Electropolishing influence on biocompatibility of additively manufactured Ti-Nb-Ta-Zr: in vivo and in vitro.

Balling defect of the additively manufactured titanium lattice implants easily leads to muscle tissue rejection, which might cause failure of implantation. Electropolishing is widely used in surface polishing of complex components and has potential to deal with the balling defect. However, a clad layer could be formed on the surface of titanium alloy after electropolishing, which may affect the biocompatibility of the metal implants. To manufacture lattice structured ß-type Ti-Ni-Ta-Zr (TNTZ) for bio-medical applications, it is necessary to investigate the impact of electropolishing on material biocompatibility. In this study, animal experiments were conducted to investigate the in vivo biocompatibility of the as-printed TNTZ alloy with or without electropolishing; and proteomics technology was used to elaborate the results. The following conclusions were drawn: (a) a 30% oxalic acid electropolishing treatment was effective in solving balling defects, and ~21 nm amorphous clad layer would be formed on the surface of the material after polishing; (b) the electropolished TNTZ suggested decreased cell cytotoxicity and improved blood biocompatibility as compared to as-printed TNTZ; (c) the amorphous clad layer could make a barrier to prevent Ta and Zr ions from penetrating into the muscle tissue, and could form a good tissue regeneration at the implantation site during 4 weeks, indicating that the electropolished TNTZ has the potential as implants; and (d) the cells attached to the electropolished TNTZ showed higher antioxidant capacity but less proliferation than attached to as-printed TNTZ.

[Clinicopathological features of NTRK3 gene rearrangement papillary thyroid carcinoma].

Objective: To investigate the clinicopathological features and differential diagnosis of NTRK3 gene rearrangement thyroid papillary carcinoma (PTC). Methods: The PTC cases without BRAF V600E mutation were collected at Fujian Provincial Hospital South Branch from January 2015 to January 2020. The cases of NTRK3 gene rearrangement PTC were examined using immunohistochemistry and fluorescence in situ hybridization (FISH). The clinical data, histopathological characteristics, immunohistochemical features and molecular pathological changes were retrospectively analyzed. Data from the TCGA PTC dataset and the literature were also studied. Results: A total of 3 PTC cases harboring NTRK3 gene rearrangement were confirmed. All the patients were female, aged from 26,49,34 years. Histologically, two of them demonstrated a multinodular growth pattern. Only one case showed prominent follicular growth pattern; the other two tumors showed a mixture of follicular, papillary and solid growth patterns. All tumors showed a typical PTC nuclear manifestation, with some nuclear pleomorphism, vacuolated foci and oncocytic features. The characteristic formation of glomeruloid follicular foci was present in two cases which also showed psammoma bodies, and tumoral capsular or angiolymphatic invasion. The background thyroid parenchyma showed chronic lymphocytic thyroiditis. Mitotic rates were low, and no cases had any tumor necrosis. The pan-TRK and TTF1 testing was both positive in 3 cases, while S-100 and mammaglobin were both negative in them. FISH studies confirmed the NTRK3 gene rearrangement in all 3 cases. Studies on the TCGA datasets and literature revealed similar findings. Conclusions: NTRK3 gene rearrangement PTC is rare. It may be easily misdiagnosed due to the lack of histological and clinicopathological characteristics. Molecular studies such as pan-TRK immunostaining, FISH and even next-generation sequencing are needed to confirm the diagnosis. Immunohistochemistry of pan-TRK performed in the PTC cases without BRAF V600E mutation can be used as a good rapid-screening tool. With the emergence of pan-cancer tyrosine receptor kinase inhibitors, proper diagnosis of these tumors can help determine appropriate treatments and improve their outcomes.

[Prognostic values of stromal tumor-infiltrating lymphocytes and lymphocyte-activation gene-3 in advanced gastric adenocarcinoma].

Objective: To analyze density of stromal tumor-infiltrating lymphocytes (sTIL) and expression of lymphocyte-activation gene-3 (LAG-3) protein in advanced gastric adenocarcinomas, and to investigate the correlation of sTIL and LAG-3 with the prognosis in patients with advanced gastric adenocarcinoma. Methods: The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected at Fujian Cancer Hospital, from January 2011 to December 2014. The percentage of sTILs was reported semi-quantitatively using histological section evaluation, the LAG-3 protein was detected using immunohistochemistry, and the expression was correlated with the clinicopathological features and patient outcomes. Results: Among the 260 cases, high density of sTIL was detected in 173 cases (66.5%) while LAG-3 high expression was observed in 160 cases (61.5%). These cases were divided into four groups. Group Ⅰ: 48 cases (18.5%) were sTIL low/LAG-3 low; group Ⅱ: 52 cases (20.0%) were sTIL high/LAG-3 low; group Ⅲ: 39 cases (15.0%) were sTIL low/LAG-3 high; group Ⅳ: 121 cases (46.5%) were sTIL high/LAG-3 high. Kaplan-Meier survival analyses showed that patient prognoses were related to age, tumor size, tumor location, Lauren classification, perineural invasion, vascular invasion, TNM staging, postoperative adjuvant chemotherapy and molecular classification (P<0.05). Meanwhile, higher densities of sTIL and higher expression of LAG-3 were associated with better prognosis. Multivariate survival analysis showed age, tumor size, Lauren classification and postoperative adjuvant chemotherapy were independent prognostic factors for patient survival. The results showed a poor prognosis in low-sTIL/low-LAG-3 patients. Conclusions: Compared with low density of sTIL and low expression of LAG-3, high density of sTIL and high expression of LAG-3 are associated with better outcomes in patients with advanced gastric adenocarcinoma, respectively. Combined detecton of sTIL and LAG-3 may be more useful in gastric cancer than using either alone. Age, tumor size, Lauren classification and postoperative adjuvant chemotherapy are independent prognostic factors for patients with advanced gastric adenocarcinoma.

Effects of guanidinoacetic acid and coated folic acid supplementation on growth performance, nutrient digestion and hepatic gene expression in Angus bulls.

To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA-) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA- diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA- diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.

Effects of copper sulphate and coated copper sulphate addition on lactation performance, nutrient digestibility, ruminal fermentation and blood metabolites in dairy cows.

Coated copper sulphate (CCS) could be used as a Cu supplement in cows. To investigate the influences of copper sulphate (CS) and CCS on milk performance, nutrient digestion and rumen fermentation, fifty Holstein dairy cows were arranged in a randomised block design to five groups: control, CS addition (7·5 mg Cu/kg DM from CS) or CCS addition (5, 7·5 and 10 mg Cu/kg DM from CCS, respectively). When comparing Cu source at equal inclusion rates (7·5 mg/kg DM), cows receiving CCS addition had higher yields of fat-corrected milk, milk fat and protein; digestibility of DM, organic matter (OM) and neutral-detergent fibre (NDF); ruminal total volatile fatty acid (VFA) concentration; activities of carboxymethyl cellulase, cellobiase, pectinase and α-amylase; populations of Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes; and liver Cu content than cows receiving CS addition. Increasing CCS addition, DM intake was unchanged, yields of milk, milk fat and protein; feed efficiency; digestibility of DM, OM, NDF and acid-detergent fibre; ruminal total VFA concentration; acetate:propionate ratio; activity of cellulolytic enzyme; populations of total bacteria, protozoa and dominant cellulolytic bacteria; and concentrations of Cu in serum and liver increased linearly, but ruminal propionate percentage, ammonia-N concentration, α-amylase activity and populations of Prevotella ruminicola and Ruminobacter amylophilus decreased linearly. The results indicated that supplement of CS could be substituted with CCS and addition of CCS improved milk performance and nutrient digestion in dairy cows.

Lesion-aware convolutional neural network for chest radiograph classification.

AIM: To investigate the performance of a deep-learning approach termed lesion-aware convolutional neural network (LACNN) to identify 14 different thoracic diseases on chest X-rays (CXRs). MATERIALS AND METHODS: In total, 10,738 CXRs of 3,526 patients were collected retrospectively. Of these, 1,937 CXRs of 598 patients were selected for training and optimising the lesion-detection network (LDN) of LACNN. The remaining 8,801 CXRs from 2,928 patients were used to train and test the classification network of LACNN. The discriminative performance of the deep-learning approach was compared with that obtained by the radiologists. In addition, its generalisation was validated on the independent public dataset, ChestX-ray14. The decision-making process of the model was visualised by occlusion testing, and the effect of the integration of CXRs and non-image data on model performance was also investigated. In a systematic evaluation, F1 score, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) metrics were calculated. RESULTS: The model generated statistically significantly higher AUC performance compared with radiologists on atelectasis, mass, and nodule, with AUC values of 0.831 (95% confidence interval [CI]: 0.807-0.855), 0.959 (95% CI: 0.944-0.974), and 0.928 (95% CI: 0.906-0.950), respectively. For the other 11 pathologies, there were no statistically significant differences. The average time to complete each CXR classification in the testing dataset was substantially longer for the radiologists (∼35 seconds) than for the LACNN (∼0.197 seconds). In the ChestX-ray14 dataset, the present model also showed competitive performance in comparison with other state-of-the-art deep-learning approaches. Model performance was slightly improved when introducing non-image data. CONCLUSION: The proposed LACNN achieved radiologist-level performance in identifying thoracic diseases on CXRs, and could potentially expand patient access to CXR diagnostics.

[Study on the incidence of adult herpes zoster in Yichang city and its association with early-life famine exposure].

Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83‰. The crude incidence rate of adult HZ in females (7.26‰) was higher than that in males (6.40‰). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ (OR=1.21; 95%CI: 1.01-1.45, P=0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females (OR=1.28, 95%CI:1.02-1.61, P=0.034).

Effects of rumen-protected folic acid and betaine supplementation on growth performance, nutrient digestion, rumen fermentation and blood metabolites in Angus bulls.

This study evaluated the effects of rumen-protected folic acid (RPFA) and betaine (BT) on growth performance, nutrient digestion and blood metabolites in bulls. Forty-eight Angus bulls were blocked by body weight and randomly assigned to four treatments in a 2 × 2 factorial design. BT of 0 or 0·6 g/kg DM was supplemented to diet without or with the addition of 6 mg/kg DM of folic acid from RPFA, respectively. Average daily gain increased by 25·2 and 6·29 % for addition of BT without RPFA and with RPFA, respectively. Digestibility and ruminal total volatile fatty acids of neutral-detergent fibre and acid-detergent fibre increased, feed conversion ratio and blood folate decreased with the addition of BT without RPFA, but these parameters were unchanged with BT addition in diet with RPFA. Digestibility of DM, organic matter and crude protein as well as acetate:propionate ratio increased with RPFA or BT addition. Ruminal ammonia-N decreased with RPFA addition. Activity of carboxymethyl cellulase, cellobiase, xylanase, pectinase and protease as well as population of total bacteria, protozoa, Fibrobacter succinogenes and Ruminobacter amylophilus increased with RPFA or BT addition. Laccase activity and total fungi, Ruminococcus flavefaciens and Prevotella ruminicola population increased with RPFA addition, whereas Ruminococcus albus population increased with BT addition. Blood glucose, total protein, albumin, growth hormone and insulin-like growth factor-1 increased with RPFA addition. Addition of RPFA or BT decreased blood homocysteine. The results indicated that addition of BT stimulated growth and nutrient digestion in bulls only when RPFA was not supplemented.

[Efficacy of olaparib combined with pembrolizumab in second-line treatment for extensive-stage small cell lung cancer].

Objective: To compare the efficacy and safety of olaparib in combination with pembrolizumab with pembrolizumab alone in second-line treatment for patients with extensive stage-small cell lung cancer (ES-SCLC) whose ages ranged from 40 to 80 years. Methods: From March 2017 to October 2019, 21 patients with progressed or relapsed small cell lung cancer after standard first line treatment were enrolled in this study. The olaparib/pembrolizumab group (n=11) was treated by olaparib 300mg twice per day combined with pembrolizumab 200mg once every 3 weeks, while pembrolizumab group was treated by pembrolizumab alone. Results: The objective response rate (ORR) of olaparib/pembrolizumab group and pembrolizumab group were 45.5% and 10.0%, respectively (P=0.149), and the disease control rate (DCR) were 81.8% and 70.0% (P=0.635). The median progression-free survival (PFS) were 5.93 months and 3.53 months (P=0.036), the median overall survival (OS) were 10.43 months and 8.43 months (P=0.063). The adverse reaction incidences of all grades were 90.9% and 70.0% (P=0.311), and the incidences of grade Ⅲ-Ⅴ including myelosuppression were 36.4% and 10.0% (P=0.311), gastrointestinal reaction were 9.1% and 10.0%, (P=1.000) and other immune-related adverse events were 18.2% and 30.0% (P=1.000). Further analysis showed the metastatic number (P=0.006), platinum sensitivity (P=0.036) and LDH level (P=0.022) significantly affected the ORR of olaparib/pembrolizumab therapy. Conclusion: Our preliminary study indicates that olaparib combined with pembrolizumab is an efficient and safe second-line treatment therapy for patients with ES-SCLC.

[Cyto-inactivation instantly induced by microwave ablation on thyroid nodules].

Objective: To explore the effect of microwave ablation on thyroid nodules cell activity by the reaction of key enzyme of cell activation. Methods: From November 2017 to February 2018, 104 patients with 120 thyroid nodules underwent ultrasound-guided microwave ablation at Super-minimally Invasive Medicals, Shanghai International Medical Center, aged 14-55 years, 42 males and 62 females.Twice core needle biopsy were performed before and after thermal ablation.The specimen were using hematoxylin and eosin (HE) staining and enzyme histochemical staining with include succinate dehydrogenase (SDH) and nicotinamide adeninedinucleotide phosphate diaphorase (NADPH-d), respectively, and observe under microscope. Results: Enzyme histochemical staining showed that the positive rate of SDH and NADPH-d in the marginal region and transitional region were 100% before ablation, and were 0% immediately after ablation.The positive rate of SDH and NADPH-d histochemical staining in the same area before and immediately after ablation was statistically significant (P<0.05). Shortly after microwave ablation, the tissue structure and cell morphology showed no obvious alteration in HE stained sections, but in sections with enzyme histochemical staining, the activity of SDH and NADPH-d in ablated tissue disappeared.The accuracy rate of pathologic diagnosis was 100% after ablation. Conclusions: SDH and NADPH-d enzyme activity may be better in evaluating the short-term efficacy of microwave ablation of thyroid nodules than HE staining.

[The diagnostic value of low dose of dual-source CT venography for deep venous thrombosis].

Objective: To investigate the diagnostic value of low dose of dual-source CT venography examination for DVT (deep venous thrombosis). Methods: A total of 60 patients from Nanjing First Hospital with suspected DVT underwent indirect low dose CTV examination and treatment of DSA from January to December, 2017, and recording the radiation dose for CTV.DSA as the gold standard, calculate the sensitivity, specificity of CTV, kappa consistency test was used to exam the results of CTV and DSA.McNemar test was used to check statistical difference between two examinations. Results: A total of 60 patients, 780 blood vessels took CTV examinations, 326 were positive; 420 blood vessels took DSA examinations, 332 were positive.DSA as the gold standard, the sensitivity, specificity, of DVT detection by CTV were 96.2% and 92.6%, kappa=0.860, P<0.05, and the result of McNemar test was P=0.263. Conclusion: Low dose of dual-source indirect CTV examination for DVT can not only reduce radiation dose for the patients, but also has a high clinical value in the diagnosis of DVT.

Severe vitamin D deficiency increases the risk for moderate to severe disease activity in Chinese patients with SLE.

OBJECTIVE: We aimed to investigate the prevalence of vitamin D deficiency in Chinese lupus patients and to assess the association between vitamin D levels and disease severity. METHODS: Serum levels of 25OHD3 in 121 patients with systemic lupus erythematosus (SLE) and 150 healthy controls were measured by electrochemiluminescence immunoassay. Data regarding demographics and clinical parameters were collected. Disease activity of SLE was evaluated according to the SLE Disease Activity Index (SLEDAI) score and irreversible organ damage by the Systemic Lupus International Collaborating Clinic/American College of Rheumatology, SLICC/ACR Damage Index (SDI). The multivariate logistic regression model was used to investigate the association between the degree of vitamin D deficiency and SLEDAI or SDI scores. RESULTS: The prevalence of vitamin D insufficiency (25OHD3 <30 ng/ml) and severe deficiency (25OHD3 <10 ng/ml) in SLE patients was 62.81% and 34.71%, respectively. Logistic regression analysis indicated that the cut-off point of 25OHD3 concentration was 10 ng/ml where its level was correlated with increased SLEDAI (OR 6.420, p = 0.006), but not with the SDI. In addition, hydroxychloroquine treatment lowered the SLEDAI increased by the severe 25OHD3 deficiency (OR 0.280, p = 0.008). Moreover, long disease duration (OR 1.014, p = 0.008) predicted moderate to severe organ damage. CONCLUSIONS: Vitamin D deficiency is highly prevalent in patients with SLE. Severe deficiency increases the risk for moderate to severe disease activity, but not for organ damage.

WNT10A polymorphism may be a risk factor for non-syndromic hypodontia.

This study was designed to determine whether polymorphisms in the gene wingless-type MMTV integration site family, member 10A (WNT10A) are associated with non-syndromic hypodontia (tooth agenesis). A case-control study was performed involving 129 subjects with sporadic non-syndromic hypodontia (cases) and 218 healthy individuals (controls). DNA was obtained from whole blood and the ligase detection reaction method was used to analyze two single nucleotide polymorphisms (SNPs) of the WNT10A gene. A significant difference between cases and controls was observed in the allele and genotype frequencies of both SNPs (rs116998555 and rs147680216). For rs116998555, the presence of the T allele (the thymine variant) was associated with tooth agenesis [odds ratio (OR) = 5.722; 95% confidence interval (CI) = 3.053-10.727; P < 0.001], while for rs147680216, the A allele (the adenine variant) correlated with this condition (OR = 2.665; 95%CI = 1.512-4.695; P < 0.001). We provide here the first case-control study evidence that risk of hypodontia may be related to the WNT10A polymorphism. Our results also confirm the importance of the Wnt pathway in tooth development.

[Association between efficacy and molecular subtypes in breast cancer patients receiving neoadjuvant chemotherapy].

OBJECTIVE: To investigate the association between pathological complete response (pCR), clinicopathological characteristics and clinical outcomes in breast cancer patients receiving neoadjuvant chemotherapy. METHODS: Medical records of 221 patients who underwent neoadjuvant chemotherapy for breast cancer between January 2006 and December 2008 were retrospectively reviewed. Their clinicopathological features, response to neoadjuvant chemotherapy, survivals and prognostic factors were then analyzed. RESULTS: The total pCR rate was 11.3% (25/221). The rate of pCR was 0%(0/12), 5.7%(6/106), 7.4%(2/27) and 16.9%(11/65) in the luminal A, luminal B, HER-2, and Basal-like subtypes, respectively. Statistically significant association was found between the pCR rate and the molecular substypes of breast cancer(P<0.05). The median 5-year disease free survival and the 5-year overall survival were 72 months and 79 months. The 5-year disease free survival rate and 5-year overall survival rate were 61.1% and 71.9% in all the 221 patients. The 5-year disease free survival rates of pCR and non-pCR patients were 84.0% and 58.2%, and the 5-year overall survival rates of pCR and non-pCR patients were 96.0% and 68.9%, respectively(P<0.05 for all). The multivariate survival analysis showed that clinical and pathological node stage and pCR are independent prognostic factors for the 5-year disease-free survival and 5-year total survival in patients with neoadjuvant chemotherapy (P<0.05 for both). CONCLUSIONS: pCR is more frequently observed in HER-2 and basal-like breast cancer subtypes compared with the luminal breast cancer subtype. The status of clinical and pathological node status and pCR are independent prognostic factors in patients treated with neoadjuvant chemotherapy.

[Metabolic syndrome and its influencing factors in professional automobile drivers in a company].

OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS)in 259 professional automobile drivers, and to put forward targeted suggestions on protection. METHODS: In October 2014, 114 male bus drivers and 145 male taxi drivers in a transportation service company were enrolled as investigation group, and 121 non-operating male staff were enrolled as control group. Physical examination and a questionnaire survey were conducted for both groups, and the results were analyzed. RESULTS: The bus drivers and taxi drivers had significantly higher prevalence rates of MS than the nonoperating staff(17.5%/13.1% vs 3.3%, P<0.05). The results of univariate logistic analysis showed that smoking(OR=2.58, 95%CI 1.14~5.88), exercise (OR=0.21, 95% CI 0.10~0.43), meal time (OR=0.27, 95% CI 0.13~0.59), and a family history of chronic diseases (OR=2.26, 95% CI 1.13~4.50)were associated with MS, and each independent variable showed significant differences between groups (P<0.05). Multivariate logistic regression analysis showed that with age remaining the same, smoking was the risk factor for MS in professional automobile drivers (OR=5.25, 95%CI 2.00~13.80), and meal time (20~40 min)(OR= 0.20, 95%CI 0.09~0.44)and exercise (OR=0.13, 95% CI 0.06~0.30)were protective factors against MS. CONCLUSION: Professional automobile drivers have a higher prevalence rate of MS than non-operating staff, which should be taken seriously by working personnel.

[An investigation of mental health in migrant workers in an enterprise].

Objective: To investigate the mental health status in migrant workers in a labor-intensive enterprise and related influencing factors. Methods: Typical sampling was used to perform an investigation in 910 migrant workers in a large foreign-funded labor-intensive enterprise in Shenzhen, China. All the respondents gave informed consent and completed the questionnaire independently and anonymously. The self-reported mental health status was evaluated using the Beck Anxiety Inventory, Beck Depression Inventory, and General Health Questionnaire. Results: Of all the migrant workers in this enterprise, 7.2% had a positive self-reported anxiety symptom, 25.4% had a moderate or severe self-reported depression symptom, and 76.4% had a poor self-reported general health status. Age had significant influence on the self-reported depression symptom (χ2=21.968, P<0.05) ; age did not have significant influence on the self-reported anxiety and general health status (χ2=6.616、12.498, both P>0.05) . The knowledge of occupational hazards had significant influence on mental health status (χ2Depression=47.289, χ2General health=21.087, both P<0.05) . The feeling of work had significant influence on self-reported depression and general health status (χ2Depression=52.406, χ2General health=17.327, both P<0.05) . Attention to self mental health had significant influence on self-reported depression (χ2=17.714, P<0.05) , and whether the person wanted to learn the knowledge of mental health had significant influence on self-reported anxiety (χ2= 6.145, P<0.05) . Conclusion: The self-reported mental health status in migrant workers is poor and is associated with age, worry about exposure to occupational hazard factors, emphasis on mental health knowledge, and a focus on personal mental health. Therefore, targeted occupational health education and occupational mental health education should be strengthened.

Brain targeting efficacy of novel drug delivery system in the treatment of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group. MATERIALS AND METHODS: Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration. RESULTS: The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration. CONCLUSIONS: This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.

[Biosafety risk of laboratory-acquired infection and countermeasures based on human factors].

Biosafety of pathogenic microbiology laboratories generally highlights the use of protective equipment, procedures, and operating practices to protect personnel and the environment from potentially hazardous biological materials. Under the current complex situation where traditional and non-traditional biosafety issues coexist, laboratory-acquired infection (LAI) of pathogenic microorganisms may cause illness, disability and even death. Pathogenic microorganisms may also be carried to the surrounding environment, causing community infection, which should be taken seriously. Analysis of LAI cases helps to understand the causes of exposure and learn lessons from post-exposure prophylaxis to be prepared and even prevent problems before they happen. Human factors cause most LAIs, laboratory activities related to aerosolization, laboratory activities related to sharps materials, low ability of personnel performing the work, and deficiencies in laboratory facilities or management are the four main factors. This study focuses on the human factors that lead to LAI, combined with confirmed cases, discusses the biosafety risks of pathogenic microorganism laboratories, reviews the development and evolution of biosafety laboratories and the current protection measures for experimenters, and accordingly puts forward countermeasures and suggestions.

Tertiary Lymphoid Structure Raises Survival and Immunotherapy in HPV- HNSCC.

Immune checkpoint blockade (ICB) targeting PD-1/PD-L1 has been used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the overall response rate to ICB therapy for HNSCC remains less than 20%. It has recently been reported that the appearance of tertiary lymphoid structures (TLSs) in tumor tissue is correlated with better prognosis and response to ICB treatment. Here, we demonstrated an immune classification for the tumor microenvironment (TME) of HNSCC by analyzing The Cancer Genome Atlas (TCGA)-HNSCC data set and found that immunotype D with TLS enrichment had a better prognosis and response to ICB treatment. Furthermore, we observed that TLSs were present in a part of tumor samples of human papillomavirus (HPV) infection negative HNSCC (HPV- HNSCC) and were associated with the densities of dendritic cell (DC)-LAMP+ DCs, CD4+ T cells, CD8+ T cells, and progenitor T cells in TME. We established an HPV- HNSCC mouse model with TLS-enriched TME by overexpressing LIGHT in a mouse HNSCC cell line. We found that the induction of TLS formation enhanced the response to PD-1 blockade treatment in the HPV- HNSCC mouse model, accompanied by increases in DCs and progenitor exhausted CD8+ T cells in the TME. Elimination of CD20+ B cells attenuated the therapeutic effect of PD-1 pathway blockade in TLS+ HPV- HNSCC mouse models. These results indicate that TLSs contribute to the favorable prognosis and antitumor immunity of HPV- HNSCC. Inducing TLS formation in HPV- HNSCC tumors is a potential therapeutic method for improving the ICB response rate in patients with HPV- HNSCC.