1.UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL
Renyu ZHANG ; Can LI ; Shuai ZHANG ; Lingmin KONG ; Zekun LIU ; Yixiao GUO ; Ying SUN ; Cong ZHANG ; Yule YONG ; Jianjun LV ; Meng LU ; Man LIU ; Dong WU ; Tianjiao ZHANG ; Haijiao YANG ; Ding WEI ; Zhinan CHEN ; Huijie BIAN
Clinical and Molecular Hepatology 2024;30(4):771-792
Background/Aims:
Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.
Methods:
Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth.
Results:
Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy.
Conclusions
UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.
2.Ultra-short-course and intermittent TB47-containing oral regimens produce stable cure against Buruli ulcer in a murine model and prevent the emergence of resistance for
Yamin GAO ; H M Adnan HAMEED ; Yang LIU ; Lingmin GUO ; Cuiting FANG ; Xirong TIAN ; Zhiyong LIU ; Shuai WANG ; Zhili LU ; Md Mahmudul ISLAM ; Tianyu ZHANG
Acta Pharmaceutica Sinica B 2021;11(3):738-749
Buruli ulcer (BU), caused by
3.Clinical application effect of repairing large area of skin and soft tissue defects of extremities
Liangjun ZHENG ; Ao GUO ; Zhenyu HUANG ; Yanquan JIN ; Lingmin CAI
Chinese Journal of Plastic Surgery 2021;37(4):423-429
Objective:This clinical study describes the surgical methods and clinical effects for large skin and soft tissue defects of the extremities.Methods:Between October 2005 and February 2019, the patients with large skin and soft tissue defects of the extremities were hospitalized in the Department of Hand Surgery of the Orthopedic Hospital of Taizhou. The choice of flaps for primary phase repair was determined by the degree and the type of defect, including anterolateral thigh (ALT) flap, latissimus dorsi myocutaneous flap (LDMF), combined free ALT flap and osteocutaneous fibula flap and vascularized iliac osteocutaneous flap based on superficial circumflex iliac artery (SCIA). The donor site was primarily closed. And the appearance and function of donor and recipient sites were followed up.Results:Forty-five cases were performed in this study. There were 33 males and 12 females. The ages of the patients ranged from 21 to 65 years with an average of 35.2 years. The size of the defects ranged from 7 cm×6 cm to 32 cm×12 cm, with bone defects in 14 cases. The recipient sites included the free ALT flap in 17 (ranged from 11 cm×7 cm to 30 cm×12 cm), LDMF in 14 (ranged from 10 cm×7 cm to 32 cm×12 cm), ALT (ranged from 9 cm×6 cm to 16 cm×8 cm) + osteocutaneous fibula flap(ranged from 6 cm×4 cm to 9 cm×5 cm ) in 6, and iliac osteocutaneous flap based on SCIA (ranged from 7 cm×6 cm to 13 cm×8 cm). Among the 45 cases, 44 cases survived. There was one case with dorsal foot defect, which reconstructed by ALT flap, had vascular crisis after surgery. Although the vascular exploration was timely, the flap eventually necrotic. The ALT flap on the other side was successfully reapplied. Patients were followed up for average 4 years (ranging from 1-13 years), and all of them were satisfied with the function and final aesthetic outcomes. The two-point discrimination of the flap was 5 mm to 10 mm. The donor site healed well. There was no obvious scar hyperplasia except the latissimus dorsi donor.Conclusions:According to the size and depth of the large area of skin and soft tissue defects of extremities, and whether there are tendon, muscle and bone defects, a reasonable scheme is selected for repair, which can obtain good appearance and function after surgery, and less damage to the donor site.
4.Clinical application effect of repairing large area of skin and soft tissue defects of extremities
Liangjun ZHENG ; Ao GUO ; Zhenyu HUANG ; Yanquan JIN ; Lingmin CAI
Chinese Journal of Plastic Surgery 2021;37(4):423-429
Objective:This clinical study describes the surgical methods and clinical effects for large skin and soft tissue defects of the extremities.Methods:Between October 2005 and February 2019, the patients with large skin and soft tissue defects of the extremities were hospitalized in the Department of Hand Surgery of the Orthopedic Hospital of Taizhou. The choice of flaps for primary phase repair was determined by the degree and the type of defect, including anterolateral thigh (ALT) flap, latissimus dorsi myocutaneous flap (LDMF), combined free ALT flap and osteocutaneous fibula flap and vascularized iliac osteocutaneous flap based on superficial circumflex iliac artery (SCIA). The donor site was primarily closed. And the appearance and function of donor and recipient sites were followed up.Results:Forty-five cases were performed in this study. There were 33 males and 12 females. The ages of the patients ranged from 21 to 65 years with an average of 35.2 years. The size of the defects ranged from 7 cm×6 cm to 32 cm×12 cm, with bone defects in 14 cases. The recipient sites included the free ALT flap in 17 (ranged from 11 cm×7 cm to 30 cm×12 cm), LDMF in 14 (ranged from 10 cm×7 cm to 32 cm×12 cm), ALT (ranged from 9 cm×6 cm to 16 cm×8 cm) + osteocutaneous fibula flap(ranged from 6 cm×4 cm to 9 cm×5 cm ) in 6, and iliac osteocutaneous flap based on SCIA (ranged from 7 cm×6 cm to 13 cm×8 cm). Among the 45 cases, 44 cases survived. There was one case with dorsal foot defect, which reconstructed by ALT flap, had vascular crisis after surgery. Although the vascular exploration was timely, the flap eventually necrotic. The ALT flap on the other side was successfully reapplied. Patients were followed up for average 4 years (ranging from 1-13 years), and all of them were satisfied with the function and final aesthetic outcomes. The two-point discrimination of the flap was 5 mm to 10 mm. The donor site healed well. There was no obvious scar hyperplasia except the latissimus dorsi donor.Conclusions:According to the size and depth of the large area of skin and soft tissue defects of extremities, and whether there are tendon, muscle and bone defects, a reasonable scheme is selected for repair, which can obtain good appearance and function after surgery, and less damage to the donor site.
5.Item d560 of the ICF is effective in assessing the swallowing function of convalescing stroke patients
Weiwen XU ; Yang CHEN ; Yun HAN ; Lin GUO ; Yanyan FENG ; Lingmin WANG ; Jie XIANG
Chinese Journal of Physical Medicine and Rehabilitation 2021;43(7):607-610
Objective:To investigate the correlation between item d560 of the International Classification of Functioning, Disability and Health (ICF) and the swallowing function of convalescing stroke patients.Methods:A total of 140 convalescent stroke survivors were evaluated for dysphagia using the ICF-d560 and the modified Watian drinking water test. Linear regression was used to analyze the influence of clinical factors when choosing a swallowing function assessment scale. Spearman correlation was computed to explore the correlation between ICF item d560 and the modified Watian drinking water test.Results:According to the ICF-d560 results, 10% of the patients had a mild disorder, with another 37.1% moderate, 29.3% severe and 23.6% completely dysphagic. The corresponding percentages according to the improved Watian drinking water test were 44.3% mild, 31.4% moderate and 24.3% severe. The total correlation coefficient between the two sets of results was 0.86, which was related to the stroke type, age, gender and stroke risk factors. The correlation coefficient of the cerebral infarction group was significantly higher than the cerebral hemorrhage group′s coefficient, and that of the women was slightly higher than that of the men. The strength of the correlation increased with age. The correlation coefficient was 0.84 among both diabetics and hypertension sufferers.Conclusions:Results from the ICF-d560 and the modified Wada drinking water test correlate well, which can provide a screening tool for swallowing function based on the ICF theoretical framework.
6.Free chimeric anterolateral thigh cutaneotendinous flap with rectus femoris muscular flap for repairing the complex tissue defect of dorsum wrist
Ao GUO ; Dajiang SONG ; Liangjun ZHENG ; Yanquan JIN ; Lingmin CAI ; Zan LI ; Xiao ZHOU
Chinese Journal of Microsurgery 2018;41(5):454-458
Objective To explore the clinical outcome of free chimeric anterolateral thigh cutaneotendinous flap with rectus femoris muscular flap for repairing the complex tissue defect of dorsum wrist. Methods From June, 2005 to March, 2014, free chimeric anterolateral thigh cutaneotendinous flap with rectus femoris muscular flap was used for repairing the complex tissue defect of dorsum wrist in 15 cases, which were 12 males and 3 females, and aged from 18 to 52 years old. The skin and soft tissue defect ranged from 8.0 cm×5.5 cm to 22.0 cm×12.0 cm. All ac-companied with extensor digitorum tendon loss. The tendon defect ranged from 5.0 cm to 12.0 cm (7.6 cm on average). The flap size ranged from 9.0 cm×6.5 cm to 23.0 cm×13.0 cm. The pedicle length ranged from 4.0 cm to 7.0 cm (5.3 cm on average). Results All flaps survived, and no postoperative complications occurred. The followed-up time ranged from 12 months to 36 months, and the texture of flap was flexible. No bulky was noted, and skin color was similar to the hand skin. The flexor and extensor function of wrist recovered satisfying. The 2-point discrimination of flap ranged from 9 mm to 15 mm (12.5 mm on average). Conclusion Free chimeric anterolateral thigh cutaneo-tendinous flap with rectus femoris muscular flap is a good option for repairing the complex tissue defect of dorsum wrist.
7. Relationship between expressions of OCT-4, CD117 and clinicopathological features and prognosis of patients with ovarian cancer
Aiqi QIAO ; Qinghua LIU ; Yanfeng XI ; Linzhi GUO ; Dongmei LIU ; Lingmin LI
Cancer Research and Clinic 2018;30(8):516-520
Objective:
To investigate the relationship between expressions of OCT-4, CD117 and clinicopathological features and prognosis of patients with ovarian cancer.
Methods:
A total of 70 paraffin-embedded tissues of patients with ovarian cancer from January 2010 to February 2016 in Shanxi Provincial Cancer Hospital were collected. The expressions of OCT-4 and CD117 were detected by immunohistochemistry.
Results:
OCT-4 was mainly expressed in cytoplasm, while CD117 was expressed in cell membrane and cytoplasm. The positive expression rate of OCT-4 was 74.3% (52/70), and the positive expression rate of CD117 was 68.6% (48/70). The positive expression rates of OCT-4 in ovarian cancer tissues with poorly differentiation and high CA125 levels (≥500 U/ml), no peritoneal effusion and sensitive to chemotherapy drugs were 92.1% (35/38), 87.5% (28/32), 88.9% (24/27), and 78.7% (48/61), respectively, which were higher than those in ovarian cancer tissues with well and moderately differentiation, low CA125 levels (<500 U/ml), peritoneal effusion and resistance to chemotherapy drugs, the differences were statistically significant (
8.The value of prenatal ultrasound in diagnosis of fetal meningocele or encephalocele
Fenglian DENG ; Yanli GUO ; Lingmin DUAN ; Yujie FENG ; Hua ZHONG ; Jianjun LIU ; Yafang XUE
Chongqing Medicine 2017;46(4):475-477
Objective To investigate the clinical value of prenatal ultrasound in fetal meningocele and encephalocele.Methods Thirty nine fetuses with meningocele and encephalocele confirmed by prenatal ultrasound and abortion were acquired and their clinical data and sonographic features were retrospectively analyzed.Results Ultrasound screening in 111 620 cases showed 39 fetuses were with meningocele and encephalocele,accounting for 0.35%.Among them,16 cases were diagnosed with meningocele (including 1 case with two bulging parts) and 23 cases with encephalocele.Prenatal ultrasound could clearly detect the location and size fetal skull defect,and bulging features.According to their sonographic features,meningocele or encephalocele was determined.Conclusion Ultrasound could be a reliable prenatal screening method,provide an important basis for clinical intervention and have a significant clinical value in fetal meningocele and encephalocele.
9.Left Atrial Appendage Occlusion Under the Guidance of Local Anesthesia and Modified Transseptal Puncture Technology
Lihui ZHENG ; Lingmin WU ; Wei SUN ; Jinyue GUO ; Yu QIAO ; Ligang DING ; Gang CHEN ; Yan YAO
Chinese Circulation Journal 2017;32(7):646-649
To explore the safety and efficacy of left atrial appendage (LAA) occlusion under the guidance of local anesthesia and modified transseptal puncture technology by coronary sinus assisted positioning in patients with nonvavular atrial fibrillation (NVAF). Methods: A total of 16 NVAF patients received local anesthesia and percutaneous LAmbre or Amplatzer cardiac plug occluder implantation. There were 12 males and the patients mean age was at (71.0±6.0) years with CHA2DS2-VASc score at (4.1±1.5); all patients had walfarin contradiction or with walfarin related side effect. Transseptal puncture was conducted by coronary sinus catheter as the anatomic location marker. Results: All 16 patients finished transseptal puncture and no relevant complication occurred. 15/16 (93.8%) patients had successful LAA occlusion, 1 patient was abandoned because of LAA anatomic structure variation. The mean operative time was (65.0±23.0) min and the mean X-ray exposure time was (12.0±3.0) min. The mean diameter of occluder was (32.5±6.0)mm. Conclusion: LAA occlusion was safe and effective with local anesthesia and modified transseptal puncture technology by coronary sinus assisted positioning in relevant patients.
10.Relationship between mismatch repair protein expression and clinicopathological features of endometrial cancer
Junhui GUO ; Dongmei LIU ; Aiqi QIAO ; Qinghua LIU ; Yanfeng XI ; Lingmin LI
Cancer Research and Clinic 2017;29(10):649-652,666
Objective To screen out probable lynch syndrome (LS) associated endometrial cancer (EC) by investigating the expression of mismatch repair (MMR) protein in EC, and to analyze the disease traits combined with clinicopathologic characteristics. Methods The expressions of MSH2, MSH6, MLH1 and PMS2 were detected by using immunohistochemistry (IHC) in 443 EC patients. Results In 443 EC patients, 328 cases (74%) with all MMR proteins expression were classified as sporadic EC, and 115 cases (26%) cases with loss expression of at least one MMR protein were regarded as probable LS. MMR-deficient cases mostly showed a loss of MLH1/PMS2 expression (42%), followed by the absence of MSH2/MSH6 (23%), MSH6 (17%), PMS2 (17%) and MSH6/MLH1/PMS2 (3%). Compared with the sporadic EC group, obesity was not found in probable LS group (body mass index<28 kg/m2) (P=0.040), and high tumor grade was common (P=0.012); There was no significant difference between the two groups in age, the incidence of diabetes or hypertension, family history of cancer or histological type, tumor location, the International Federation of Gynecology and Obstetrics (FIGO) stage, myometrial invasion, lymph node metastasis, lymphatic or vascular invasion (all P> 0.05). A higher tumor grade was more common in the MSH6 and PMS2 deficient groups. Conclusions Compared with sporadic EC, the absence of obesity, a high grade tumor are more common in probable LS cases.

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