1.Research progress on natural active ingredients intervening in the hypoxia-pyroptosis-inflammation cascade in intervertebral disc degeneration through HIF-1α
Hao WANG ; Renchang CHEN ; Wenhao HUANG ; Bingqian ZHOU ; Xiqiu ZHENG ; Jiahao WANG ; Nianhu LI ; Yadong WU
China Pharmacy 2026;37(8):1092-1098
Intervertebral disc degeneration (IVDD) is the core cause of chronic low back pain, which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α (HIF-1α) is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine (TCM) have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects, favorable efficacy, and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein, curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression: targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade, inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals, intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity, and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.
2.Retrospective study on the impact of penile corpus cavernosum injection test on pe-nile vascular function
Yan CHEN ; Kuangmeng LI ; Kai HONG ; Shudong ZHANG ; Jianxing CHENG ; Zhongjie ZHENG ; Wenhao TANG ; Lianming ZHAO ; Haitao ZHANG ; Hui JIANG ; Haocheng LIN
Journal of Peking University(Health Sciences) 2024;56(4):680-686
Objective:To investigate the impact of age,various hormonal levels,and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction(ED).Me-thods:A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography(CDDU)and intracavernosal injection test(ICI)at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023.Data were managed and processed using SPSS 29.0,and a multivariable Logistic regression analysis was conducted.Results:A total of 700 ED patients were included,with 380 showing negative ICI results and 320 positive.In the study,84 patients had a peak systolic velocity(PSV)<25 cm/s,while 616 had PSV ≥ 25 cm/s;202 patients had end-diastolic velocity(EDV)>5 cm/s,and 498 had EDV ≤5 cm/s.264 patients had ab-normal PSV and/or EDV results,and 436 had normal results for both.Patients with vascular ED had sig-nificantly lower estrogen levels(t=-3.546,P<0.001),lower testosterone levels(t=-2.089,P=0.037),and a higher rate of hyperglycemia(x2=12.772,P=0.002)compared with those with non-vascular ED.The patients with arterial ED were older(t=3.953,P<0.001),had a higher rate of hyperglycemia(x2=9.518,P=0.009),and a higher estrogen/testosterone ratio(t=2.330,P=0.020)compared with those with non-arterial ED.The patients with mixed arteriovenous ED had higher age(t=3.567,P<0.001),lower testosterone levels(t=-2.288,P=0.022),a higher rate of hyperglycemia(x2=12.877,P=0.002),and a larger estrogen/testosterone ratio(t=2.096,P=0.037)compared with those with normal findings.Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED(OR=1.009,95%CI:1.004-1.014),and glucose 7.0 mmol/L was a risk factor(OR=0.381,95%CI:0.219-0.661).Older age was a risk factor for arte-rial ED(OR=0.960,95%CI:0.938-0.982).Additionally,older age(OR=0.976,95%CI:0.958-0.993)and glucose levels of 5.6-6.9 mmol/L(OR=0.591,95%CI:0.399-0.876)were also risk fac-tors for mixed arterio-venous ED.Conclusion:Hyperglycemia and aging may impair penile cavernous body vascular function,while higher levels of estrogen may have a protective effect on it.
3.Clinical study on Da Vinci Robot-assisted prostate cancer radical operation with maximal preservation of periprostatic structures
Wenhao XU ; Liang LIU ; Min DENG ; Jingzhen ZHU ; Siyue LI ; Yu CHEN ; Qingjian WU ; Ji ZHENG
Chongqing Medicine 2024;53(18):2776-2780
Objective To observe the functional recovery situation after prostate cancer radical opera-tion with maximal preservation of the periprostatic structures (MS-RARP).Methods Sixty-seven patients with localized prostatic cancer undergoing MS-RARP in the Second Affiliated Hospital of Army Military Med-ical University from June 2019 to June 2022 were selected as the study subjects.The changes of urinary con-trol function,erection function,quality of life and total prostate specific antigen (t-PSA) were compared at the time between before operation and postoperative 6 weeks,3 months,6 months,12 months.The expanded pros-tate cancer index composite index (EPIC-50) was used to evaluate the urinary control function,the interna-tional index of erectile function (IIEF-5) questionnaire was used to evaluate the erection function of the pa-tients,and EPIC-50 and the american urological associated symptom score rating scale (AUA-SS) were used to evaluate the life satisfaction of the patients.Results The urinary control function recovery rate,erection function recovery rate and life quality satisfaction rate in postoperative 6 weeks,3 months,6 months,12 months were 71.8%,95.5%,97.3% and 98.1%;31.7%,38.1%,41.3% and 44.4%;38.9%,83.6%,88.1% and 97.0%,respectively.The median t-PSA was gradually decreased,which were 0.026(0.010,0.410),0.009 (0.003,0.060),0.006(0.001,0.050)and 0.004(0.001,0.006)ng/mL,respectively.The life quality satisfac-tion rates at various postoperative time points were significantly increased when compared with before opera-tion (P<0.05).t-PSA was significantly decreased compared with before operation (P<0.05).Conclusion RARP could protect the postoperative urinary function and sexual function,and increase the postoperative life quality of the patients.
4.The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats
Zheng WENHAO ; Lu XIAOFENG ; Chen GUANGJIN ; Shen YUFENG ; Huang XIAOFEI ; Peng JINFENG ; Wang JIAJIA ; Yin YING ; Song WENCHENG ; Xie MENGRU ; Yu SHAOLING ; Chen LILI
International Journal of Oral Science 2024;16(2):322-332
The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.
5.Clinical manifestation, muscular imaging and pathological characteristics of anti-signal recognition particle positive immune-mediated necrotizing myopathy
Shiyao LI ; Qianqian QU ; Xianzhao ZHENG ; Xiaoli MA ; Wenhao CUI ; Dan LI ; Zheng LYU ; Jiongbo ZHAO ; Jiaxuan WANG ; Cong HU ; Haidong LYU
Chinese Journal of Neurology 2024;57(9):1000-1008
Objective:To analyze the clinical characteristics, muscle imaging and pathological features of patients with anti-signal recognition particle positive immune-mediated necrotizing myopathy (SRP-IMNM).Methods:Nine patients with SRP-IMNM were collected in the Neuromuscular Disease Center of Jiaozuo People′s Hospital from May 2018 to May 2023, who were confirmed by skeletal muscle pathology and myositis-specific autoantibodies detection, and their clinical manifestations, muscle imaging and muscle pathology characteristics were systematically summarized.Results:Among the 9 patients with SRP-IMNM, there were 7 females and 2 males. The age of onset ranged from 18 to 59 years. All the patients presented proximal muscle weakness. Seven patients experienced neck weakness, and dysphagia was present in 5 patients. Laboratory examinations showed elevated serum creatine kinase levels in all 9 patients (1 866-6 725 U/L). Eight patients were combined with other antibodies positivity, except for anti-SRP antibody. Among them, 7 patients were combined with anti-Ro-52 antibody positivity, 4 patients combined with anti-Ro-52 antibody positivity alone, and 3 patients combined with 3 or more positive antibodies simultaneously. Those patients who presented with interstitial lung disease and cardiac involvement were all combined with other antibodies positivity. Seven patients completed thigh muscle magnetic resonance imaging (MRI), which showed diffuse skeletal muscle oedema, partial muscle atrophy and fatty replacement, primarily affecting the posterior thigh muscle group. Two patients underwent shank muscle MRI. The soleus involvement was evident, while the tibialis anterior muscle and gastrocnemius muscles were involved in 1 patient. All 9 patients showed varying degrees of scattered muscle fiber necrosis and regeneration on muscle biopsies. In 1 patient, a small amount of inflammatory cell infiltration was observed. Pipestem capillaries were observed in 4 patients. Immunohistochemical staining revealed a small number of CD68-positive lymphocytes in 8 patients. Additionally, 5 patients showed upregulation of major histocompatibility complex Ⅰ expression on the muscle fiber membrane, while 6 patients showed deposition of membrane attack complex (C5b-9) on non-necrotic muscle fibers and capillaries. P62 staining showed homogeneous fine-granular in sarcoplasm in 6 patients.Conclusions:In addition to proximal muscle weakness, patients with SRP-IMNM often experience neck weakness and dysphagia. Those with multiple antibodies are more likely to develop interstitial lung disease and cardiac involvement. SRP-IMNM patients have diffuse oedema in the affected muscles, and the posterior thigh muscles are more prone to atrophy and fatty tissue formation. C5b-9 deposition and pipestem capillaries are significant pathological features of SRP-IMNM, which provide additional evidence for clinical diagnosis.
6.Nomogram for predicting the risk of post hepatectomy liver failure was established based on preoperative routine test indexes
Guoping DONG ; Chen CHEN ; Xudong LU ; Jiali WU ; Wenhao ZHENG ; Lin TONG
Chinese Journal of Laboratory Medicine 2024;47(8):895-901
Objective:To establish a risk prediction model of liver failure after liver resection for hepatocellular carcinoma.Method:A retrospective case-control study was designed. Clinical data and laboratory results, including gender, age, and preoperative 18 laboratory indicators, were collected from 320 patients with hepatocellular carcinoma undergoing liver resection in Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University from January 1, 2013 to December 31, 2023. According to the surgical time, 252 cases in the training cohort were divided into 62 and 190 cases with and without postoperative liver failure, respectively. Of the 68 cases in validation cohort, 34 developed postoperative liver failure and 34 did not. Binary Logistic regression analysis was used to conduct univariate analysis of gender, age, and 18 preoperative laboratory indicators, and multivariate analysis was carried out for significant results to determine the influencing factors of liver failure after liver resection for hepatocellular carcinoma, and Logistic regression model was established.Result:In the training cohort, indicators significantly associated with liver failure after liver resection for hepatocellular carcinoma included age ( P=0.016), platelets ( P=0.005), prealbumin ( P<0.001), and alkaline phosphatase ( P<0.001). Logistic regression was used to construct a nomogram model and draw a calibration curve by combining these four indicators. In the training cohort, the nomogram model showed good discriminability in predicting the risk of liver failure after hepatectomy for hepatocellular carcinoma. The area under the curve of was 0.82 (95% CI 0.76-0.88), and the sensitivity was 73% and specificity was 80% when the optimal cut-off value was 0.2646. In the validation cohort, the predictive performance of the nomogram model was comparable to that of the training cohort, with an area under the curve of 0.81 (95% CI 0.71-0.92), sensitivity of 82%, and specificity of 77%. Conclusion:Preoperative platelet and prealbumin decreases, alkaline phosphatase increases, and elderly patients are prone to liver failure after liver resection. The nomogram model constructed with preoperative test data has shows good discriminatory ability and accuracy in predicting liver failure after liver resection for hepatocellular carcinoma.
7.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.
8.FHL1 gene mutation related late-onset reducing body myopathy in a Chinese family
Wenhao CUI ; Qianqian QU ; Xianzhao ZHENG ; Xiaoli MA ; Yaguang ZHOU ; Shiyao LI ; Jiongbo ZHAO ; Haidong LYU
Chinese Journal of Neurology 2023;56(12):1349-1354
Objective:To summarize the characteristics of clinical, muscle pathology and gene mutation of late-onset reducing body myopathy caused by FHL1 gene mutation, in order to improve clinicians′ understanding of this disorder. Methods:The clinical, muscle pathology and muscle magnetic resonance imaging data of the proband from a family diagnosed as reducing body myopathy in Jiaozuo People′s Hospital in December 2021 were collected. Genetic tests and pedigree verification were conducted on the proband and her son.Results:The proband was a 59-year-old female with progressive, asymmetrical limb weakness and muscular atrophy. Her mother, sister and brother had similar symptoms. Electromyography showed myogenic and neurogenic damage. Muscle magnetic resonance imaging indicated that the lesion mainly involved the posterior muscles of the thigh and calf, as well as the gluteus maximus. The muscle pathology showed eosinophilic granular inclusion bodies and rimmed vacuoles in the muscle fibers of the lesion. The structure of myofibrils was disordered and abnormal protein deposition was observed. The gene sequencing showed the FHL1 gene p.C150S heterozygous variation. Conclusions:Late-onset reducing body myopathy is characterized by progressive asymmetric proximal limb muscle weakness, partially involving distal limb muscles and gluteus maximus. Muscle pathology shows the characteristic pathological changes of many kinds of myofibrillar myopathies. FHL1 gene mutation is an important basis for diagnosis.
9.Clinical application of a novel urinary cytology detection system for bladder cancer
Hui WANG ; Wenhao SHEN ; Zheng WANG ; Yiran HUANG
Journal of Modern Urology 2023;28(6):493-496
【Objective】 To investigate the diagnostic efficacy of a novel bladder cancer detection system utilizing a urine cell processing kit for urine sample preservation and detection. 【Methods】 Patients with primary persistent gross hematuria and high recurrence risk of bladder cancer after transurethral resection of bladder tumor were prospectively enrolled between Dec.2021 and Mar.2022. Urine specimens were either added to (experimental group) or not added to (control group) the urine cell processing kit and were fixed on Day 0, Day 3 and Day 7. The sensitivity and specificity of the two groups were compared after the cells were fixed, produced, stained and read with body fluid cytology total staining technique. 【Results】 The sensitivity and specificity of the experimental group on Day 0 were 82.50% (33/40) and 87.50% (14/16), respectively; those of the control group were 79.49% (31/39) and 82.35% (14/17), respectively. On Day 3, the sensitivity and specificity of the experimental group were 76.32% (29/38)and 81.25% (13/16), respectively; those of the control group were 52.78% (19/36) and 78.57% (11/14), respectively. On Day 7, the sensitivity and specificity of the experimental group were 71.43% (25/35) and 72.22% (13/18), respectively; those of the control group were 35.71% (10/28) and 60.00% (9/15), respectively. The sensitivity of the experimental group on Day 3 and Day 7 was significantly higher than that of the control group (P<0.05). 【Conclusion】 This bladder cancer urine cytology detection system provides clear diagnostic advantages and can be used as an auxiliary examination before cystoscopy for patients with hematuria and those at high risk of bladder cancer recurrence. It can also be used as a bladder cancer screening tool for pre-screening a large sample of people in order to achieve early diagnosis and treatment of bladder cancer.
10.The association between blood glucose levels of children with type 1 diabetes mellitus and parental educational levels based on mobile health APP
Dongxue ZHENG ; Wenhao ZHANG ; Xueying ZHENG ; Sihui LUO ; Jianping WENG ; Chaofan WANG
Journal of Chinese Physician 2023;25(3):330-334,341
Objective:To explore the correlation between blood glucose level and parental education level in children with type 1 diabetes mellitus (T1DM) based on mobile health APP.Methods:The data of T1DM children enrolled in China′s T1DM registration management program and registered to use TangTangquan ? were collected, as well as the blood glucose monitoring information uploaded quarterly after registration. Children were divided into low education group (middle school or below) and high education group (junior college or above) according to their parents′ education level. Blood glucose levels were compared between the two groups at different time points. Spearman correlation analysis and multivariate logistic regression analysis were used to evaluate the correlation between blood glucose level and parents′ education level in children with T1DM. Results:A total of 2 263 eligible children with T1DM were included and 1 246 were female (55.1%). The median age was 7.9(4.4, 11.4)years and T1DM duration was 0.07(0.02, 0.46)years. Among them, 1 513 cases were in the low-education group while 750 cases were in the high-education group. Within three years after registration, the glucose levels of each interval in the low-education group were increasing gradually (all P<0.05 except post-breakfast glucose). The glucose levels of each interval in the high-education group in the third year were lower than those in the low-education group (all P<0.05 except nocturnal glucose). The result of multivariate logistic regression analysis showed that after the adjustment of factors including T1DM duration and treatment, parental educational levels were still the separate related factors of premeal glucose, bedtime glucose and nocturnal glucose (premeal glucose: OR=0.385, 95% CI: 0.164-0.874, P=0.025; bedtime glucose: OR=0.444, 95% CI: 0.204-0.949, P=0.038; nocturnal glucose: OR=0.226, 95% CI: 0.582-0.747, P=0.020). Conclusions:The blood glucose levels of children with T1DM were negatively associated with parental educational levels. It is suggested that parental educational levels should be taken into consideration in the management of T1DM for children.

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