An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

Neoadjuvant therapy has been widely applied in the treatment of rectal cancer, which can shrink tumor size, lower tumor staging and improve the prognosis. It has been the standard preoperative treatment for patients with locally advanced rectal cancer. The efficacy of neoadjuvant therapy for rectal cancer patients varies between individuals, and the results of tumor regression are obviously different. Some patients with good tumor regression even achieve pathological complete response (pCR). Tumor regression is of great significance for the selection of surgical regimes and the determination of distal resection margin. However, few studies focus on tumor regression patterns. Controversies on the safe distance of distal resection margin after neoadjuvant treatment still exist. Therefore, based on the current research progress, this review summarized the main tumor regression patterns after neoadjuvant therapy for rectal cancer, and classified them into three types: tumor shrinkage, tumor fragmentation, and mucin pool formation. And macroscopic regression and microscopic regression of tumors were compared to describe the phenomenon of non-synchronous regression. Then, the safety of non-surgical treatment for patients with clinical complete response (cCR) was analyzed to elaborate the necessity of surgical treatment. Finally, the review studied the safe surgical resection range to explore the safe distance of distal resection margin.
Humans ; Neoadjuvant Therapy/methods* ; Margins of Excision ; Treatment Outcome ; Rectal Neoplasms/pathology* ; Rectum/pathology* ; Neoplasm Staging ; Retrospective Studies

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.
Adult ; Male ; Child ; Female ; Humans ; Adolescent ; Young Adult ; Middle Aged ; Aged ; DNA Copy Number Variations ; Osteosarcoma/pathology* ; Mutation ; DNA, Neoplasm ; High-Throughput Nucleotide Sequencing ; Bone Neoplasms/pathology* ; Nucleotides

Objective To investigate the effects and mechanisms of TAR DNA-binding protein 43(TDP-43)on oxygen-glucose deprivation(OGD)-induced apoptosis in mouse atrial myocytes(HL-1 cells).Methods The in vitro cultured mouse atrial myocytes(HL-1 cells)were divided into:(1)control group and groups with different OGD treatment times(2,4,8,16 h),and cell viability was detected by CCK-8 assay,and TDP-43 protein expression level was detected by Western blotting,which was used to determine the time point of OGD induction for the subsequent study;(2)control and OGD groups,flow cytometry was used to detect apoptosis,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect adenosine triphosphate(ATP)relative content,microplate method to detect malondialdehyde(MDA)content,and WST-1 method to detect superoxide dismutase(SOD)content.Mouse atrial myocytes(HL-1 cells)transfected with lentivirus were divided into:(1)negative control lentiviral intervention group(NC-shRNA),TDP-43 knockdown lentiviral intervention group(TDP-43-shRNA1,TDP-43-shRNA2,TDP-43-shRNA3),and Western blotting was used to detect the TDP-43 protein expression level,and the group with the highest lentiviral knockdown efficiency was selected as the TDP-43-shRNA for subsequent experiments;(2)NC-shRNA group,TDP-43-shRNA group,OGD+NC-shRNA group,OGD+TDP-43-shRNA group,under normoxic and OGD conditions,flow cytometry was used to detect the apoptosis rate,MitoTracker staining to detect mitochondrial morphology,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect the relative content of ATP,flow cytometry to detect the fluorescence intensity of reactive oxygen species(ROS),microplate to detect the content of MDA,and WST-1 to detect the content of SOD.Results CCK-8 method showed that,with the prolongation of OGD time,the viability of mouse atrial myocytes(HL-1 cells)gradually decreased;Western blotting assay showed that the expression level of TDP-43 protein gradually increased,and both of them showed a strong time-dependence.Compared with control group,mouse atrial myocytes(HL-1 cells)viability was the lowest(P<0.05)and TDP-43 protein expression was the highest(P<0.05)at 16 h of OGD,accordingly,OGD 16 h was chosen as the induction time point for subsequent experiments.Compared with control group,the apoptosis rate,the fluorescence intensity ratio of mitochondrial membrane potential and the content of MDA increased,the relative content of ATP and SOD decreased in OGD group,and the differences were all statistically significant(P<0.05).Western blotting detection showed that compared with NC-shRNA group,the TDP-43-shRNA2 group had the most obvious reduction in TDP-43 protein expression level(P<0.05)and the highest knockdown efficiency,so the TDP-43-shRNA2 group was selected for subsequent experiments.The results of flow cytometry showed that under normoxic conditions,there was no significant change in the apoptosis rate in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);and under OGD conditions,the apoptosis rate in OGD+TDP-43-shRNA group reduced when compared with OGD+NC-shRNA group(P<0.05).MitoTracker staining results showed that the mitochondrial morphology of TDP-43-shRNA group was intact without significant changes compared with NC-shRNA group;the mitochondria of OGD+NC-shRNA group increased in number,most of which were fragmented and scattered in distribution;compared with OGD+NC-shRNA group,the mitochondrial morphology of OGD+TDP-43-shRNA group was restored.Under normoxic conditions,there were no significant changes in mitochondrial membrane potential,relative ATP content,ROS fluorescence intensity,MDA content,and SOD content in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);however,under OGD conditions,the ratio of fluorescence intensity of mitochondrial membrane potential of cells the fluorescence intensity of ROS,and the content of MDA decreased,and the relative content of ATP and the content of SOD increased in OGD+TDP-43-shRNA group compared with that of OGD+NC-shRNA group,and all of these differences was statistically significant(P<0.05).Conclusion TDP-43 exacerbates OGD-induced mitochondrial dysfunction by regulating cardiomyocyte apoptosis;therefore,knockdown of TDP-43 expression is expected to be a potential therapeutic strategy for ischemic cardiomyopathy.

Objective: To investigate the occupational hazard factors and exposure levels of workers during the construction of power transmission and transformation projects. Methods: Analysis and identification of occupational hazard factors were carried out for typical construction process of 6 power transmission projects and 3 substation projects in September 2018. The on-site occupational health investigation was carried out to detect and analyze the exposure levels of workers to occupational hazard factors. Results: The time weighted average concentration (C(TWA)) of crushing workers exposed to silica dust and welders exposed to welding fume in substation projects were 2.72 and 14.03 mg/m(3), respectively. The 8 h equivalent sound level results of exposure noise of carpenters in power transmission projects and crushing workers, reinforcement workers, carpenters, scaffolders, road builders in substation projects were 87.9, 92.5, 87.1, 92.5, 93.0 and 90.2 dB (A) , respectively. The 4-hour time equal energy frequency weighted vibration acceleration of hand-transmitted vibration of bricklayer in power transmission projects, bricklayer, general worker 3, road builder 1 and road builder 2 of substation projects were 5.36, 5.21, 5.28, 10.71 and 5.22 m/s(2), respectively. The effective irradiance of electric welding arc light of welders' limbs in power transmission projects and substation projects were 401.19, 319.68 μW/cm(2), respectively. All of the above exceeded the requirements of occupational exposure limits. The occupational radiation levels and exposure limits of hazardous chemical factors met the requirements of each post. Conclusion: During the construction of power transmission and transformation projects, the exposure levels of occupational hazard factors in multiple posts exceed the standard. The main responsibility of employers for occupational disease prevention and control should be implemented, and targeted comprehensive measures should be taken to reduce the exposure levels of occupational hazard factors of workers.
Dust ; Humans ; Occupational Diseases ; Occupational Exposure/analysis* ; Occupational Health ; Welding

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.
Anastomotic Leak/surgery* ; Humans ; Intestinal Obstruction/surgery* ; Laparoscopy ; Postoperative Complications/surgery* ; Prospective Studies ; Rectal Diseases/surgery* ; Rectal Neoplasms/surgery* ; Retrospective Studies ; Syndrome ; Treatment Outcome

Objective: The characteristics of 3D-FLAIR MRI images of the inner ear of patients with vestibular neuritis were preliminarily studied to explore the possible pathogenesis of vestibular neuritis, and the correlation analysis was conducted in combination with vestibular function to provide a basis for accurate diagnosis of vestibular neuritis. Methods: A total of 36 patients with vestibular neuritis (VN) from December 2019 to October 2020 were collected from the Vertigo Department of Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University. There were 36 cases (18 females, 18 males) with unilateral acute vestibular neuritis, 17 cases of left ear and 19 cases of right ear. According to the results of 3D-FLAIR MRI in the inner ears, the patients were divided into the enhanced group and the non-enhanced group (the health side served as the normal control group). The results of vestibular function examination in the two groups were compared. SPSS19.0 software was used for statistical processing to analyze the relationship between the vestibular function and the characteristics of 3D-FLAIR imaging in the inner ears. Results: Abnormal enhancement of 3D-FLAIR was found in 31 cases (86.1%) of the 36 cases, including 14 cases of both vestibular nerve and vestibular terminal organ enhancement, eight cases of superior vestibular nerve enhancement alone, seven cases of vestibular terminal organ enhancement alone, and two cases of cochlear enhancement alone. Observation of abnormal reinforcement of vestibular nerve showed: twenty-one cases of superior vestibular nerve reinforcement, one case of superior and inferior vestibular nerve reinforcement. No abnormalities were found in 3D-FLAIR of inner ear in 5 cases. According to the analysis of vestibular function results, there were 19 cases (52.8%) with total vestibular involvement, sixteen cases (44.4%) with superior vestibular involvement alone, and one case (2.8%) with inferior vestibular involvement alone. Comparison of vestibular function between the five cases (non-enhancement group) and the 31 cases (enhanced group) in the 3D-FLAIR group of the inner ears showed that the CP values of caloric tests in the enhanced group were higher (60.81±3.49 vs 34.12±7.37), with statistically significant difference (t=-2.898, P<0.01). Conclusion: In patients with vestibular neuritis, 3D-FLAIR MRI scan of the inner ear provides visual imaging evidence for clinical practice, considering that the lesion site of vestibular neuritis is not only in the vestibular nerve, but also in the vestibular end organ. Patients with 3D-FLAIR enhanced in the inner ear may have more significant vestibular function damage.
Caloric Tests ; Female ; Humans ; Imaging, Three-Dimensional/methods* ; Magnetic Resonance Imaging/methods* ; Male ; Vestibular Neuronitis/diagnosis* ; Vestibule, Labyrinth

Humans ; Immune Checkpoint Inhibitors ; Myocarditis ; Myositis/chemically induced* ; Antineoplastic Agents, Immunological

OBJECTIVE: Chinese medicine has the potential to modulate allergic rhinitis (AR). There have been studies investigating the treatment efficacy of Yupingfeng San, alone or in combination with other ingredients, in AR, though few have studied the potential mechanisms of these drugs. In the present study, we measured the effects of Jiawei Yupingfeng (JWYPF), a traditional Chinese medicine formula, on mice with ovalbumin-induced AR and explored its underlying mechanism of action. METHODS: Forty BALB/c mice were randomly divided into normal control, allergy control and two treatment groups of ten mice each. In the normal control group, mice were sensitized and challenged with saline. The mice in the allergy control and treatment groups were sensitized and challenged with ovalbumin and aluminum hydroxide gel. The treatments of JWYPF and Nasonex were administered intranasally in the AR mice for one week. Several signs of allergic inflammation, such as nasal eosinophils and inflammatory cytokines, were measured to determine the underlying mechanisms. RESULTS: Mice in the JWYPF and Nasonex groups had significantly lower AR symptom scores than those in the allergy control group (the mean differences between JWYPF and the allergy control, and Nasonex and the allergy control were -2.00 ± 0.35 and -2.40 ± 0.32). After treatment with JWYPF and Nasonex, the levels of ovalbumin-specific IgE and histamine were significantly reduced, as were the levels of interlukin-4 and transforming growth factor-β, while interferon-γ levels were increased (all P < 0.0001, vs. allergy control). These two treatments also significantly inhibited eosinophil and mast cell infiltration into the nasal cavity but were not statistically different from one-another. CONCLUSION JWYPF has a potential therapeutic effect on AR via adjusting the rebalance of T helper 1 and T helper 2.
Animals ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred BALB C ; Rhinitis, Allergic/drug therapy*

COVID-19 ; Female ; Humans ; Infectious Disease Transmission, Vertical ; Pregnancy ; Pregnancy Complications, Infectious/drug therapy* ; Pregnancy Outcome ; Premature Birth ; Retrospective Studies ; SARS-CoV-2