Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Objective To investigate the expression and clinical significance of microRNA-93-5p (miR-93-5p) in patients with type 2 diabetes mellitus (T2DM) complicated with coronary heart disease (CHD). Methods A total of 60 patients with T2DM (T2DM group), 57 patients with T2DM complicated with CHD (T2DM with CHD group), and 60 healthy individuals (control group) were enrolled in this study from August 2019 to May 2021. The general information, serum miR-93-5p, and interleukin-6 (IL-6) levels were compared among the T2DM with CHD group, control group and T2DM group; the relationships of serum miR-93-5p and IL-6 levels with low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), triglyceride (TG), glycated hemoglobin (HbA1c), and total cholesterol (TC) were analyzed in T2DM with CHD patients; the influencing factors of T2DM complicated with CHD were analyzed; the predictive value of serum miR-93-5p and IL-6 for T2DM complicated with CHD was evaluated. Results The levels of LDL-C, FINS, TG, FPG, TC, HbA1c, serum miR-93-5p, and IL-6 in the T2DM with CHD group and T2DM group were significantly higher than those in the control group, while the HDL-C level was significantly lower (P < 0.01); the levels of LDL-C, FINS, TG, FPG, TC, HbA1c, serum miR-93-5p, and IL-6 in the T2DM with CHD group were significantly higher than those in the T2DM group, while the HDL-C level was significantly lower (P < 0.01). The serum miR-93-5p and IL-6 levels in T2DM with CHD patients were positively correlated with LDL-C, FINS, HbA1c, TC and FPG (P < 0.01), and negatively correlated with HDL-C (P < 0.01); the expression level of miR-93-5p in serum was positively correlated with IL-6 (P < 0.05). LDL-C, FINS, FPG, HbA1c, TC, miR-93-5p, and IL-6 were the influencing factors of T2DM complicated with CHD (P < 0.05); the area under the curve (AUC) of serum miR-93-5p and IL-6 for predicting T2DM complicated with CHD was 0.888 and 0.898 respectively, with cut-off values of 2.59 and 77.98 ng/L respectively, sensitivity of 75.4% for both serum miR-93-5p and IL-6, and the specificity was 89.2% for miR-93-5p and 85.8% for IL-6; the AUC of the combined prediction of miR-93-5p and IL-6 for T2DM complicated with CHD was 0.939, with sensitivity and specificity of 91.2% and 83.3% respectively. Conclusion The serum miR-93-5p level is elevated in patients with T2DM complicated with CHD, and miR-93-5p together with IL-6 may participate in the process of T2DM complicated with CHD. The combined detection of IL-6 and miR-93-5p is expected to serve as an auxiliary method for prediction of T2DM complicated with CHD.

Objective:To evaluate the clinical effect of laparoscopic surgery after transformation therapy for patients with stage Ⅳ gastric cancer.Methods:Clinical data of 55 patients with stage Ⅳ gastric cancer underwent transformation therapy at Zhejiang Provincial People′s Hospital from January 2018 to January 2021 were reviewed retrospectively. All patients had distant metastasis and underwent multi-disciplinary treatment (MDT) directed transformation therapy. 21 patients was appraised to have indications of laparoscopic exploration. Of which 18 patients underwent D2 radical laparoscopic gastrectomy, 1 patient underwent gastrojejunostomy and 2 patient underwent laparoscopic biopsy. The remission of patients after conversion therapy and the related intraoperative and postoperative indicators were analyzed.Results:After the transformation therapy, there were 2 cases of complete response (CR), 22 cases of partial response (PR), 14 cases of stable disease (SD) and 17 cases of progressive disease (PD). The objective response rate was 69.09%(38/55). 18 cases finally completed laparoscopic gastric cancer surgery (1 case converted to laparotomy), including total gastrectomy in 10 cases, distal gastrectomy in 8 cases, and R0 resection in 12 cases (R0 resection rate 12/18). In all 18 cases, the surgical time was (223±28)min, the intraoperative blood loss was (100±48)ml, and the number of lymph nodes resected was (28±8). The median postoperative hospital stay was 12(10.25, 19.25)d. After surgery, there were 2 cases of grade Ⅲ complications, 5 cases of grade Ⅱ complications and 1 case of grade Ⅰ complications. There was no perioperative death. The 1-year survival rate was 12/18. The median progression-free survival time was 11 months and the median overall survival time was 19 months.Conclusions:Laparoscopic surgery for stage Ⅳ gastric cancer after transformation therapy is safe and clinical effect is fine.

Objective:To compare closed reduction and intramedullary nailing versus open reduction and locking plate fixation in the treatment of middle and upper humeral fractures.Methods:A retrospective case-control study was conducted to analyze the clinical data of 62 patients with middle and upper humeral fracture who had been treated at Department of Orthopaedics, The First People's Hospital of Jinmen and at Department of Orthopedics, General Hospital of PLA Central Theater from October 2017 to February 2021. There were 35 males and 27 females, aged from 27 to 86 years. The left side was affected in 24 cases and the right side in 38 cases. All fractures were fresh. According to the AO classification, 16 cases were type A, 32 type B, and 14 type C. Of the patients, 29 were treated with closed reduction and intramedullary nailing (intramedullary nail group) and 33 with open reduction and locking plate fixation (locking plate group). The length of incision, operation time, intraoperative blood loss, hospital stay, fracture healing and complications were recorded and compared between the 2 groups. The pain degree was evaluated by visual analogue scale (VAS) at one week and one month after operation, and the functional recovery of the shoulder was evaluated by Constant-Murley score at one month and 12 months after operation.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The intramedullary nail group was followed up for 12 to 29 months and the locking plate group for 15 to 50 months. In the intramedullary nail group, the length of incision [(4.1±0.7) cm], operation time [(58.3±7.7) min], intraoperative blood loss [(52.7±6.5) mL], and hospital stay [(7.3±1.5) d] were significantly less than those in the locking plate group [(21.7±2.3) cm, (95.8±11.7) min, (237.4±14.9) ml, and (12.3±1.7) d] ( P<0.05). The fracture healing time in the intramedullary nail group was (5.0±1.9) months, significantly longer than that in the locking plate group [(3.5±1.7) months] ( P<0.05). The VAS scores at one week and one month after operation in the intramedullary nail group [(2.8±0.3) points and (1.2±0.5) points] were significantly lower than those in the locking plate group [(4.3±0.4) points and (1.6±0.5) points], and the Constant-Murley score at one month after operation in the intramedullary nail group [(63.5±7.4) points] was significantly higher than that in the locking plate group [(54.3±6.9) points] ( P<0.05). However, at 12 months after operation, there was no significant difference in the Constant-Murley score between the 2 groups ( P>0.05). In both groups, the VAS score at one month after operation was significantly lower than that at one week after operation while the Constant-Murley score at 12 months after operation was significantly higher than that at one week after operation ( P<0.05). In the intramedullary nail group, intraoperative distal refracture happened in one case; in the locking plate group, incision infection occurred in one case and postoperative radial nerve injury in another. There was no significant difference in the incidence of complications between the 2 groups [3.4% (1/29) versus 6.1% (2/33)] ( P>0.05). Conclusion:In the treatment of middle and upper humeral fractures, compared with open reduction and locking plate fixation, closed reduction and intramedullary nailing shows advantages of a smaller surgical incision, shorter operation time, less intraoperative blood loss, shorter hospital stay and faster functional recovery.

Objective:To investigate the changes of skeletal muscle-derived microparticles (SKMPs) and their scaving proteins lactadherin in peripheral blood of patients with perihip fractures and their effects on blood coagulation. It provides a theoretical basis for clinical evaluation of hypercoagulability in patients with perioperative hip fractures.Methods:A total of 44 patients (72.87±13.9 years old) with perihip fractures from October 2020 to January 2021 were included in the fracture group, and 40 healthy people were included in the group without fracture. Activated clotting time (ACT) in fracture group and control group was measured by coagulation and platelet function analyzer. The level of SKMPs in peripheral venous blood was determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of MPs scaving proteins lactadherin in peripheral blood of fracture group and control group.Results:A total of 44 patients with perihip fractures were included. There were 33 (75%) femoral neck fractures and 11 (25%) intertrochanteric fractures. SKMPs concentration in peripheral blood of perihip fracture group 175.73/μl; postoperative fracture group 124.28/μl; Normal control group 90.69/μl. ACT was (377.5±76.2) s in the perihip fracture group, (498.1±97.1) s in the post-fracture group, and (505.7±44.0) s in the control group. Correlation analysis showed that there was a linear relationship between SKMPs count and ACT value in fracture patients ( r=-0.52, P<0.001). There was no significant correlation between SKMPs concentration and ACT value in peripheral venous blood of the post-fracture group ( P>0.05); Lactadherin protein concentration in perihip fracture group: 2 779.61 pg/ml; Fracture postoperative group 1 985.38 pg/ml; Normal control group 1 651.19 pg/ml. There is a positive correlation between Lactadherin concentration and SKMPs concentration with a correlation coefficient of 0.70. Conclusion:SKMPs plays a role in the hypercoagulability of patients with perihip fractures. Decompensation of lactadherin protein may be one of the causes of perioperative hypercoagulation in patients with hip fractures.

OBJECTIVE: To determine the carrier rate of deafness-related genetic variants among 53 873 newborns from Zhengzhou. METHODS: Heel blood samples of the newborns were collected with informed consent from the parents, and 15 loci of 4 genes related to congenital deafness were detected by microarray. RESULTS: In total 2770 newborns were found to carry deafness-related variants, with a carrier rate of 5.142%. 1325 newborns (2.459%) were found to carry heterozygous variants of the GJB2 gene, 1071 (1.988%) were found with SLC26A4 gene variants, 205 were found with GJB3 gene variants (0.381%), and 120 were found with 12S rRNA variants (0.223%). Five newborns have carried homozygous GJB2 variants, two have carried homozygous SLC26A4 variants, five have carried compound heterozygous GJB2 variants, and four have carried compound heterozygous SLC26A4 variants. 33 neonates have carried heterozygous variants of two genes at the same time. CONCLUSION The carrier rate of deafness-related variants in Zhengzhou, in a declining order, is for GJB2, SLC26A4, GJB3 and 12S rRNA. The common variants included GJB2 235delC and SLC26A4 IVS7-2A>G, which are similar to other regions in China. To carry out genetic screening of neonatal deafness can help to identify congenital, delayed and drug-induced deafness, and initiate treatment and follow-up as early as possible.

Objective To explore the influences of continued nursing care on the recovery of intra-articular fractures of joint function of limbs and the quality of life after operation. Methods A total of 493 intra-articular fracture of limbs postoperative patients,who were discharged from our department from January 2015 to December 2016,were randomly divided into observation group and reference group.After operation,the reference group used self-management mode to practice joint functional exercise,while the observation group uses continued nursing mode to guide physical therapy to recover joint functions.After they discharged 12 weeks,we compared these two groups of patients with satisfaction of nursing care,joint function recovery and quality of life. Results After 12 weeks of operation, in observation group, the patients' joint function recovery rate was close to 79.27%(195/246), which was significantly higher than the rates 55.47%(137/247)in reference group,the difference was statistically significant(χ2=32.947,P<0.01). Respectively, the physiological function score,vigor score, mental health score, physiology role score, body pain score, health condition score, social function score and health score of the observation group in the quality of life assessment were (72.66 ± 4.41), (89.27 ± 4.10), (93.01 ± 3.05), (88.03 ± 3.19), (91.68±3.99),(76.78±4.86),(79.11±4.68),(85.57±7.07).The scores of control groups were(65.71±3.41),(64.02±4.51),(61.43±4.29),(66.49±4.52),(64.24±4.30),(62.02±6.24),(62.94±4.50),(65.02±7.72).The comparative difference of the two groups has statistical significance (t=12.48- 60.15, P<0.05). Meanwhile,in the satisfaction rate of nursing care,the great satisfaction rate of observation group(70.73%, 174/246) was much higher than reference group (37.65%, 93/247), the difference was statistically significant (χ2=59.789, P<0.01). Conclusion Offered outside continued nursing care to the intra-articular fracture of limbs postoperative patients can effectively improve the joint function of patients,their qualities of life and can considerably increase satisfaction of nursing care. Thus,it should to be clinically promoted.

Objective To observe the effects of Weipixiao on the ultrastructure of gastric mucosa capillaries in rats with precancerous lesions of gastric cancer ( PLGC). Methods The rats were randomized into six groups, including normal group, model group, Vatacoenayme Tablets group ( 0.2 g·kg-1·d-1) , and high-, middle-, and low- dose Weipixiao groups ( 15, 7.5, and 3.75 g·kg-1·d-1 respectively) . The rats received spontaneous intake of N-methyl-N’-nitro-nitrosoguanidine ( MNNG, 200 μg/mL) solution combined with irregular diet and intragastric administration of purgative herbs Xiao Chengqi Decoction ( 2 mL, containing 1 g/mL crude drug) for 18 weeks to induce spleen-deficiency PLGC. The pathological changes in gastric mucosa and the ultrastructure of gastric mucosa capillaries were observed under the transmission electron microscope. Results The model has been established successfully. Transmission electron microscopy results in the model group showed as severely swollen endothelial cells of gastric mucosa capillaries, severely-narrowing or even blocked vascular lumens, rough and discontinuous basement membrane, and swollen, degenerated or even absent pericytes. And the ultrastructure of gastric mucosa capillaries in high-, middle-, and low- dose Weipixiao groups were improved to some degrees, the effect of low-dose Weipixiao group being the best. Conclusion The improvement of the mucosal microcirculation of spleen-deficiency PLGC rats may be one of the pathohistological mechanisms of Weipixiao for spleen-deficiency PLGC.

Objective To investigate the forming mechanism of smile anatomically,and to analyze the changes of aging characteristics of mid-lower face.Methods Ten (with 20 sides) adult fresh cadaveric heads were fixed by formalin,and then nasolabial fold morphology was observed under 10X operating magnifying glass,and compared with alteration of the middle and lower face aging features under the state of smiling and static according to observation from 50 doctors' and out-patients' photos.Results The nasolabial fold was the boundary between fatty and fat-free zone in the middle face,the lateral side of which was malar fat pad.The nasolabial fold was the linear area,which was formed by the insertions of seven mimetic muscles on the skin.When smiling,the nasolabial fold and cheek groove,got deep and extended,cheek stripe became obvious.While smiling,malar fat pad shifted up,and tear trough became deformity..64％ disappeared and 36％ getting shallow and appearance improved; orbit-malar fold showed 100％ horizontal part disappeared,74 ％ vertical part became shallow and improved,and 26％ stayed stable; mid-cheek fold showed 78％ dissovled,22％ getting shallow and improved; Labiomandibular fold showed 100％ Ⅲ degree disappeared,100％ Ⅱ degree dissovled,74％ Ⅰ degree disappeared,and 26％ getting shallow and ameliorated; submaxilla line showed 18％ getting smooth and 82％ remained.Conclusions Smiling is produced by movement of mimetric muscles,and its orgin is from nasolabial fold.A smile could make malar fat pad upwards to mask some aging characteristics of middle and lower face,which is helpful to form a younger face.

OBJECTIVETo explore the mechanism of the aging deformity of tear trough through the anatomic study of the tear trough region.

METHODS13 adult cadaveric heads (26 sides), including 9 male heads (18 sides) and 4 female heads (8 sides), aged 22-78 years old, were used. Anatomic study was performed around the orbital, especially tear trough region, with microsurgery instrument under microscope( x 10 times). The lower orbicularis retaining ligament was dissected and exposed. The anatomic location was recorded and photographed.

RESULTS(1) The anatomic layers of the tear trough region contains skin, subcutaneous tissue, orbicularis oculi muscle, periosteal membrane. There is no subcutaneous fat above the tear trough, while it exists below the tear trough, called malar fat pad. (2) There is a natural boundary between the septal and the orbital portions of the orbicularis oculi muscle of lower eyelid at surface of the orbital bone. The natural boundary, projected on the body surface corresponds to tear trough. The width of boundary is (2.06 +/- 0.15) mm on the vertical line through inner canthus and (3.25 +/- 0.12) mm on the vertical line through the lateral margin of the ala. The septal portion and the orbital portion of the orbicularis oculi muscle began to merge in (16.56 +/- 0.51) mm to inner canthus. (3) There is ligament attachment in the medial, upper and lower orbital and no ligament attachment in the lateral orbital. Orbicularis retaining ligament of lower eyelid is divided into two layers. (4) The medial of the upper layer of the orbicularis retaining ligament in lower eyelid originates from orbital margin and from preorbital walls laterally in (16.10 +/- 0.43) mm to the medial of lateral orbital margin, through orbicularis oculi muscle and ends at the skin. The lower layer of the orbicularis retaining ligament of lower eyelid originates from preorbital walls through orbicularis oculi muscle and its superficial fat, then ends at the skin.

CONCLUSIONSThe length of tear trough is (16.56 +/- 0.51) mm, the width of tear trough is (2.06 +/- 0.15) mm and (3.25 +/- 0.12) mm on the vertical line through inner canthus and the lateral margin of the ala nasi respectively. The main reason of the aging deformity of tear trough attributes to the increased distance between the upper and lower layers of the orbicularis retaining ligament in lower eyelid, which is caused by loose of the orbicularis retaining ligament and its underlying fat atrophy or decline.

Adult ; Aged ; Aging ; Cheek ; anatomy & histology ; Eyelids ; anatomy & histology ; Facial Muscles ; anatomy & histology ; Female ; Humans ; Lacrimal Apparatus ; anatomy & histology ; Male ; Middle Aged ; Young Adult