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Identifying and validating MMP family members(MMP2,MMP9,MMP12,and MMP16)as therapeutic targets and biomarkers in kidney renal clear cell carcinoma(KIRC)

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Oncology Research 2024年第4期32卷 737-752页

作者： KUNLUN LI DANDAN LI BARBOD HAFEZ MOUNIR M.SALEM BEKHIT YOUSEF A.BIN JARDAN FARS KAED ALANAZI EHAB I.TAHA SAYED H.AUDA FAIQAH RAMZAN MUHAMMAD JAMIL The Second Affiliated hospital of Harbin Medical University Harbin Medical UniversityHarbinChina Department of Pharmaceutical Engineering Jiangsu Ocean UniversityLianyungangChina Department of Biological Engineering University of SalfordSalfordUK Department of Pharmaceutics College of PharmacyKing Saud UniversityRiyadhSaudi Arabia Department of Animal and Poultry Production Faculty of Veterinary and Animal SciencesGomal UniversityDera Ismail KhanPakistan Department of Arid Zone Research PARC instituteDera Ismail KhanPakistan

Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and mortality.The MMP family assumes a crucial role in tumor invasion and metastasis.This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma(KIRC)through a comprehensive approach encompassing both computational and molecular analyses.STRING,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,ENCORI,DrugBank,targeted bisulfite sequencing(bisulfite-seq),conventional PCR,Sanger sequencing,and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC.By performing STRING and Cytohubba analyses of the 24 MMP gene family members,MMP2(matrix metallopeptidase 2),MMP9(matrix metallopeptidase 9),MMP12(matrix metallopeptidase 12),and MMP16(matrix metallopeptidase 16)genes were denoted as hub genes having highest degree scores.After analyzing MMP2,MMP9,MMP12,and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines,interestingly,all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls.The notable effect of the up-regulated MMP2,MMP9,MMP12,and MMP16 was also documented on the overall survival(OS)of the KIRC patients.Moreover,targeted bisulfite-sequencing(bisulfite-seq)analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes(MMP2,MMP9,MMP12,and MMP16).In addition to this,hub genes were involved in various diverse oncogenic pathways.The MMP gene family members(MMP2,MMP9,MMP12,and MMP16)may serve as therapeutic targets and prognostic biomarkers in KIRC.

关键词： KIRC MMP gene family Chemotherapy Overall survival

Congenital absence of the lateral meniscus:A case report

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World Journal of Orthopedics 2024年第5期15卷 477-482页

作者： Hamad Ali Alkhunayfir Abdulaziz Ali AlQahtani Abdulrahman Jalwi Korkoman Department of Orthopedic Surgery Prince Muhammed bin Abdulaziz HospitalRiyadh 61422Saudi Arabia Department of Orthopedic Surgery Prince Sultan Military Medical CityRiyadh 12233Saudi Arabia Department of Orthopedic Surgery University of BishaBisha 67714Saudi Arabia

BACKGROUND Congenital absence of the menisci is a rare anatomical variation characterized by the absence or underdevelopment of one or both menisci in the knee joint.The menisci are crucial in load distribution,joint stability,and shock absorption.Understanding the clinical presentation,diagnosis,and management of this condition is important for optimal patient care.CASE SUMMARY A 27-year-old male with a long-standing history of knee pain underwent diagnostic arthroscopy,revealing a congenital absence of the meniscus.The patient's clinical findings,imaging results,surgical procedures,and pertinent images are detailed.This case presents a unique aspect with the congenital absence of the meniscus,contributing valuable insights to the literature on rare anatomical anomalies.CONCLUSION This case of congenital absence of the menisci highlights the diagnostic challenges posed by rare anomalies.The diagnostic arthroscopy played a crucial role in identifying the absence of the meniscus and providing an explanation for the patient's persistent knee pain.The case underscores the importance of individualized treatment approaches,including physical therapy,for optimal management of rare meniscal anomalies.Further research is warranted to explore effective management strategies for the aforementioned cases and to expand our knowledge of these rare conditions.

关键词： Lateral meniscus Arthroscopy Knee joint Menisci reformation Magnetic resonance imaging Case report

Delayed Grafting as a Valid Technique in Burn Management: Experience from a Burn Unit in Oman

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Modern Plastic Surgery 2024年第1期14卷 9-14页

作者： Taif Alsafy Joe Jacob Anish Thadathil Elias Ahmed Salah El Din Salim Mohammed Ghawas Majid Tariq Saud Albusaidi Ahmed Al Jabri Al Anood Al Hadhrami Mutazz Obeid Al Khaldi Moath Abdelhamid Shummo Karim Mohamed Haridi Aml Eid Saleh Said Al-Busaidi Department of Plastic and Reconstructive Surgery Sultan Qaboos Hospital Salalah Oman ENT Department Al Nahdha Hospital Muscat Oman Department of Plastic Reconstructive and Craniofacial Surgery Khoula Hospital Muscat Oman

Background: Early excision and grafting has been the preferred method of managing major burns around the world since 1970. Considering the advances in health care and the development of new antibiotics over the past 50 years, delayed grafting as a technique for the management of burns over 15%-20% of total body surface area (TBSA) could have comparable results to that of early excision. This study aims to highlight the outcomes of practicing delayed grafting in burn patients. Methods: A case series analysis was performed of 51 patients who were admitted to the burns unit in sultan Qaboos hospital Salalah with over 20% TBSA between January 2014 and December 2019. The patients received prophylactic antibiotics and silver sulphadiazine dressing until the burn eschar had completely separated, followed by grafting. Results: Two patients were lost during the entire duration of the study. The mortality rate was comparable to that of early excision, while the rate of hypertrophic scarring was lower than the range reported by other studies. Conclusion: In the management of patients with over 20% TBSA, delayed grafting after complete separation of eschar is still a valid technique.

关键词： Burns Burn Units Burn Management Delayed Grafting Major Burns Treatment Efficacy

Knowledge, Attitude, and Practice of Using Helmets in Children amongst Parents to Prevent Head Injuries: A Cross-Sectional Study in Riyadh, Saudi Arabia

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Open Journal of Pediatrics 2024年第2期14卷 255-265页

作者： Turki Salah Aldeen Bukhari Abdullah Yahya Aldhban Anas Abdulrahman Alqasem Dona Jamal Al Hatlani Hareth Aldosaimani Hamad A. Al Madi Khalid Alqahtani Prince sultan Military Medical City Riyadh Saudi Arabia Emergency Department Disaster Medicine and Emergency Preparedness Prince Sultan Military Medical City Riyadh Saudi Arabia Emergency Department Asir Central Hospital Abha Saudi Arabia

Objectives: The primary objective was to characterize the range of Knowledge, Attitude, and Practice (KAP) of Helmet use in children amongst parents to prevent head injuries and death. Methods: This is a cross-sectional study, done by online survey using a snowball sampling technique, the number of included responses were 386 parents (Male and female) living in Riyadh Aged 21 - 60 years old or above. Results: The study showed that there is a difference in Parents’ belief in the importance of helmet use while riding a Bicycle vs Motorcycle/Quad bike and that was affected by parents’ education level, almost all the people who answered the survey (76.7%) agree that it is important for their children to wear a helmet when riding both a Bicycle and a Motorcycle or Quadbike with a cumulative percentage of (93.8%). And almost all agreed on multiple approaches to help increase helmet use be it by forcing rental shops to give out helmets, forcing sellers to recommend the use of helmets, increasing awareness campaigns, and imposing fines for not wearing helmets. Conclusions: This study is the first to explore Family helmet use while riding Bicycles and Motorcycles/Quad bikes. Although Parent’s belief in the importance of helmet use for their children was high, it is clear that the level of practice is low. With that the risk of head injuries might be high, our findings suggest that safety interventions for increasing pediatric helmet use are needed to increase helmet use and reduce the risk of head injury and hospitalization.

关键词： Head Trauma Head Injury Helmet Bicycle Motorcycle Quad Bike KAP Knowledge Attitude Practice

Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

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World Journal of Clinical Cases 2024年第9期12卷 1585-1596页

作者： Osman Boyalı Serdar Kabatas ErdinçCivelek Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Turkey Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34360Turkey Department of Physical Medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Turkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell) Liv HospitalIstanbul 34340Turkey Department of Histology and Embryology Istinye UniversityFaculty of Medicineİstanbul 34010Turkey Center for Stem Cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Turkey

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and patients are affected for the rest of their lives.Currently,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal spasticity.However,none of these methods can provide full symptom relief.This has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and safety.AIM To analyze the efficacy and safety of MSCT in CP patients.METHODS Our sample consists of four CP patients who cannot stand or walk without external support.All of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)instruments.We utilized the Modified Ashworth Scale(MAS)to measure spasticity.RESULTS We found significant improvements in MAS scores after the intervention on both sides.Two months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046.However,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity,and it partially improves motor functions.

关键词： Cerebral palsy Mesenchymal stem cell Transplantation Wharton’s jelly Muscle spasticity

Occurrence of K1 and K2 serotypes and genotypic characteristics of extended spectrumβ-lactamases-producing Klebsiella pneumoniae isolated from selected hospitals in Malaysia

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Asian Pacific Journal of Tropical Medicine 2024年第1期17卷 30-38页

作者： Nurul Syazrah Anuar Hazmin Hazman Sharven Raj Jeyakumar Mohd Nasir Mohd Desa Hasni Idayu Saidi Siti Norbaya Masri Nur Afiza Aziz Nurshahira Sulaiman Department of Biomedical Science Faculty of Medicine and Health SciencesUniversiti Putra Malaysia43400UPM SerdangSelangorMalaysia Department of Medical Microbiology Faculty of Medicine and Health SciencesUniversiti Putra Malaysia43400UPM SerdangSelangorMalaysia Microbiology Unit Department of PathologyHospital Sultanah AminahJalan Persiaran Sultan Abu Bakar80100 Johor BahruJohorMalaysia

Objective:To determine the distribution,phenotypic and genetic background of extended spectrumβ-lactamases(ESBL)-producing Klebsiella(K.)pneumoniae clinical isolates associated with K1 and K2 serotypes in two selected hospitals in Malaysia.Methods:A total of 192 K.pneumoniae isolates were collected and subjected to antibiotic susceptibility,hypermucoviscosity test and multiplex PCR to detect the presence of K1-and K2-serotype associated genes.Multilocus sequence typing(MLST)was performed on ESBL-producing K.pneumoniae isolates presented with K1 and K2 serotypes,followed by phylogenetic analysis.Results:A total of 87 out of 192(45.3%)of the K.pneumoniae isolates collected were ESBL producers.However,only 8.3%(16/192)and 10.9%(21/192)of the total isolates were detected to carry K1-and K2-serotype associated genes,respectively.Statistical analysis showed that K1 and K2 capsular serotypes were not significantly associated with ESBL phenotype(P=0.196).However,they were significantly associated with hypervirulent,as demonstrated by the positive string test(P<0.001).MLST analysis revealed that ST23 as the predominant sequence type(ST)in the K1 serotype,while the ST in the K2 serotype is more diverse.Conclusions:Although the occurrence of ESBL-producing isolates among the hypervirulent strains was low,their coexistence warrants the need for continuous surveillance.MLST showed that these isolates were genetically heterogeneous.

关键词： Extended spectrumβ-lactamases Klebsiella pneumoniae Capsular serotypes Genotypic

Assistive techniques and their added value for tremor classification in multiple sclerosis

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Neural Regeneration Research 2024年第5期19卷 977-978页

作者： Nabin Koirala Abdulnasir Hossen Ioannis U.Isaias Jens Volkmann Muthuraman Muthuraman Child Study Center School of MedicineYale UniversityNew HavenCTUSA Department of Electrical&Computer Engineering Sultan Qaboos UniversityAl-KhodMuscatOman Neural Engineering with Signal Analytics and Artificial Intelligence Department of NeurologyUniversity Hospital of WürzburgWürzburgGermany Centro Parkinson e Parkinsonism Azienda Socio Sanitaria Territoriale G.Pini-CTO20126 MilanItaly

Tremor occurs in about half of multiple sclerosis(MS)patients.MS tremor has a broad frequency range of 2.5-7 Hz,with a higher prevalence of postural tremor(44%)compared to intentional tremor(6%)(Alusi et al.,2001).Tremor may affect the upper and lower extremities,head,and trunk,and may even affect the vocal cords in isolated cases of palatal tremor.MS tremor is classically attributed to lesions of the brain stem,cerebellum,or cerebellar peduncles,and tremor intensity has been shown to correlate with the number of lesions or their functional connections.However,recent work has demonstrated that inflammatory damage to the cerebello-thalamic and cortico-thalamic pathways might also play an important role in causing tremor,as it co-occurs with other signs and symptoms of MS such as dysarthria,dysmetria,dysdiadochokinesia,and dystonia(Alusi et al.,2001).

关键词： tremor sclerosis

Safety and efficiency of Wharton’s Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury:First results of a phase I study

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World Journal of Stem Cells 2024年第6期16卷 641-655页

作者： Serdar Kabatas ErdinçCivelek Osman Boyalı Gülseli Berivan Sezen Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Türkiye Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye Department of Neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of Physical Medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Türkiye Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Türkiye Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Türkiye Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell) Liv HospitalIstanbul 34340Türkiye Department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye Center for Stem Cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Traumatic brain injury(TBI)is characterized by a disruption in the normal function of the brain due to an injury following a trauma,which can potentially cause severe physical,cognitive,and emotional impairment.Stem cell transplantation has evolved as a novel treatment modality in the management of TBI,as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain.Wharton’s Jelly-derived mesenchymal stem cells(WJ-MSCs)have recently shown beneficial effects in the functional recovery of neurological deficits.AIM To evaluate the safety and efficiency of MSC therapy in TBI.METHODS We present 6 patients,4 male and 2 female aged between 21 and 27 years who suffered a TBI.These 6 patients underwent 6 doses of intrathecal,intramuscular(i.m.)and intravenous transplantation of WJ-MSCs at a target dose of 1×106/kg for each application route.Spasticity was assessed using the Modified Ashworth scale(MAS),motor function according to the Medical Research Council Muscle Strength Scale,quality of life was assessed by the Functional Independence Measure(FIM)scale and Karnofsky Performance Status scale.RESULTS Our patients showed only early,transient complications,such as subfebrile fever,mild headache,and muscle pain due to i.***.injection,which resolved within 24 h.During the one year follow-up,no other safety issues or adverse events were reported.These 6 patients showed improvements in their cognitive abilities,muscle spasticity,muscle strength,performance scores and fine motor skills when compared before and after the intervention.MAS values,which we used to assess spasticity,were observed to statistically significantly decrease for both left and right sides(P<0.001).The FIM scale includes both motor scores(P<0.05)and cognitive scores(P<0.001)and showed a significant increase in pretest posttest analyses.The difference observed in the participants’Karnofsky Performance Scale values pre and post the intervention was statistically significant(P<0.001).CONCLUSION This study showed

关键词： Traumatic brain injury Wharton Jelly Stem cell therapy Transplantation Mesenchymal stem cell

Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma

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Chinese Journal of Cancer Research 2024年第2期36卷 195-214页

作者： Sana Rashid Yingchuan Sun Umair Ali Khan Saddozai Sikandar Hayyat Muhammad Usman Munir Muhammad Usman Akbar Muhammad Babar Khawar Zhiguang Ren Xinying Ji Malik Ihsan Ullah Khan Institute of Molecular Biology and Biotechnology University of LahoreLahore 54590Pakistan Department of Internal Oncology(Section Ⅰ) Xuchang Municipal Central HospitalXuchang 461000China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Australian Institute for Bioengineering&Nanotechnology the University of QueenslandBrisbane 4072Australia Gomal Center of Biochemistry and Biotechnology Gomal UniversityDera Ismail Khan 29111Pakistan Applied Molecular Biology and Biomedicine Lab Department of ZoologyUniversity of NarowalNarowal Punjab 51600Pakistan Kaifeng Municipal Key Laboratory for Infection and Biosafety Henan International Joint Laboratory of Nuclear Protein RegulationSchool of Basic Medical SciencesHenan UniversityKaifeng 475004China Faculty of Basic Medical Subjects Shu-Qing Medical College of ZhengzhouZhengzhou 450064China Department of Medicine Huaxian County People's HospitalHuaxian 456400China

Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

关键词： Hepatocellular carcinoma circulating tumor DNA biomarkers single nucleotide variations diagnosis prognosis