1.Preparation and characterization of a novel self-assembled polypeptide hydrogel sustainably releasing platelet-rich plasma growth factors
Fengying QI ; Lei WANG ; Dongdong LI ; Shaoduo YAN ; Kun LIU ; Yizhe ZHENG ; Zixin HE ; Xiaoyang YI ; Donggen WANG ; Qiuxia FU ; Jun LIANG
Chinese Journal of Tissue Engineering Research 2024;28(15):2364-2370
BACKGROUND:Due to the sudden release and the rapid removal by proteases,platelet-rich plasma hydrogel leads to shorter residence times of growth factors at the wound site.In recent years,researchers have focused on the use of hydrogels to encapsulate platelet-rich plasma in order to improve the deficiency of platelet-rich plasma hydrogels. OBJECTIVE:To prepare self-assembled polypeptide-platelet-rich plasma hydrogel and to explore its effects on the release of bioactive factors of platelet-rich plasma. METHODS:The self-assembled polypeptide was synthesized by the solid-phase synthesis method,and the solution was prepared by D-PBS.Hydrogels were prepared by mixing different volumes of polypeptide solutions with platelet-rich plasma and calcium chloride/thrombin solutions,so that the final mass fraction of polypeptides in the system was 0.1%,0.3%,and 0.5%,respectively.The hydrogel state was observed,and the release of growth factors in platelet-rich plasma was detected in vitro.The polypeptide self-assembly was stimulated by mixing 1%polypeptide solution with 1%human serum albumin solution,so that the final mass fraction of the polypeptide was 0.1%,0.3%,and 0.5%,respectively.The flow state of the liquid was observed,and the rheological mechanical properties of the self-assembled polypeptide were tested.The microstructure of polypeptide(mass fraction of 0.1%and 0.001%)-human serum albumin solution was observed by scanning electron microscope and transmission electron microscope. RESULTS AND CONCLUSION:(1)Hydrogels could be formed between different volumes of polypeptide solution and platelet-rich plasma.Compared with platelet-rich plasma hydrogels,0.1%and 0.3%polypeptide-platelet-rich plasma hydrogels could alleviate the sudden release of epidermal growth factor and vascular endothelial growth factor,and extend the release time to 48 hours.(2)After the addition of human serum albumin,the 0.1%polypeptide group still exhibited a flowing liquid,the 0.3%polypeptide group was semi-liquid,and the 0.5%polypeptide group stimulated self-assembly to form hydrogel.It was determined that human serum albumin in platelet-rich plasma could stimulate the self-assembly of polypeptides.With the increase of the mass fraction of the polypeptide,the higher the storage modulus of the self-assembled polypeptide,the easier it was to form glue.(3)Transmission electron microscopy exhibited that the polypeptide nanofibers were short and disordered before the addition of human serum albumin.After the addition of human serum albumin,the polypeptide nanofibers became significantly longer and cross-linked into bundles,forming a dense fiber network structure.Under a scanning electron microscope,the polypeptides displayed a disordered lamellar structure before adding human serum albumin.After the addition of human serum albumin,the polypeptides self-assembled into cross-linked and densely arranged porous structures.(4)In conclusion,the novel polypeptide can self-assemble triggered by platelet-rich plasma and the self-assembly effect can be accurately adjusted according to the ratio of human serum albumin to polypeptide.This polypeptide has a sustained release effect on the growth factors of platelet-rich plasma,which can be used as a new biomaterial for tissue repair.
2.Clinical characteristics analysis of primary pancreatic lymphoma
Yinghao SUN ; Jianing LI ; Kun HE ; Liang ZHU ; Yunlu FENG ; Qiang WANG ; Qingwei JIANG ; Yan ZHANG ; Qiang XU ; Zheng WANG ; Jingya ZHOU ; Dong WU
Chinese Journal of Pancreatology 2024;24(1):52-56
Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.
3.Laparoscopic surgery for high-risk prostate cancer:urinary and oncologic outcomes of vesicourethral anastomosis with maximal urethral length and bladder neck preservation
Kun ZHENG ; Xiaoyong HU ; Qiang FU ; Wang LI ; Ying WANG ; Nailong CAO ; Jiasheng CHEN ; Ranxing YANG
Journal of Modern Urology 2024;29(7):612-616
Objective To explore the application value of vesicourethral anastomosis with maximal urethral length preservation(MULP)and bladder neck preservation(BNP)in laparoscopic radical prostatectomy(LRP)or robot-assisted laparoscopic radical prostatectomy(RALP)for high-risk prostate cancer(HRPC)in terms of early urinary continence and oncology.Methods Clinical data of 23 HRPC patients who underwent LRP(including RALP)with MULP and BNP in our hospital during May 2022 and Jan.2024 were retrospectively analyzed.Patients'basic information,surgical parameters,postoperative complications,oncological outcomes and urinary incontinence were collected and analyzed.Results All operations were completed successfully without conversion to open surgery.The operation time was(108±31)min,average blood loss(112±45)mL,hospital stay(5.5±1.5)days,urethral catheterization time(12.6±1.8)days,and no patient received blood transfusion during operation.The urinary continence rates at the time of catheter removal,and at 1,3,and 6 months after surgery were 39.1%,65.2%,73.9%,and 91.3%,respectively.Two patients had positive margins,both of which were at the neurovascular bundle.No patient developed surgery-related complications,urinary obstruction or fistula after surgery.Conclusion Vesicourethral anastomosis with MULP and BNP in LRP for HRPC can effectively improve patients'early urinary continence rate and postoperative quality of life without increasing the oncological risk.
4.Research status of pharmacological mechanism of PCSK9 inhibitors and discussion of their clinical application
Wen-Hui MO ; Si-Lei XU ; Xia HE ; Niu-Niu BAI ; Meng-Ying YUAN ; Zhi-Min LI ; Jiao ZHANG ; Fei WANG ; Yuan-Kun ZHENG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2438-2441
Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.
5.Clinical trial of irinotecan combined with capecitabine and bevacizumab in the treatment of colorectal cancer patients with liver metastases
Wei WANG ; Jin-Kun CHENG ; Zheng-Dao YANG
The Chinese Journal of Clinical Pharmacology 2024;40(18):2660-2664
Objective To explore the efficacy of oxaliplatin and irinotecan combined with capecitabine and bevacizumab on disease control rate,serum vascular endothelial growth factor(VEGF)and carbohydrate antigen 199(CA199)in colorectal cancer(CRC)combined with liver metastases.Methods CRC patients with liver metastases and elevated CA199 were divided into control group and treatment group.The control group was given irinotecan hydrochloride injection(150 mg·m-2,iv infusion,D1)combined with capecitabine tablets(1 000 mg·m-2,oral,bid,D 1-D 14)and bevacizumab injection(7.5 mg·m-2,iv infusion,D1).The treatment group was given oxaliplatin injection(130 mg·m-2,iv infusion,D 1)combined with capecitabine tablets(1 000 mg·m-2,oral,bid,D 1-D 14)and bevacizumab injection(7.5 mg·m-2,iv infusion,D 1).All were treated for 4 cycles(21 d/cycle).The total response rate,disease control rate,progression-free survival(PFS),survival rate at 1 year after treatment,serum VEGF,CA199,and the occurrence of toxic and the safety were evaluated.Results The treatment group and the control group were included in 46 and 52 cases,respectively.Total response rates in treatment group and control group were 17.31%(9 cases/52 cases)13.04%(6 cases/46 cases),disease control rates were 59.62%(31 cases/52 cases)and 50.00%(23 cases/46 cases),the difference was not statistically significant(all P>0.05).The median PFS in treatment group and control group at 1 year after treatment were 8.50 and 10.50 months;progression-free survival rate were 42.31%(22 cases/52 cases)and 30.43%(14 cases/46 cases);overall survival rates were 73.08%(38 cases/52 cases)and 67.39%(31 cases/46 cases),the difference was not statistically significant(all P>0.05).After treatment,levels of serum VEGF in treatment group and control group were(442.59±67.90)and(518.56±82.08)pg·mL-1,CA199 levels were(73.85±13.66)and(92.28±16.17)U·mL-1,the difference were statistically significant(all P<0.05).During treatment,the incidence of grade Ⅲ~Ⅳ diarrhea in oxaliplatin group and irinotecan group were 1.92%(1 case/52 cases)and 17.39%(8 cases/46 cases),respectively,the incidence of neutropenia were 15.38%(8 cases/52 cases)and 36.96%(17 cases/46 cases),respectively,the differences were statistically significant(all P<0.05).There were no significant differences in nausea,vomiting,thrombocytopenia,anemia,peripheral neuropathy,hand-foot syndrome and alopecia between 2 groups(all P>0.05).Conclusion Oxaliplatin and irinotecan respectively combined with capecitabine and bevacizumab have similar clinical curative effect and survival at 1 year after treatment in patients with CRC and liver metastasis.However,oxaliplatin and capecitabine combined with bevacizumab can significantly reduce serum VEGF,CA199 levels with higher safety.
6.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
Objective:
This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines.
Methods:
Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud.
Results:
In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model.
Conclusion
In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.
7.The pedicle isthmus angle: a new imaging parameter for lumbar spondylolysis in young male patients
Fuxin WANG ; Kun WANG ; Zheng ZHANG ; Zhaohu MAO ; Ruoxian SONG
Chinese Journal of Orthopaedics 2024;44(18):1207-1214
Objective:To introduce a novel risk factor for lumbar spondylolysis, the pedicle isthmus angle (PIA), and to explore its underlying mechanism and clinical relevance.Methods:A retrospective analysis of CT imaging data from young male patients with lumbar spondylolysis, admitted to the 960th Hospital of the Joint Logistic Support Force of the PLA between January 2018 and August 2023, was conducted. The study included 119 cases of unilateral spondylolysis and 339 cases of bilateral spondylolysis, with a mean age of 22.8±3.4 years (range 18-30 years). A control group of 458 patients with normal lumbar CT scans, presenting with low back pain, was also analyzed. Their mean age was 22.9±3.5 years (range 18-30 years). The PIA of the left and right sides of the L 3, L 4, and L 5 vertebrae in both the spondylolysis and control groups were measured using CT imaging. Differences in PIA measurements between the left and right sides, as well as between groups, were compared. Binary logistic regression analysis identified risk factors for lumbar spondylolysis. The receiver operating characteristic (ROC) curve and Youden index were used to determine the critical risk threshold for lumbar spondylolysis. Results:No significant differences were found between the spondylolysis and control groups in terms of gender, age, height, weight, or body mass index (BMI) ( P>0.05). Similarly, there was no significant difference in the left and right PIA measurements for the L 3, L 4, and L 5 vertebrae in either group ( P>0.05). The PIA of the L 3 and L 4 vertebrae was not significantly different between the groups (107.2°±3.5° vs. 107.1°±3.5°, t=0.270, P=0.787; 110.6°±3.5° vs. 110.5°±4.0°, t=0.441, P=0.659). However, the PIA of the L 5 vertebra was significantly larger in the spondylolysis group (117.7°±4.7°) compared to the control group (114.0°±4.9°) ( t=11.654, P<0.001). Logistic regression analysis identified an increased PIA at L 5 ( β=0.159, OR=1.172, P<0.001) as a risk factor for lumbar spondylolysis. According to the ROC curve and Youden index, the risk of lumbar spondylolysis increased substantially when the L 5 PIA exceeded 115.8°. The area under the curve (AUC) was 0.709, with a sensitivity of 0.670 and a specificity of 0.644. Conclusion:PIA is an objective and effective imaging parameter for predicting lumbar spondylolysis. It aids in understanding the pathophysiology of spondylolysis, identifying high-risk individuals, and informing prevention and treatment strategies for lumbar spondylolysis.
8.The application of mobile blood glucose management in pregnant women with gestational diabetes:a scoping review
Qiaosong WANG ; Kun ZHANG ; Xueling ZHANG ; Qirong ZHENG ; Jingping YANG ; Jingjing LIN ; Rongjin LIN
Chinese Journal of Nursing 2024;59(10):1270-1277
Objective A scoping review of research on mobile glucose management in pregnant women with gestational diabetes mellitus was conducted to provide references for clinical providers to conduct mobile glucose management and related research.Methods Based on Arksey and O'Malley's scoping review reporting framework,JBI Library,Cochrane Library,PubMed,Web of Science,Embase,CINAHL Complete,CBM,China National Knowledge In-frastructure(CNKI),and Wanfang Database were retrieved.The search time frame was from the establishment of the databases to February 14,2023.The included literature was screened,summarized and analyzed.Results A total of 65 publications from 11 countries were included,among which 38 were randomized controlled trials,27 were experimental studies.The vehicles relied on for mobile glucose management in gestational diabetes mainly included APPs,remote monitoring systems,professional websites,and social platforms,which could provide health education,glucose management monitoring and recording,social support,and glucose management follow-up and reminders to pregnant women.Most of the studies focus on the glucose index and drug use,pregnancy outcome,self-management,quality of life,user experience and resource cost of pregnant women.Conclusion Mobile glucose management carriers are geographically specific and have a positive effect on glucose control in gestational diabetes.Future studies need to further develop localized mobile glucose management intervention protocols and conduct more high-quality randomized controlled studies to verify their effectiveness.
9.Factors for low libido in male patients with sexual dysfunction
Qiu-Chen LÜ ; Rui WANG ; Zu-Long WANG ; Tian-Ji ZHANG ; Tao ZHENG ; Kun-Long LÜ ; Yong-Hao NAN
National Journal of Andrology 2024;30(8):734-737
Objective:To analyze the factors for low libido in male patients with sexual dysfunction and provide some evidence for the clinical diagnosis and treatment of the condition.Methods:We retrospectively analyzed the clinical data on 111 cases of sex-ual dysfunction(including disorders in erection,ejaculation or libido)treated in the Zhengzhou University First Hospital from June to September 2023.According to the patients'complaints of low libido or accompanied symptoms,we divided them into a normal libido group(n=68)and a low libido(n=43),obtained their scores on IIEF-5,Premature Ejaculation Diagnostic Tool(PEDT),13-1-tem Self-Rating Libido Scale for Males(SRLS-M),Patients'Health Questionnaire-9(PHQ-9)and General Anxiety Disorder-7(GAD-7),examined the levels of the sexual hormones FSH,LH,PRL,T,free testosterone(fT),E2,?insulin-like growth factor 1(IGF-1)and growth hormone(GH),compared the basic parameters between the two groups,and analyzed their correlation with the libido values.Results:The IIEF-5,PEDT and libido scores and IGF-1 level were significantly higher and the GAD-7 score remark-ably lower in the normal than in the low libido group(P<0.05),but no statistically significant differences were observed between the two groups in the PHQ-9 score and the levels FSH,LH,PRL,T,fT,E2,T/E2 and GH(P>0.05).The libido value was correla-ted positively with the I1EF-5(r=0.28,P<0.01)and PEDT scores(r=0.29,P<0.01)and IGF-1 level(r=0.23,P<0.05),but negatively with the GAD-7 score(r=-0.21,P<0.05).Conclusion:Low libido results from multiple factors,which cannot be fully explained by sexual hormone levels but is closely related to the decreased level of IGF-1 and severity of ED and anxiety.
10.Overexpression of mitoNEET inhibits ferroptosis-induced mitochondrial metabolic dysfunction in brown adipocytes
Hongyu ZHENG ; Zhen TIAN ; Yanxia WANG ; Kun ZHOU ; Zhong REN ; Zhixiang ZHOU ; Wenhao XIONG ; He ZHENG ; Zhisheng JIANG
Chinese Journal of Pathophysiology 2024;40(5):852-861
AIM:To investigate the potential impact of mitoNEET[mitochondrial protein containing Asn-Glu-Glu-Thr(NEET)sequence]on mitochondrial metabolism in brown adipocytes,and to elucidate its underlying mecha-nism.METHODS:An in vitro model of primary mouse brown adipocytes was established.Western blot were utilized to detect relevant proteins,and iron ion and ATP content was measured using kits.Mitochondrial membrane potential and re-active oxygen species(ROS)were assessed by fluorescence microscopy and flow cytometry.RESULTS:The expression of the ferroptosis-related protein ACSL4 increased by 1.13 times in ferroptosis inducer erastin treatment group,whereas the expression of SLC7A11 and GPX4 decreased by 27.33%and 25.33%,respectively,compared with control group(P<0.05).The expression of Nrf1,PGC-1α,MFN2 and UCP1 proteins,related to mitochondrial energy metabolism,de-creased by 20.98%,15.17%,15.03%and 34.22%,respectively(P<0.05).Additionally,the mitoNEET protein con-tent was significantly reduced by 42.14%(P<0.05).The iron ion content in erastin group was substantially increased by 1.80 times compared with control group.However,a notable decrease in ATP content of 14.95%was seen(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated a significant decrease in the mitochon-drial membrane potential of brown adipocytes in erastin group,with reductions of 52.18%and 61.31%(P<0.05),re-spectively.A substantial increase in mitochondrial ROS content of 80.97%was seen(P<0.05).Western blot analysis of overexpressed stable strains revealed a significant elevation in mitoNEET levels in brown adipocytes following lentivirus transfection,exhibiting an increase of 11.19 times(P<0.05),thus confirming successful transfection.The LV-mitoNEET group exhibited a significant decrease of 37.95%in the expression of ferroptosis-related protein ACSL4 in brown adipose cells compared with control group.Additionally,there was a notable increase of 77.82%and 66.3%in the expression of SLC7A11 and GPX4,respectively(P<0.05).Up-regulation was observed in the expression of MFN2(79.06%),PGC-1α(72.89%),Nrf1(40.14%),and UCP1(31.68%)(P<0.05).The test results demonstrated that the LV-mitoNEET group experienced a reduction of 43.5%in iron ion content compared with control group while exhibiting an increase of 33.5%in ATP content(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated that mitoNEET overexpression led to a significant increase in the mitochondrial membrane potential of erastin-induced brown adipocytes,with increments of 17.61%and 96.05%,respectively.Additionally,mitoNEET overexpression effec-tively reduced the production of mitochondrial ROS by 24.48%(P<0.05).CONCLUSION:Our findings suggest that mitoNEET overexpression can effectively inhibit the disruption of mitochondrial energy metabolism caused by ferroptosis-induced death of brown adipocytes.

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