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Whole-exome sequencing identified novel DNAH5 homozygous variants in two consanguineous families with primary ciliary dyskinesia

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中华医学杂志(英文版) 2024年第1期137卷 115-116页

作者： Yang Binyi Lei Cheng Xu Yingjie Yang Danhui Lu Chenyang Liu Ying guo ting Luo Hong Department of Pulmonary and Critical Care Medicine The Second Xiangya Hospital 3. Central South University 4. Changsha 5. Hunan 410011 6. China

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive inherited disease characterized by dysfunction of the motile cilia. DNAH5, the most frequently mutated gene in PCD, encodes a heavy chain of the ciliary outer dynein arms (ODAs). Herein, we report two patients with Kartagener syndrome (sinusitis, bronchiectasis, and situs inversus) in two consanguineous families carrying two novel homozygous DNAH5 variants [Supplementary Figures 1A and 1B, http://***/CM9/B598].

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Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

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World Journal of Clinical Cases 2024年第3期12卷 575-581页

作者： Qing-Qing Dou ting-ting Sun guo-Qiang Wang Wei-Bing Tong Graduate Student Institute Inner Mongolia Medical UniversityHohhot 010000Inner Mongolia Autonomous RegionChina Central Breast Area B Beijing University Cancer Hospital Inner Mongolia HospitalHohhot 010000Inner Mongolia Autonomous RegionChina

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that

关键词： Breast cancer brain metastasis Resistance to trastuzumab Macromolecule inetetamab Small molecule tyrosine kinase inhibitor Radiation therapy HER2-positive Case report

Molybdenum and cadmium co-induce necroptosis through Th1/Th2 imbalance-mediated endoplasmic reticulum stress in duck ovaries

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Journal of Environmental Sciences 2024年第8期142卷 92-102页

作者： ting Cui Xueyan Dai Huiling guo Dianyun Wang Bingyan Huang Wenjing Pu Xuesheng Chu Caiying Zhang Jiangxi Provincial Key Laboratory for Animal Health Institute of Animal Population HealthCollege of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 330045China

Cadmium(Cd)and excess molybdenum(Mo)pose serious threats to animal health.Our previous study has determined that Cd and/or Mo exposure can cause ovarian damage of ducks,while the specific mechanism is still obscure.To further investigate the toxic mechanism of Cd and Mo co-exposure in the ovary,forty 8-day-old female ducks were randomly allocated into four groups for 16 weeks,and the doses of Cd and Mo in basic diet per kg were as follows:control group,Mo group(100 mg Mo),Cd group(4 mg Cd),and Mo+Cd group(100 mg Mo+4 mg Cd).Cadmium sulfate 8/3-hydrate(CdSO_(4)·8/3H_(2)O)and hexaammonium molybdate((NH_(4))_(6)Mo_(7)O_(24)·4H_(2)O)were the origins of Cd and Mo,respectively.At the 16th week of the experiment,all ovary tissues were collected for the detection of related indexes.The data indicated that Mo and/or Cd induced trace element disorders and Th1/Th2 balance to divert toward Th1 in the ovary,which activated endoplasmic reticulum(ER)stress and then provoked necroptosis through triggering RIPK1/RIPK3/MLKL signaling pathway,and eventually caused ovarian pathological injuries and necroptosis characteristics.The alterations of above indicators were most apparent in the joint group.Above all,this research illustrates that Mo and/or Cd exposure can initiate necroptosis through Th1/Th2 imbalance-modulated ER stress in duck ovaries,and Mo and Cd combined exposure aggravates ovarian injuries.This research explores the molecular mechanism of necroptosis caused by Mo and/or Cd,which reveals that ER stress attenuation may be a therapeutic target to alleviate necroptosis.

关键词： Molybdenum Cadmium Th1/Th2 imbalance Endoplasmic reticulum stress Necroptosis Ovary

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Higher intakes of lysine,threonine and valine are inversely associated with non-alcoholic fatty liver disease risk:a community-based case-control study in the Chinese elderly

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Food Science and Human Wellness 2024年第1期13卷 191-197页

作者： Xueqi Li Wenjun Ma ting Yang Chong Wang Wei Zhang Hui Li ting Zhao Xiaofei guo Institute of Nutrition&Health School of Public HealthQingdao UniversityQingdao 260071China Affiliated Hospital of Qingdao University Qingdao 260071China

The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearityting against NAFLD in the elderly.

关键词： Amino acid Non-alcoholic fatty liver disease Senior citizen Dose-response analysis

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Metal-Free Synthesis of 2-Aminobenzothiazoles via I2-Catalyzed Tandem Cyclization Reaction of Amines and Carbon Disulfide

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Chinese Journal of Chemistry 2024年第8期42卷 846-852页

作者： ting Chen Wei Feng Ruitong Yang Shanping Chen guo-Jun Deng Key Laboratory for Green Organic Synthesis and Application of Hunan Province Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of EducationCollege of ChemistryXiangtan UniversityXiangtanHunan411105 China School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiangHunan453007 China

Comprehensive Summary,A convenient approach for the construction of 2-aminobenzothiazoles via I2-catalyzed tandem cyclization reaction of amines and carbon disulfide has been developed.The present approach starts from simple and readily available starting materials,affording a series of 2-aminobenzothiazoles in up to 89%yields under metal-free conditions.In this work,C—H/N—H functionalization was achieved and multiple C-hetero bonds were successfully constructed in one pot.

关键词： Sulfur heterocycles C-H functionalization Cyclization Tandem reaction Transition-metal-free Amines lodine N-Heterocycles

N-doping offering higher photodegradation performance of dissolved black carbon for organic pollutants: experimental and theoretical studies

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第4期25卷 340-356页

作者： Yong guo Mengxia CHEN ting CHEN Ying guo Zixuan XU guowei XU Soukthakhane SINSONESACK Keophoungeun KANMANY Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes Ministry of EducationCollege of EnvironmentHohai UniversityNanjing 210093China Key Laboratory of Environmental Engineering of Jiangsu Province Jiangsu Provincial Academy of Environmental ScienceNanjing 210036China State Key Laboratory of Pollution Control and Resource Reuse Nanjing UniversityNanjing 210023China Central Environmental Laboratory Natural Resources and Environment Research InstituteMinistry of Natural Resources and EnvironmentVientiane 999012Laos

We investigated the influence mechanism of N-doping for dissolved black carbon(DBC)photodegradation of organic pollutants.The degradation performance of N-doped dissolved black carbon(NDBC)for tetracycline(TC)(71%)is better than that for methylene blue(MB)(28%)under irradiation.These levels are both better than DBC degradation performances for TC(68%)and MB(18%)under irradiation.Reactive species quenching experiments suggest that h and-O,are the main reactive species for NDBC photodegraded TC,while-OH and h*are the main reactive species for NDBC photodegraded MB.-OH is not observed during DBC photodegradation of MB.This is likely because N-doping increases valence-band(VB)energy from 1.55 eV in DBC to 2.04 eV in NDBC;the latter is strong enough to oxidize water to form-OH.Additionally,N-doping increases the DBC band gap of 2.29 to 2.62 eV in NDBC,resulting in a higher separation efficiency of photo-generated electrons-holes in NDBC than in DBC.AIl these factors give NDBC stronger photodegradation performance for TC and MB than DBC.High-performance liquid chromatography-mass spectrometry(HPLC-MS)characterization and toxicity evaluation with the quantitative structure-activity relationship(QSAR)method suggest that TC photodegradation intermediates produced by NDBC have less aromatic structure and are less toxic than those produced by DBC.We adopted a theoretical approach to clarify the relationship between the surface groups of NDBC and the photoactive species produced.Our results add to the understanding of the photochemical behavior of NDBC.

关键词： Dissolved black carbon(DBC) N-doping Organic pollutants Band gap Photodegradation

Strategies that regulate LSD1 for novel therapeutics

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1494-1507页

作者： Meng Li Mengge Dai Bing Cheng Shaotong Li Enhui guo Junwei Fu ting Ma Bin Yu School of Pharmaceutical Sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Zhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical Sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China Pingyuan Laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiang 453007China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic modifications.Lysine-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various diseases.LSD1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic target.Several LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical stage.LSD1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or activation.While the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other factors.For example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with LSD1.Moreover,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase activity.Therefore,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.

关键词： LSD1 regulation Transcription repression Transcription activation the Corepressor complex Post-transcriptional modifications Metabolites

Translocation of a fish spike from the pharynx to the thyroid gland:A case report

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World Journal of Clinical Cases 2024年第7期12卷 1365-1370页

作者： Deng Li Wan-ting Zeng Jian-guo Jiang Ji-Chuan Chen Department of Otolaryngology Head and Neck Surgery Army Medical Center of PLAChongqing 400042China

BACKGROUND A fish spike stuck in the throat is a common ear,nose,and throat(ENT)emergency.However,it is very rare for a fish spike to reach the thyroid tissue through the throat,which is very dangerous and can lead to pharyngeal fistula,cervical abscess,mediastinal abscess,and thyroid abscess.Proper and timely management can help reduce complications,especially in elderly patients.CASE SUMMARY In the case presented here,the causative factor was dentures,but improper management aggravated the condition.In the case presented here,an elderly woman with a history of accidentally swallowing fish bones for 20 d had a sensation of foreign bodies in her throat.Eventually,computed tomography(CT)of the neck showed that the left side of the thyroid gland had a dense shadow in the form of a stripe.CONCLUSION If a fishbone foreign body is not visible during endoscopic examination but the patient has significant symptoms,the surgeon should be aware that the fishbone may be lodged in the thyroid.To avoid a misdiagnosis,ultrasound,CT,and other tests can be used to clarify the diagnosis.T The first step in treating a fish bone in the thyroid gland is to determine the position of the foreign body and the extent of the infection,and to develop a personalized surgical plan for its removal.At the same time,scientific information should be made available to the general public so that people know that if a fish bone is accidentally lodged,they should not force it to be swallowed or be spit out by inducing vomiting,which are incorrect methods and may aggravate the condition or even cause it to migrate outside the cavity,leading to serious complications,as in this reported case.

关键词： Fish spike Thyroid Pharynx Foreign body migration Case report

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

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World Journal of Hepatology 2024年第4期16卷 612-624页

作者： Long guo Peng Peng Wei-ting Peng Jie Zhao Qi-Quan Wan Department of Respiratory and Critical Care Medicine The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Clinical Laboratory Medicine Center Zhuzhou Hospital Affiliated to Xiangya School of MedicineCentral South UniversityZhuzhou 421007Hunan ProvinceChina The Second Affiliated Hospital Class Xiangya School of MedicineCentral South UniversityChangsha 410013Hunan ProvinceChina Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200127China Department of Transplant Surgery The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Engineering and Technology Research Center for Transplantation Medicine of National Health Commission The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

关键词： Liver transplantation Klebsiella pneumoniae infections Carbapenem-resistant Klebsiella pneumoniae Risk factors Outcomes