziness to diagnosis was commonly longer in the older patient group than the other group (55.0% vs. 38.5%, χ2=55.95, P<0.001). Conclusions: Older patients with BPPV have more atypical symptoms and complex concomitant symptoms than young and middle-aged patients. For older patients with dizziness, positional testing is needed to confirm the possibility of BPPV even if the clinical symptoms are atypical.

Passion fruit peel and its zymolyte enhance gut function in Sanhuang broilers by improving antioxidation and short-chain fatty acids and decreasing inflammatory cytokines.

The passion fruit peel (PFP) is the by-product of juice processing and is rich in phenolic compounds and dietary fibers. As the high ADF content in PFP (34.20%), we proceeded to treat PFP with cellulase. The ADF decreased to 16.70% after enzymatic processing, and we supposed that enzymolytic passion fruit peel (EPF) should have a greater growth performance than PFP to broilers. Two trials were conducted to evaluate the effects of dietary PFP or EPF supplementation on growth performance, serum biochemical indices, meat quality, and cecal short-chain fatty acids, microbiota, and metabolites in broilers. In Exp. 1, 180 1-day-old Sanhuang broilers (male, 36.17 ± 2.47 g) were randomly allocated into 3 treatments, with 6 replicates in each treatment. The 3 experimental diets included 1 basal diet (control) and 2 PFP-added diets supplemented with 1 and 2% PFP, respectively. The trial lasted for 42 d. In Exp. 2, 144 Sanhuang broilers (male, 112-day-old, 1.62 ± 0.21 kg) were randomly allocated to 3 treatments. Each treatment was distributed among 6 pens, and each pen contained 8 broilers. The 3 treatment diets included: a control diet, a positive control diet supplementing 75 mg/kg chlortetracycline, and the experimental diet supplementing 3% EPF. The trial lasted for 56 d. Results showed that dietary 1 and 2% PFP addition did not affect growth performance in Exp. 1, and the 3% EPF supplementation had a negative effect on ADFI (P < 0.05) in Exp. 2. A decreased serum triglyceride (P < 0.05) in broilers was observed in Exp. 1. Broilers fed EPF had a higher glutathione peroxidase (GSH-Px) (P < 0.05), and lower levels of tumor necrosis factor-α (TNF-α) (P < 0.05) and glucose (P < 0.05) in Exp. 2. We also found that broilers from PFP or EPF-treated treatments had an increased butyrate content and higher microbial diversity in the cecum. The effects of antioxidation, anti-inflammatory function, and elevated SCFAs were confirmed after the microbe and untargeted metabolomic analysis. Dietary EPF supplementation significantly increased the SCFA-generating bacteria, anti-inflammatory-related bacteria, the antioxidant-related and anti-inflammatory-related metabolites. Moreover, dietary 3% EPF addition positively affects the biosynthesis of phenylpropanoids, which strongly correlate with the antioxidant and anti-inflammatory properties. In conclusion, the proper addition level did not affect the growth performance, and the PFP and EPF could improve the antioxidation state, anti-inflammatory activity, and intestinal functions of Sanhuang broilers to some extent.

[Phase Separation of Purified Human LSM4 Protein].

Liquid-liquid phase separation of proteins occur in a number of biological processes, such as regulation of transcription, processing, and RNA maturation. Sm-like protein 4 (LSM4) is involved in multiple processes, including pre-mRNA splicing and P-bodies assembly. Before investigating the involvement of LSM4 in the separation of the two liquid phases during RNA processing or maturation, the separation of the liquid phases in an in vitro preparation of LSM4 protein should be first be detected. The mCherry-LSM4 plasmid was derived from pET30a and used to isolate mCherry-LSM4 protein from prokaryotic cells (Escherichia coli strain BL21). The mCherry LSM4 protein was purified using Ni-NTA resin. The protein was further purified by fast protein liquid chromatography. Delta-Vision wide-field fluorescence microscopy was used to observe the dynamic liquid-liquid phase separation of the LSM4 protein in vitro. Analysis of the LSM4 protein structure using the Predictor of Natural Disordered Regions database revealed that its C-terminus contains a low complexity domain. A purified preparation of full-length human LSM4 protein was obtained from E. coli. Human LSM4 was shown to provide concentration-dependent separation of liquid-liquid phases in vitro in buffer with crowding reagents. Salts in high concentration and 1,6-hexanediol block the LSM4-induced separation of the two liquid phases. In addition, in vitro fusion of LSM4 protein droplets is observed. The results suggest that full-length human LSM4 protein can undergo liquid-liquid phase separation in vitro.

[Research advances on the mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis].

Wound healing involves complex pathophysiological mechanism, among which angiogenesis is considered as one of the key steps in wound healing, and promoting wound angiogenesis can accelerate wound healing. In recent years, mesenchymal stem cell-derived extracellular vesicles have been proven to produce equivalent effects of wound healing promotion comparable to stem cell therapy, with the advantages of low antigenicity and high biocompatibility. The specific mechanism by which extracellular vesicles facilitate wound healing is still not fully understood and is thought to involve all stages of wound healing. This article focuses on the possible mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis, so as to provide ideas for further study on the mechanism of extracellular vesicles to promote wound healing.

Bacterial antibiotic resistance among cancer inpatients in China: 2016-20.

BACKGROUND: The incidence of infections among cancer patients is as high as 23.2-33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. AIM: This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. DESIGN: This was a 5-year retrospective study on the antibiotic resistance of cancer patients. METHODS: In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. FINDINGS: Between 2016 and 2020, 216 219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. CONCLUSIONS: The bacterial prevalence and antibiotic resistance rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus and MRSA were significantly lower than the national average.

[Effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice].

Objective: To explore the effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice. Methods: The experimental research method was adopted. The control hydrogel composed of polyvinyl alcohol and gelatin, and the water-soluble chitosan hydrogel composed of the aforementioned two materials and water-soluble chitosan were prepared by the cyclic freeze-thaw method. The fluidity of the two dressings in test tube before and after the first freeze-thawing was generally observed, and the difference in appearance of the final state of two dressings in 12-well plates were compared. According to random number table (the same grouping method below), the cell strains of L929 and HaCaT were both divided into water-soluble chitosan hydrogel group and control hydrogel group, respectively. After adding corresponding dressings and culturing for 24 h, the cell proliferation activity was measured using cell counting kit 8. Rabbit blood erythrocyte suspensions were divided into normal saline group, polyethylene glycol octyl phenyl ether (Triton X-100) group, water-soluble chitosan hydrogel group, and control hydrogel group, which were treated accordingly and incubated for 1 hour, and then the hemolysis degree of erythrocyte was detected by a microplate reader. Twenty-four female db/db mice aged 11-14 weeks were selected, and full-thickness skin defect wounds on their backs were inflicted and inoculated with the methicillin-resistant Staphylococcus aureus (MRSA), 72 h later, the mice were divided into blank control group, sulfadiazine silver hydrogel group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. On post injury day (PID) 0 (immediately), 7, 14, and 21, the healing of the wound was observed. On PID 14 and 21, the wound healing rate was calculated. On PID 14, MRSA concentration in wounds was determined. On PID 21, the wounds were histologically analyzed by hematoxylin and eosin staining; the expression of CD31 in the wounds was detected by immunofluorescence method, and its positive percentage was calculated. Raw264.7 cells were taken and divided into interleukin-4 (IL-4) group, blank control group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. At 48 h of culture, the percentages of CD206 positive cells were detected by flow cytometry. The number of samples was all 3. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, least significant difference test, and Dunnett T3 test. Results: Two dressings in test tube had certain fluidity before freeze-thawing and formed semi-solid gels after freeze-thawing for once. The final forms of two dressings in 12-well plates were basically stable and translucent sheets, with little difference in transparency. At 24 h of culture, the cell proliferation activities of L929 and HaCaT in water-soluble chitosan hydrogel group were significantly higher than those in control hydrogel group (with t values of 6.37 and 7.50, respectively, P<0.01). At 1 h of incubation, the hemolysis degree of erythrocyte in water-soluble chitosan hydrogel group was significantly lower than that in Triton X-100 group (P<0.01), but similar to that in normal saline group and control hydrogel group (P>0.05). On PID 0, the traumatic conditions of mice in the 4 groups were similar. On PID 7, more yellowish exudates were observed inside the wound in blank control group and control hydrogel group, while a small amount of exudates were observed in the wound in sulfadiazine silver hydrogel group and water-soluble chitosan hydrogel group. On PID 14, the wounds in blank control group and control hydrogel group were dry and crusted without obvious epithelial coverage; in sulfadiazine silver hydrogel group, the scabs fell off and purulent exudate was visible on the wound; in water-soluble chitosan hydrogel group, the base of wound was light red and obvious epithelial coverage could be observed on the wound. On PID 14, the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 21, the wound in water-soluble chitosan hydrogel group was completely closed, while the wounds in the other 3 groups were not completely healed; the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 14, the concentration of MRSA in the wound in water-soluble chitosan hydrogel group was significantly lower than that in blank control group (P<0.01), but similar to that in control hydrogel group and sulfadiazine silver hydrogel group (P>0.05). On PID 21, the new epidermis was severely damaged in blank control group; the epidermis on the wound in control hydrogel group also had a large area of defect; complete new epidermis had not yet being formed on the wound in sulfadiazine silver hydrogel group; the wound in water-soluble chitosan hydrogel group was not only completely covered by the new epidermis, the basal cells of the new epidermis were also regularly aligned. On PID 21, the percentage of CD31 positivity in the wound in water-soluble chitosan hydrogel group was (2.19±0.35)%, which was significantly higher than (0.18±0.05)% in blank control group, (0.23±0.06)% in control hydrogel group, and (0.62±0.25)% in sulfadiazine silver hydrogel group, all P<0.01. At 48 h of culture, the percentage of CD206 positive Raw264.7 cells in water-soluble chitosan hydrogel group was lower than that in IL-4 group (P>0.01) but significantly higher than that in blank control group and control hydrogel group (P<0.05 or P<0.01). Conclusions: The water-soluble chitosan hydrogel has good biosafety and can induce higher level of macrophage M2 polarization than control hydrogel without water-soluble chitosan, so it can enhance the repair effect of MRSA-infected full-thickness skin defect wounds in diabetic mice and promote rapid wound healing.

Thermal management and control of wearable devices.

The emergence of wearable devices over the recent decades has motivated numerous studies aimed at developing flexible or stretchable materials and structures for their electronic or optoelectronic functionalities. Like in conventional devices, electronic and optoelectronic components in wearable devices must be kept within certain temperature ranges to ensure reliability, performance, and/or functionality. But this must be accomplished without requiring any bulky heat sinks or other heat transfer augmentation elements. At the same time, the proximity of wearable devices to the human skin poses additional requirements of thermal comfort and safety. A growing body of literature is now focusing on the thermal management or control of wearable devices and related development of new materials and structures. The present article aims to provide a broad overview of such materials and structures and offer suggestions for future research directions.

[Association of DNA methylation of IFNG gene with no/low response to hepatitis B vaccine in children].

Objective: To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province. Methods: A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti-HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results: There were 104 children in the case group and 159 in the control group. The median (Q1, Q3) level of anti-HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group (P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 (OR=1.18, 95%CI: 1.03-1.35) and 93 (OR=1.21, 95%CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion: The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

[Clinical features of epilepsy in 5 children with Mowat-Wilson syndrome].

Objective: To summarize and investigate the clinical characters of epilepsy in children with Mowat-Wilson syndrome (MWS), thus to improve the understanding of this disease. Methods: Clinical characters of epilepsy episodes in 5 children with MWS admitted to Department of Pediatrics, Peking University First Hospital from June to December 2020 were retrospectively reviewed. Clinical data including onset age of seizures, clinical features, characters of electroencephalogram (EEG), magnetic resonance imaging (MRI) findings, results of ZEB2 gene testing and responses to the anti-seizure medications (ASM) were summarized. Results: The onset age of seizures in the 5 patients (3 males and 2 females) ranged from 6 months to 4 years. Four patients showed focal motor seizures with diverse expressions, while the other 1 patient had epileptic spasms. All the 5 patients showed distinctive face, different degrees of intellectual disability, development delay and other congenital malformations. EEG of 4 patients presented the slowing of background rhythm and epileptiform discharges mainly occurred in the posterior region of the brain. The other 1 patient showed hypsarrhythmia at the beginning of the disease, changing into multifocal discharges mainly occurred in posterior region later. Corpus callosum abnormality and white matter disability were found from investigations of MRI in 2 patients, respectively. All the 5 patients carried a de novo heterozygous variation in the ZEB2 gene, 4 were nonsense variants and 1 was frame-shift variant. Within the follow-up of 14 months to 20 months, 3 patients achieved seizure-free more than 1 year, 2 patients achieved seizure-free more than 6 months. Two patients used valproate only and 2 patients received valproate combined with other ASM. Conclusions: Epileptic seizures are common clinical phenotype of MWS. Focal motor seizure may be the most common seizure type and epileptic spasms exist. The manifestations of EEG can be age-related. The most common type of variation of the ZEB2 gene is de novo nonsense variation. Valproate might be the first-line ASM for patients with MWS.

[METTL27 is a prognostic biomarker of colon cancer and associated with immune invasion].

OBJECTIVE: To investigate the expression and gene function of methyltransferase-like protein 27 (METTL27) in colon cancer, its association with immune infiltration and its prognostic significance. METHODS: We analyzed the expression levels of METTL27 in 33 cancers using R language and identified METTL27 as a differential gene in colon cancer. The related signaling pathways of METTL27 were analyzed by gene functional annotation and enrichment. SsGSEA algorithm was used to analyze immune infiltration, and logistic analysis was used to evaluate the correlation between METTL27 expression and clinicopathological features of the patients. Kaplan-meier analysis, univariate and multivariate Cox regression analysis were performed to construct a nomogram for evaluating the correlation between METTL27 expression and clinical prognosis. The expression level of METTL27 was further verified in colorectal cancer cell lines and 16 clinical specimens of colorectal cancer tissues using qPCR and Western blotting. RESULTS: METTL27 was highly expressed in 21 cancers, and its expression was significantly higher in colon cancer than in adjacent tissues (P < 0.001). METTL27-related genes were identified by differential analysis, and functional annotation revealed that METTL27 was significantly enriched in transmembrane transport and lipid metabolism, and 5 related signaling pathways were identified by GSEA. METTL27 expression was negatively correlated with different T helper cells and central memory T cells (P < 0.001). The patients with a high METTL27 mRNA expression had a poor survival outcome. Cox regression analysis showed that METTL27 expression was an independent prognostic factor of the overall survival. The expression level of METTL27 was significantly higher in the colorectal cancer cell line than in normal cells (P < 0.05). CONCLUSION: METTL27 is overexpressed in colon cancer and is associated with a poor prognosis of the patients. A high expression of METTL27 showed is associated less T cell immune infiltration, suggesting the potential of METTL27 as a prognostic marker of colon cancer.

Desalinating a real hyper-saline pre-treated produced water via direct-heat vacuum membrane distillation.

Membrane distillation (MD) is an emerging thermal desalination technology capable of desalinating waters of any salinity. During typical MD processes, the saline feedwater is heated and acts as the thermal energy carrier; however, temperature polarization (as well as thermal energy loss) contributes to low distillate fluxes, low single-pass water recovery and poor thermal efficiency. An alternative approach is to integrate an extra thermal energy carrier as part of the membrane and/or module assembly, which can channel externally provided heat directly to the membrane-feedwater interface and/or along the feed channel length. This direct-heat delivery has been demonstrated to increase single-pass water recovery and enhance the overall thermal efficiency. We developed a bench-scale direct-heated vacuum MD (DHVMD) process to desalinate pre-treated oil and gas "produced water" with an initial total dissolved solids of 115,500 ppm at a feed temperature ranging between 24 and 32 °C. We evaluated both water flux and specific energy consumption (SEC) as a function of water recovery. The system achieved a 50% water recovery without significant scaling, with an average flux >6 kg m-2 hr-1 and a SEC as low as 2,530 kJ kg-1. The major species of mineral scales (i.e., NaCl, CaSO4, and SrSO4) that limited the water recovery to 68% were modeled in terms of thermodynamics and identified by scanning electron microscopy and energy-dispersive X-ray spectroscopy. In addition, we further developed and employed a physics-based process model to estimate temperature, salinity, water transport and energy flows for full-scale vacuum MD and DHVMD modules. Model results show that a direct-heat input rate of 3,600 W can increase single-pass water recovery from 2.1% to 3.1% while lowering the thermal SEC from 7,800 kJ kg-1 to 6,517 kJ kg-1 in an unoptimized module. Finally, the scaling up potential of DHVMD process is briefly discussed.

Prevalence and potential risk factors of chronic pruritus among community middle-aged and older population in Beijing, China.

BACKGROUND: Chronic pruritus is a common problem among older adults, with a significant impact on their quality of life. However, it is under-studied epidemiologically, especially among Chinese older adults. OBJECTIVE: The aim of this study was to identify the prevalence and explore the risk factors of chronic pruritus among the middle-aged and older adults in Beijing, China. METHODS: A total of 929 participants aged ≥35 years from six communities in Beijing, China, were interviewed. The survey collected the demographic characteristics, the experience of chronic pruritus (>6 weeks), chronic disease history, the level of physical activities and sleep quality. A population-based case-control study was conducted, including 178 chronic pruritus cases and 697 controls. A multivariate logistic regression model was performed to explore the risk factors of chronic pruritus. Additionally, a random forest algorithm was used to rank the importance of potential risk factors and analyse the overall interpretation of risk factors. RESULTS: The prevalence of chronic pruritus was 19.48% (181/929) among the Beijing middle-aged and elderly population. The findings indicated that older adults aged 65 years old or above, male, with college or higher degree, alcohol drinking, hypertension, hyperlipidaemia, chronic lung disease, cardiovascular disease, digestive system disease and osteoarthritis/rheumatism, and middle or low sleep quality were associated with the increased risk of chronic pruritus respectively. Physical activity level (≥3000 Met) was associated with a decreased risk of chronic pruritus. The rank according to the most contribution of chronic pruritus risk was sleep quality, education, physical activity level, osteoarthritis/rheumatism, age and gender. CONCLUSION: Prevalence of chronic pruritus was high among the Chinese middle-aged and elderly population. Age, gender, high education, alcohol drinking, hypertension, hyperlipidaemia, chronic lung disease, cardiovascular disease, digestive system disease, osteoarthritis /rheumatism and poor sleep quality may serve as risk factors of chronic pruritus. Moderate and high physical activity levels may serve as protective factors of chronic pruritus risk.

Effects of Urban Particulate Matter on the Olfactory System in a Mouse Model.

BACKGROUND: Exposure to urban particulate matter (UPM) is linked to the aggravation of various health problems. Although the nasal cavity is the first barrier to encounter UPM, there is a lack of studies on the impact of UPM on the olfactory area. The purpose of this study was to investigate the cytotoxic effects of UPM on mouse olfactory epithelium, the underlying pathophysiology involved, and changes in cytokine levels. METHODS: Mice were divided into 4 groups: control, 400UPM (administered 400 µg UPM daily; standard reference material 1649b; average particle diameter 10.5 µm) 1week, 400UPM 2weeks, and recovery 1week after 400UPM 2weeks (n = 10, 6, 6, and 6, respectively). Olfactory function was evaluated by conducting a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination, gene ontology, quantitative real-time polymerase chain reaction, and western blotting. RESULTS: Compared to those in the control group, olfactory marker protein, olfactory receptor 1507, adenylyl cyclase 3, and GNAL mRNA levels were lower and S-100, 2',3'-cyclic nucleotide 30-phosphodiesterase, nerve growth factor receptor-associated protein, brain-derived neurotrophic factor, and tachykinin receptor mRNA levels were higher in the 400UPM group olfactory neuroepithelium. There were no significant differences in neuroepithelial inflammatory marker levels between the 400UPM and saline group. CONCLUSIONS: UPM decreased olfactory function and might have cytotoxic effects on the olfactory epithelium. Olfactory ensheathing cells and trigeminal nerve might be related to the regeneration of the olfactory epithelium after olfactory destruction associated with UPM.

Reverse-translational identification of a cerebellar satiation network.

The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control1-3. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a 'bedside-to-bench' approach for the identification of neural circuits that influence behaviour.