Volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) are common organic compounds in indoor and outdoor air, and enter the human body primarily through the respiratory tract and directly damage the respiratory system. Previous studies have suggested that exposure to VOCs/SVOCs may associate with the prevalence, incidence, and progression of asthma, but the extent of the associations is still vague. Furthermore, biomarkers for efficient and simple asthma diagnosis, typing, and attack prediction remain unclear at this stage. From the perspective of the collection and detection methods of VOCs/SVOCs, this paper summarized the epidemiological associations and underlying biological mechanisms between VOCs/SVOCs exposure and the prevalence, incidence, and progression of asthma in children/adults. It also demonstrated the application of VOCs/SVOCs in recent years in assisting asthma diagnosis, such as distinguishing asthma patients from the healthy population, differentiating different asthma phenotypes, and predicting asthma acute exacerbations, aiming to provide a scientific basis for improving current asthma management.

ObjectiveTo analyze stroke mortality data from Yuyao, Zhejiang Province, from 2015 to 2022, and to provide references for the development of effective stroke prevention and control strategies in Yuyao and similar county-level cities or districts. MethodsData on all stroke-related deaths in Yuyao from 2015 to 2022 were collected. Metrics including crude mortality rate (CMR), Chinese-standardized mortality rate, world-standardized mortality rate, truncated mortality rate (35‒64 years), cumulative mortality rate (0‒74 years), premature mortality rate, potential years of life lost (PYLL), average years of life lost (AYLL), PYLL rate (PYLLR), and average annual percentage change (AAPC) were calculated. Differences between groups were compared using the Chi-square test. Linear regression was utilized to calculate AAPC and analyze mortality trends. ResultsFrom 2015 to 2022, a total of 6 533 stroke deaths were recorded among residents in Yuyao, with ischemic stroke accounting for 70.60% and hemorrhagic stroke accounting for 29.40%. The average CMR was 97.67/100 000, China-standardized mortality rate was 45.82/100 000, and world-standardized mortality rate was 32.10/100 000. No statistically significant differences were observed in CMR, China-standardized morality rate, or world-standardized mortality rate over the 8 years (all P>0.05). Stroke deaths primarily occurred in winter (from December to February of next year), accounting for 31.21% of the cases. Male stroke mortality rate (108.15/100 000) was significantly higher than female mortality rate (87.49/100 000, χ²=73.195, P<0.001). Stroke mortality rate increased significantly with age (χ²_trend=17 839.150, P<0.001), peaking at 1 867.82/100 000 in the ≥85-year-old age group. Hemorrhagic stroke mortality rate was higher than ischemic stroke mortality rate in the 10‒64-year-old age group, whereas ischemic stroke mortality rate exceeded hemorrhagic stroke mortality rate in those aged 65 years and above. The PYLL caused by stroke mortality was 11 014.00 person-years, with an AYLL of 10.98 years, and a PYLLR of 1.87‰. ConclusionStroke mortality in Yuyao has remained relatively stable. A community-based comprehensive chronic disease intervention mechanism should be established, with a focus on males and the elderly. This mechanism should integrate community health education, stroke risk assessment, screening and intervention, two-way patient referral systems, and tiered rehabilitation services to reduce mortality rate and mitigate life expectancy loss.

Objective To prepare paclitaxel-natural borneol complex,and to explore the prescription and preparation process of paclitaxel-natural borneol complex drug-loaded submicroemulsion,and its in vitro anti-tumor effect.Methods The Paclitaxel-natural borneol complex was prepared by grinding method and identified by Fourier Transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC).The compound drug-loaded submicroemulsion was prepared using a two-step high-pressure emulsification method.The single-factor investigation and the orthogonal experimental design were applied to optimize the formulation and preparation process.MTT assay,cell cloning assay,and cell scratch assay were used to evaluate the effect of this preparation on HCT-116 cells.Results The infrared spectral absorption peaks of taxol-natural borneol complex at 3 312.76 cm-1 and 3 513.92 cm-1 disappeared,and DSC analysis showed that a new absorption peak of taxol-natural borneol complex appeared at 154.56 ℃,indicating that taxol be coupled with natural borneol to form a new complex.The optimal prescription was 0.44％active pharmaceutical ingredient[paclitaxel-natural borneol(1∶3)],10％medium chain triglyceride,3％emulsifier[egg yolk lecithin-Poloxam 188(1∶2)],2％glycerol,0.3％oleate.The optimal process was emulsification at 80 ℃,60 MPa high pressure homogenization 10 times.The half inhibitory concentration(IC50)was 0.75 μg·mL-1 by MTT asssy in cell.In the cell cloning assay,the scratch healing area of blank control group,paclitaxel raw material and paclitaxel/natural borneol submicroemulsion were(36.44±3.35)％,(13.59±9.28)％,(8.30±4.09)％,respectively.The results were statistically significant(P＜0.05).In the plate cloning experiment,the cell cloning rates of blank control group,paclitaxel bulk drug group and submicroemulsion group were(37.92±0.729)％,(9.16±1.335)％and(3.36±1.065)％,respectively,the differents were statistically significant(P＜0.05).Conclusion This submicroemulsion has reasonable prescription,feasible process and good stability.Cell experiments showed that the submicronemulision effectively inhibits the proliferation and migration of HCT-116 cells,suggesting its potential as a promising antitumor agent.

Objective:To observe the effect of warming needle therapy combined with Tuina(Chinese therapeutic massage)on the clinical symptoms and anxiety state of patients with cervical vertigo accompanied by anxiety. Methods:Seventy patients with cervical vertigo accompanied by anxiety state were divided into an observation group and a control group using the random number table method,with 35 patients in each group.In addition to disease education,the observation group was treated with warming needle therapy and Tuina 3 times a week,and the control group was treated with betahistine mesylate tablets orally 3 times a day.Both groups were treated for 4 weeks.The changes in the scores of the evaluation scale for cervical vertigo(ESCV),self-rating anxiety scale(SAS),and Hamilton anxiety rating scale(HAMA)were compared between the two groups after treatment. Results:One case in the observation group dropped out due to failure to cooperate with the treatment during the study.In the treatment group,the total effective rate and the cured plus markedly effective rate were 94.1%and 50.0%,respectively,and 88.6%and 8.6%in the control group,respectively;the differences between the two groups were statistically significant(P<0.05).After treatment,the ESCV,SAS,and HAMA scores of both groups decreased significantly compared with those before treatment(P<0.01),and the scores of the observation group were lower than those of the control group(P<0.01 or P<0.05). Conclusion:Warming needle therapy combined with Tuina can significantly improve the clinical symptoms of patients with cervical vertigo accompanied by anxiety state.

OBJECTIVE: To investigate the role and underlying mechanism of human myeloid differentiation protein 2 (MD2) in the process of neuronal death induced by lipopolysaccharide (LPS) by establishing an in vitro model of sepsis-associated encephalopathy (SAE) by LPS. METHODS: Healthy C57BL/6J mice at 14-18 days of gestation were selected, and brain cortical tissue was taken from fetal mice. Neurons were stimulated with 0 (control), 1, 5 and 10 g/L of LPS for 24 hours. The release of lactate dehydrogenase (LDH) was detected and the death of neurons was observed. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukins (IL-6, IL-1β), in order to determine the optimal dose of LPS for establishing an in vitro neuroinflammation model of SAE. The cells were divided into blank control group and LPS group. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) was used to discover apoptosis. Western blotting was used to detect the expression of the relevant protein markers activated caspase-3, necroptosis-associated protein neuronal receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and phosphorylated RIPK3 (p-RIPK3). Immunofluorescence chemical staining was used to detect the expressions of p-RIPK3 and microtubule-associated protein 2 (MAP2) to evaluate the type of cell death and the degree of neuronal death. Western blotting was used to detect MD2 expression. Immunofluorescence chemical staining was performed to observe the expression and distribution of p-RIPK3 and MD2 in neurons to assess whether MD2 was involved in the inflammatory response promoting neuronal death. In addition, the cells were divided into blank control group, LPS group, and MD2 interfering peptide group (LPS+TC group), and the levels of IL-6, IL-1β and LDH were detected to evaluate whether interfering with MD2 can alleviate LPS induced neuroinflammation. RESULTS: 10 g/L LPS induced notable neuronal death, and the release of LDH in neurons stimulated with this concentration for 24 hours was significantly higher than that in the blank control group (relative release: 1.45±0.04 vs. 1.00±0.00, P < 0.01), indicating apoptosis and necroptosis occurred in neurons, and the levels of inflammatory factors IL-6 and IL-1β were remarkable increased [IL-6 (relative level): 1.94±0.04 vs. 1.00±0.00, IL-1β (relative level): 1.53±0.09 vs. 1.00±0.00, both P < 0.01]. Compared with the blank control group, the apoptosis of cells, cleaved-caspase-3 expression, the p-RIPK3/RIPK3 ratio, and p-RIPK3 expression around neurons in the LPS group were significantly increased [cleaved-caspase-3/GAPDH: 1.55±0.10 vs. 1.00±0.00, P < 0.01; p-RIPK3/RIPK3 ratio (relative value): 1.54±0.06 vs. 1.00±0.00, P < 0.05], which suggested that typical apoptosis and necroptosis apoptosis occurred in neurons in the septic environment. Furthermore, MD2 expression was significantly increased in the LPS group compared with the blank control group (MD2/GAPDH: 1.91±0.07 vs. 1.00±0.00, P < 0.01), and MD2 expression around neurons was increased, indicating that LPS-induced MD2 upregulation may play a key role in neuroinflammation and induction of neuronal death in sepsis. In addition, compared with the LPS group, the MD2-interfering peptide could reduce the expression levels of inflammatory factors IL-6 and IL-1β [IL-6 (relative level): 1.16±0.08 vs. 1.94±0.04, IL-1β (relative level): 1.15±0.05 vs. 1.75±0.09, both P < 0.01] and decrease LDH release (relative release: 1.09±0.01 vs. 1.44±0.04, P < 0.05). CONCLUSIONS LPS induced neuronal inflammatory responses via MD2, which ultimately leads to apoptosis and necroptosis. Interfering with MD2 reduces inflammation and inhibits neuronal death.
Mice ; Humans ; Animals ; Sepsis-Associated Encephalopathy ; Caspase 3 ; Interleukin-6 ; Neuroinflammatory Diseases ; Lipopolysaccharides ; Mice, Inbred C57BL ; Cell Differentiation ; Tumor Necrosis Factor-alpha

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Objective:To evaluate the outcomes of aortic root repair in acute type A aortic dissection (ATAAD) with aortic sinus involvement.Methods:The clinical data of patients with ATAAD involving the aortic sinus and an aortic root diameter of ≤45 mm who were treated from January 1, 2015, to December 31, 2016, were collected. Patients were divided into group A (involvement of one aortic sinus or part of one aortic sinus) and group B (involvement of more than one aortic sinus). The effectiveness of aortic root repair in ATAAD with sinus involvement was analyzed by comparing the preoperative imaging characteristics and postoperative results between the two groups.Results:The study cohort comprised 155 patients, including 100 patients in group A and 55 in group B. There were no differences between the two groups in baseline characteristics, aortic root diameter, 30-day mortality, and complication rates. During an average follow-up of(49.1±14.6) months, there was no difference between the two groups in the survival rate (92.0% vs. 89.5%, P=0.61). The aortic root diameter at follow-up showed no progressive expansion compared with preoperatively in either of the two groups[(38.1±3.6) mm vs. (37.9±3.5)mm, P=0.92, A; (38.4±4.1) mm vs. (38.3±3.6) mm, P=0.74, B]; furthermore, there was no difference between the two groups in aggravation of aortic regurgitation. Conclusion:Aortic root repair achieves satisfactory medium-term outcomes in ATAAD with more than one aortic sinus involved, but the long-term outcomes need to be evaluated.

Objective:To investigate the clinical value of conventional ultrasound combined with automated breast volume scanner (ABVS) in predicting axillary lymph node metastasis (ALNM) of patients with invasive ductal carcinoma.Methods:A retrospective analysis was performed in 96 patients in the General Hospital of Eastern Theater Command from January 2014 to December 2020. All patients were examined by conventional ultrasound and ABVS before treatment. The patients were divided into the ALNM group and non-axillary lymph node metastasis (N-ALNM) group according to the postoperative pathological results. The differences of ultrasound parameters between the two groups were compared, and Logistic regression was used to analyze the independent predictive factors of ALNM. The ROC curve was plotted to evaluate the diagnostic efficacy for ALNM.Results:Compared with the N-ALNM group, the ALNM group had the characteristics of larger long diameters, unclear boundary, uneven internal echo, Adler blood flow grade Ⅱ-Ⅲ and retraction phenomenon (all P<0.05). Logistic regression analysis showed that the long diameter, uneven internal echo, and retraction phenomenon were independent predictors of ALNM ( OR=1.051, 4.055, 3.493, all P<0.05). The area under curve of ALNM was 0.752(0.653-0.834), the sensitivity and specificity were 54.7% and 83.7%, respectively. Conclusions:The long diameter, uneven internal echo, and retraction phenomenon measured by conventional ultrasound and ABVS are independent predictors of ALNM. The combination of the three can provide imaging references for the evaluation of ALNM of breast cancer.

Venous thromboembolism(VTE)is a high mortality disease involving multiple factors, and public hospitals assume the main responsibility for the diagnosis and treatment of VTE. Based on the concept of taking patients as the center, Zhejiang Provincial People′s Hospital improved the system design and digital level, and carried out digital practices such as patient timeline management, high-risk patient management, VTE special disease bank, and auxiliary decision-making system. The hospital evaluation rate and prevention rate continued to increase, the follow-up effect was good, and the workload of medical staff was reduced and satisfaction rate was improved.

The existing doctor-patient communication pattern often falls prey to insufficient informed consent and even medical disputes. In the patient centered perspective, Zhejiang Provincial People′s Hospital explored a new communication mode centering on patients. Based on diagnosis-related groups catalogues and high-frequency surgeries catalogues of the departments, multimedia technology was called into play to produce dubbed PPTs and videos that were easy to understand, standardized and homogeneous, which were embedded into medical records system. Following observation of the PPT or video, patients could directly sign an informed consent on the computer. This practice not only deepens patient′s understanding and achieves homogeneous level of the communication, but also elevates doctor′s work efficiency, contributing to building a harmonious doctor-patient relationship.