Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing

Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium, Akkermansia, and Lactobacillus and the decreases of Butyricimonas, Parabacteroides, and Anaeroplasma. Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
Mice ; Animals ; Gastrointestinal Microbiome ; Tripterygium ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Mice, Inbred C57BL ; Arthritis, Experimental/drug therapy*

Objective:To investigate the effects of different small monitor unit (MU) beam deletion optimization method in the CyberKnife treatment planning system on the calculated planned dose to brain tumors.Methods:A total of 17 patients with brain metastases treated in our hospital from June, 2021 to February, 2022 were selected for this study. A treatment plan was designed for each patient using the multiPlan system in the CyberKnife VSI system as the group without optimization. To improve the efficiency, the generated original plans should be optimized first by deleting some small MUs, forming an experience group and an optimization group for each patient. For the experience group, beams below 30 MU were deleted according to experience. For the optimization group, beams below the MU value calculated based on the second derivative method were deleted. Finally, the parameters of the two groups were statistically compared. The main evaluation parameters included the node number, the beam number, the total number of MUs, the estimated treatment duration, doses to 2% and 95% planning target volumes (PTV D2 and PTV D95), average dose to PTV ( Dmean), average dose to brain tissue ( Dmean-Brain), conformity index (CI), new conformity index (nCI), gradient index (GI), coverage, and the maximum doses to the brainstem and left and right lens ( Dmax-BS, Dmax-LL, and Dmax-RL), and the average doses to the dose shells 20 mm and 40 mm away from PTV (Shell20 and Shell40). Results:The two optimization method met the requirements for the prescription dose delivery to more than 98% PTV. There were statistical differences in the node number ( H = 7.97, P< 0.05) and estimated treatment duration ( H = 6.60, P < 0.05) among the group without MP optimization, the experience group, and the optimization group, with the estimated treatment duration and node number of the optimization group less than those of the group without MP optimization ( P < 0.05). There were no statistically significant differences in other parameters among the three groups ( P > 0.05). The PTV was moderately positively correlated with the treatment duration ( r=0.79, P < 0.01) and beam number ( r=0.78, P < 0.01) of the experience group, and was also moderately positively correlated with the treatment duration ( r=0.69, P < 0.01) and beam number ( r=0.71, P < 0.01) of the optimization group. Conclusions:For the CyberKnife planning of heads, the small MU beam deletion optimization method based on the second derivative can further shorten the treatment duration while ensuring no significant differences in the distribution of doses to organs at risk and targets. Moreover, this method is more effective in optimizing the plans for a large PTV volume.

Objective:To summarize the clinical characteristics and experiences in the diagnosis and treatment of congenital tuberculosis.Methods:This study involved four infants with congenital tuberculosis diagnosed in Guangdong Women and Children Hospital from January 2010 to January 2020. Moreover, publications of 52 congenital tuberculosis cases from Chinese hospitals between January 1994 and January 2019 were retrieved from Wanfang Database, China National Knowledge Infrastructure and PubMed. Clinical data of all patients were retrospectively analyzed.Results:All four cases we reported here were preterm infants with the onset of the disease at 14-30 d after birth and received anti-tuberculosis treatment. The interval between disease onset and diagnosis was 1-34 d. One baby was cured, one was improved, while the other two died. The median age at the onset of the disease in these 56 cases (including the four we reported and 52 from literature) was 14.5 d (7.0-20.7 d) and the median interval between the onset and diagnosis was 10.5 d (7.5~22.0 d). Forty-eight (88.9%) out of the 54 mothers were suffered from active tuberculosis during the perinatal period, including 16 diagnosed before delivery. The main clinical symptoms in these neonates were fever (82.1%, 46/56), respiratory distress (69.6%, 39/56), drowsiness and/or irritation (57.1%, 32/56), cyanosis (53.6%, 30/56), feeding difficulties (53.6%, 30/56), hepatomegaly (48.2%, 27/56) and splenomegaly (41.1%, 23/56). The positive rates of acid-fast staining, culture and polymerase chain reaction detection of Mycobacterium tuberculosis in sputum smears or gastric juice were all less than 33.3%, and the positive rate of spot test for Mycobacterium tuberculosis infection was 7/12. Chest X-ray showed miliary nodules and diffused nodules-patchy in 37.0% (20/54) and 25.9% (14/54) of the patients, respectively. Abdominal ultrasonography found 52.4% (11/21) with hepatomegaly and/or splenomegaly and 47.6% (10/21) with multiple low-density nodules in liver and spleen. The misdiagnosis rate was 28.6% (16/56). The overall mortality rate was 51.8% (29/56). However, the figure was 28.9% (11/38) in infants with anti-tuberculosis treatment and 18/18 in those without. Conclusions:Nonspecific clinical manifestations of congenital tuberculosis, together with low detection rate through laboratory tests, may lead to a higher rate of misdiagnosis and mortality. Therefore, a comprehensive assessment of the mothers of infants with suspected congenital tuberculosis is necessitated. Diagnosis and effective anti-tuberculosis treatment as early as possible are essential to improve the prognosis.

Objective To explore the research state and topics of lung cancer with chronic obstructive pulmonary disease (COPD) in China using the visualization methods. Methods Literature about lung cancer with COPD was searched through WanFang, CNKI, CBM, PubMed, The Cochrane Library and EMbase databases from inception to March 2018 by computer. We used BICOMS software to analyze the main information and produce co-word matrix, gCLUTO software to cluster, and NetDraw and Cytoscape software to draw the pictures. Results There were 304 studies related to lung cancer with COPD which originated from 173 journals including 23 indexed by Chinese Science Citation Database (CSCD) with 42 articles published, accounting for 13.8% of the total number of studies. There were 37 articles from 24 journals indexed by Science Citation Index (SCI) accounting for 12.2% of the total number of studies. The studies grew rapidly since 2012. The study involved 32 provinces, municipalities, and autonomous regions, among which Beijing, Sichuan, Shanghai, Guangzhou and Jiangsu provinces and cities were the main research areas. Sixty-nine high-frequency keywords were obtained with frequency 2 as the threshold, which was clustered into 5 categories by dual cluster analysis. Among them, topic 0 showed pathogenesis and radiological diagnosis of lung cancer with COPD, topic 1 was about the clinical characteristics of different pathological types of lung cancer with COPD and Chinese medicine treatment, topic 2 aimed at the impact of risk factors on surgical complications and the relationship between chemotherapy or targeted therapies and patient survival prognosis, topic 3 involved the pigenetic correlation between lung cancer and COPD and topic 4 was about clinical studies of perioperative comprehensive management of lung cancer patients with COPD. Conclusion The bibliometrics results show that there are considerable-amount achievements on lung cancer combined with COPD in China, and the researches have gradually increased since 2012. Horizontal research topics are extensive, and the focus of the study is to explore the perioperative comprehensive management and basic research of lung cancer with COPD, but the longitudinal themes need to be further studied. The results of some studies have not yet reached a consensus. There are few high-quality multi-center studies and a lack of clinical-directed achievement.

Objective: To improve synchrony tracking components of CyberKnife (tracking vest and tracking markers) and to analyze the clinical application value of the improved tracking components in CyberKnife treatment of thoracic and abdominal tumors. Methods: The tracking apron was made of knitted four-side elastic spandex cloth and suture design of Velcro, which was used to stick the tracking markers on the chest and abdomen of patients. The tracking markers added a 2 cm thick light foam block to the bottom of the original markers, and then the hook face of the Velcro was fixed to the bottom of the light foam. The improved trace component (the improved component) and the original component (the vendor component) were applied to the lung tracking treatment model, and the manufacturer components were included in the reference group. Adoption of improved components into the observation group; 20 different types of respiratory waveforms were simulated and applied to the same mold plan. After treatment, the coverage rate, mean standard deviation, maximum standard deviation and the slope of XYZ-axis vs. R correlation graph were recorded. The relevant parameters of Synchrony model and wearable time of two components were compared, and the application significances of the improved tracking component in the breathing tracking process of the CyberKnife were evaluated. Results: The maximum slope [median(interquartile range)] of XYZ-axis vs. R related graph in the reference group was 0.73 (3.89), 0.27 (0.49) and 0.34 (1.02), respectively. The maximum slope of XYZ-axis vs. R related graph in the observation group was 0.70 (2.78), 0.31 (0.30) and 0.36 (0.75), respectively. There was no statistically significant difference in the slope of XYZ-axis vs. R between the reference group and the observation group (all P > 0.05). There was no significant difference in the average standard error and maximum standard error between the reference group and the observation group [(1.7±0.4) mm vs. (1.7±0.5) mm, t=-0.382, P= 0.710; (2.0±0.6) mm vs. (1.7±0.5) mm, t=-0.877, P= 0.401], and the difference of the model coverage rate between the two groups was statistically significant [(48±18)% vs. (60±22)%, t= 2.762, P= 0.042]. The setup time of tracking components in the observation group was less than that in the reference group, and the difference was statistically significant [(44±24) s vs. (81±15) s, t=-4.310, P= 0.001]. Conclusions The improved tracking components are comparable to the manufacturer tracking components in the standard error of the Synchrony model. The improved components shorten the wear time and appropriately improve the coverage of the Synchrony model.

OBJECTIVETo explore the effects of acupuncture on the expression of protein kinase B (PKB/AKT) in lung tissues of asthma rats.

METHODSForty SPF male SD rats were randomly divided into a blank group, a model group, an acupuncture group and a blocker group, 10 rats in each one. The rat model of asthma was established by egg albumin stimulation in the model group, acupuncture group and blocker group. Since the establishment of rat model, the rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14), "Feishu" (BL 13) and "Fengmen" (BL 12) before atomization; the rats in the blocker group were treated with intervention of blocker LY294002, once every two days, for 7 times. There was no treatment in the blank group and model group. HE staining was applied to observe the morphologic changes of lung tissues; the immunohistochemical method was applied to test the protein expression of AKT in lung tissue.

RESULTSHE staining indicated the infiltration and aggregation of a variety of inflammatory cells around airways, as well as bronchial smooth muscle spasm and confined lumen in the model group; in the acupuncture group and blocker group the inflammatory cells were less and confined lumen was relieved. Compared with the blank group, the protein expression of AKT was higher in the model group (<0.05); compared with the model group, the protein expression of AKT in the acupuncture group and blocker group was reduced (both<0.05); the differences between the acupuncture group and blank group, blocker group were not significant (both>0.05).

CONCLUSIONSAcupuncture could reduce the protein expression of AKT in lung tissue in asthma rats, leading to relieved inflammation reaction and airway remodeling.

OBJECTIVETo explore the regulation of acupuncture for transforming growth factor β1 (TGF-β1) expression in the lung tissues of bronchial asthmatic rats.

METHODSForty SPF male SD rats were randomly divided into a blank group, a model group, an acupuncture group and a shallow fast acupuncture group, 10 rats in each group. Asthma model was established in the model, acupuncture, and shallow fast acupuncture groups, and no intervention was applied in the blank and model groups. Before atomization excitation, 20 min acupuncture was applied at "Dazhui" (GV 14) "Feishu" (BL 13) "Fengmen" (BL 12) in the acupuncture group. Acupuncture only into skin without needle retained at the above acupoints was used in the shallow fast acupuncture group before atomization excitation from the day of model established. All the treatment was given 7 times, once the other day. The pathological lunge tissues of rats were observed by HE staining; the protein expression of TGF-β1 in the lung tissues was examined by immunohistochemical staining and immunofluorescence staining. The TGF-β1 expressions in bronchoalveolar lavage fluid (BALF) and serum were showed by ELISA.

RESULTSThere were changes in the lung tissues in the model group, including mucus plug in the bronchial lumen, irregular bronchial epithelium, thick airway smooth muscle, local break, narrow lumen, a large number of inflammatory cell infiltration. The phenomena in the acupuncture group were improved and those in the shallow fast acupuncture group were not apparently changed compared with those in the model group. The IOD value of TGF-β1 expression in the model group increased compared with that in the blank group (<0.05); the positive expression in the acupuncture group was lower than those in the model and shallow fast acupuncture groups (both<0.05). The contents of TGF-β1 in BALF and serum of the acupuncture group were lower than those in the model and shallow fast acupuncture groups (all<0.05).

CONCLUSIONSAcupuncture may improve airway inflammatory response and remolding of asthma by inhibiting TGF-β1 expression.

The inhibitory effect of NACOS on dyslipidemia and potential molecular mechanisms by in vitro and in vivo experiments were investigated. For in vitro study, four experimental groups were designed by using HepG2 cells, including the control group, palmitic acid (PA) treatment alone group, NACOS treatment alone group and NACOS + PA treatment group. For in vivo study, male C57BL/6 mice were divided into four groups (n=5) at random including the normal control group (NCD), high fat diet (HFD) group, NACOS treatment alone group, NACOS+HFD group, which were treated for 20 weeks. The used methods in this study were as follows: the observation of lipid droplet deposition in HepG2 cells by oil red O staining, the detection of mRNA levels of lipid metabolism-related regulators and inflammatory cytokine by RT-PCR method, the monitoring of MAPKs and PI3K/Akt pathway activation by Western blotting method. The in vitro study shows that, NACOS had no toxicity on the viability of HepG2 cells at 25-100 μg/mL and significantly reduced the deposition of lipid droplet. Also, based on both in vitro and in vivo investigation, NACOS evidently down-regulated the expression of lipid metabolism-related regulators (PGC1α, Cox5b, Mcad) and inflammatory cytokine (IL-1β) at mRNA level (P<0.05 or 0.01), and suppressed the activation of p38, ERK1/2 and Akt in HepG2 cells and lever tissues from HFD-fed mice (P<0.05 or 0.01). Based on the above, NACOS may inhibit the oxidation of liver mitochondrial fatty acid and the lipid biosynthesis, block the inflammatory responses and prevent the HepG2 cells and C57BL/6 mice from lipidemia.

Objective To evaluate the diagnostic value of ultrasound-guided fine needle aspiration cytology(US-FNAC)in the assessment of radiologically detected ovarian neoplasms and retroperitoneal metastatic lymph nodes. Methods FNAC was performed under ultrasound guidance on 126 patients suspected of ovarian neoplasms and retroperitoneal metastatic lymph nodes. Cytologic examination was performed after staining smears with the haematoxylin and eosin method. Clinical data were retrieved from the medical records and all cytological specimens were reviewed. In these cases, the cytologic findings were correlated with histology of the primary tumor and were compared with surgical pathology. Results Satisfactory sampling was obtained in 86.2% of punctures, and cytological diagnosis was made in 85.7% cases. The size of the lymph nodes punctured was less than 20 mm in 93.5% cases, with the sensitivity of 81.6%、86.2%, specificity of 95.8%、100.0%, positive predictive value of 98.3%、100.0%, negative predictive value of 63.9%、33.3%, and accuracy of 85.3%、87.1%. Seven patients presented slight abdominal discomfort, and relieved without clinical treatment. Conclusions The fine needle aspiration technique has excellent positive predictive value and low morbidity. US-FNAC, as the valuable investigation, is not only useful in the diagnosis of ovarian masses and lymph nodes but can also help in choosing appropriate management. From our experience, US-FNAC can be added in follow-up of selected patients in whom the cytological identification of such masses and nodes is significant for the patient′s treatment.