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.

Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P＜0.05),while the expression of serum IL-10 was significantly decreased(P＜0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P＜0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P＜0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P＜0.05),and the serum IL-10 level was increased(P＜0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P＞0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.

Objective:To investigate the risk factors of bone cement leakage after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF).Methods:A multi-center, large-sample, case-control study was carried out to analyze the clinical data of 2 273 OVCF patients (2 689 vertebrae) undergone PVP at four hospitals between May 2018 and October 2021, including 994 males and 1 279 females, with the age of 52-91 years [(69.1±3.1)years]. Of all, 581 patients (604 vertebrae) were allocated to leakage group and 1 692 patients (2 085 vertebrae) to no leakage group according to the occurrence of bone cement leakage. The gender, age, fracture sites, vertebral compression degree, endplate integrity of fractured vertebrae, surgical segments, surgical approaches and bone cement injection volume were recorded. Univariate analysis was used to investigate the correlation between those indicators with bone cement leakage. Multivariate Logistic regression analysis was used to identify the independent risk factors for bone cement leakage.Results:Univariate analysis showed that gender, age, fracture sites, vertebral compression degree, bone cement injection volume were related to bone cement leakage after PVP ( P<0.05 or 0.01), but no correlation was found in the endplate integrity of fractured vertebrae, surgical segments and surgical approaches (all P>0.05). Multivariate Logistic regression analysis showed that fracture sites ( OR=1.68, 95% CI 1.11-2.55, P<0.05), vertebral compression degree more than 40% ( OR=1.98, 95% CI 1.29-3.02, P<0.01), bone cement injection volume greater than or equal to 5.5 ml ( OR=1.55, 95% CI 1.07-2.26, P<0.05) were significantly associated with bone cement leakage after PVP. Conclusion:Thoracic vertebral fracture, vertebral compression degree more than 40% and bone cement injection volume greater than or equal to 5.5 ml are independent risk factors for bone cement leakage after PVP in OVCF.

Objective:To investigate the effects of different connection schemes of continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) on arterial pressure (PA), venous pressure (PV), and transmembrane pressure (TMP), and to provide a theoretical basis for choosing a suitable connection scheme.Methods:① In vitro study: the different connection schemes of CRRT and ECMO were simulated and divided into 6 schemes according to the connection between CRRT and ECMO circuits at different positions. Scheme A: connected to the front and back points of the oxygenator; scheme B: connected to the points behind and in front of the oxygenator; scheme C: connected to the points in front of the oxygenator and in front of the centrifugal pump; scheme D: connected to the points behind the oxygenator and in front of the centrifugal pump; scheme E: connected to the points in front of the oxygenator and the return catheter; scheme F: connected to the points after the oxygenator and the return catheter. Each set of ECMO circuits was measured 5 times under each connection scheme and different flow rates (2, 3, 4, 5, 5.5 L/min). Six ECMO circuits for a total of 30 measurements, and the PA, PV, and TMP of the 6 schemes were compared. ② In vivo study: the patients who were treated with ECMO combined with CRRT in the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from August 2017 to August 2021 changed the connection scheme due to high PA or PV (from scheme A or B to scheme E or F) were retrospectively analyzed. The changes of PA and PV before and after changing the scheme were compared. Results:① In vitro study results: there was no significant difference in PA between schemes A and B, C and D, E and F under different ECMO blood flow (2-5.5 L/min). The PA of schemes C and D was the lowest, followed by schemes E and F. PV of scheme B was higher than that of scheme A under different ECMO blood flow (2-5.5 L/min). There was no significant difference in PV between schemes C and D, E and F under high ECMO blood flow (3-5.5 L/min), and the absolute value of PV was lowest in schemes E and F. Compared with schemes A and B [partial PA > 300 mmHg (1 mmHg≈0.133 kPa) at high flow rate], C and D (partial PV > 350 mmHg at high flow rate), schemes E and F were more reasonable connection schemes. TMP was negative in schemes C and D at ECMO blood flow of 5 L/min and 5.5 L/min (mmHg; 5 L/min: scheme C was -29.14±11.42, scheme D was -42.45±15.70; 5.5 L/min: scheme C was -35.75±13.21, scheme D was -41.58±15.42), which indicated the presence of dialysate reverse filtration. Most of the differences in TMP among schemes A, B, E, and F under different ECMO blood flow (2-5.5 L/min) were statistically significant, and the absolute value of mean fluctuation was 9.89-49.55 mmHg, all within the normal range. ② In vivo study results: a total of 10 patients who changed the connection scheme (from scheme A or B to E or F) due to high PA or PV were enrolled, including 8 males and 2 females; 7 cases of venous-arterial ECMO (VA-ECMO) and 3 cases of venous-venous ECMO (VV-ECMO), all used continuous veno-venous hemodiafiltration (CVVHDF) mode. After changing the scheme, both PA and PV decreased significantly as compared with those before changing [PA (mmHg): 244.00±22.58 vs. 257.20±21.92, PV (mmHg): 257.20±18.43 vs. 326.40±15.41, both P < 0.01], and PV decreased more significantly than PA [difference (mmHg): 69.20±6.55 vs. 13.20±5.45, P < 0.01]. Conclusion:For patients treated with ECMO in combination with CRRT, the scheme of connecting the access line of CRRT to the pre-oxygenator or post-oxygenator and connecting the return line to the point of the return catheter can significantly reduce PA and PV and maintains normal CRRT operation even running high-flow ECMO.

Objective:To demonstrate the concept of planning target volume (PTV) is not suitable for intensity proton therapy (IMPT) in lung cancer, plan differences were compared based on the concept of PTV and Internal target volume (ITV), aiming to provide clinical reference.Methods:Six patients were retrospectively selected and approved by the local ethics committee. Each of the six patients received two IMPT plans based on a synchronous accelerator model, developed by SINAP team (Shanghai Institute of Applied Physics, China Academy Science University) and commercial treatment system: one with the PTV-based robust IMPT (PTV-IMPT) plan and the other with ITV-based robust IMPT (ITV-IMPT) plan. Three beams were set in all plans, and the final dose was calculated using Monte Carlo dose algorithm. The plan quality and robustness of PTV-IMPT and ITV-IMPT plans were evaluated quantitatively.Results:Compared to the PTV-IMPT plan, ITV-IMPT plan showed better target conformity index (conformability index: 0.58 vs.0.43), better homogeneity index (homogeneity index: 0.96 vs.0.92), lower V 5Gy in normal lung tissue (13.1% vs.13.5%) and maximum dose in spinal cord (8.9 Gy vs. 9.5 Gy) as well as plan monitor unit (MU: 338 vs. 401) . In addition, ITV-IMPT plan showed more robust in target coverage (0.003-0.032 vs. 0.02-0.28), and normal lung tissue was also found a bit robust in the ITV-IMPT plan ( 0.06-0.11, 0.07-0.13). Conclusions:Compared with the PTV-IMPT plan, ITV-IMPT plan has the advantages of high planning quality, well robustness and better tumor motion mitigation. Therefore, ITV concept is recommended to be applied in the IMPT plan for lung cancer.

Objective To investigate the effect of iliac flap pedicled with superficial circumflex iliac artery and sartorius in the treatment of femoral neck fracture of the young adults.Methods From April,2012 to March,2017,50 cadaveric lower limbs were injected with red latex,and the origin,diameter,course and distribution of the superficial circumflex iliac artery and arteries of the sartorius were observed.The iliac flap pedicled with superficial circumflex iliac artery and sartorius was used to treat the femoral neck fracture in young adults in 11 cases.There were 9 males and 2 females with an average age of 34.5(ranged from 16 to 54) years.The fractures were classified ac cording to Garden:4 cases of type Ⅲ and 7 cases of type Ⅳ.Regular outpatient follow-up was made.Results The superficial circumflex iliac artery originated from the femoral artery and the initial diameter was (1.2±0.3) mm.The length of the superficial circumflex iliac artery to the anterior superior iliac spine was (8.8±1.3) cm.The superficial circumflex iliac artery run to the anterior superior iliac spine and sent 1-3 periosteal branches into the iliac crest.The sartorius originates from the anterior superior iliac spine,and its proximal artery arises from the superficial circumflex iliac artery and the femoral artery.Link-pattern arterial anastomosises were formed in sartorius by branches of adja cent vascular pedicles,which nourished the ilium flap.All incisions healed by first intention.All cases were followedup from 16 to 42 months,with an average of 32.3 months.All fractures healed for 3-7 months,with an average of 4.6 months.No fracture nonunion,femoral head necrosis and other complications occurred.Harris hip scores was 93.02± 5.33.Seven cases were excellent and 4 cases were good.Conclusion The iliac flap pedicled with superficial cir cumflex iliac artery and sartorius has rich blood supply,easily performed conducive to promoting fracture healing,and reducing the occurrence of femoral head necrosis.It is an effective method for the treatment of femoral neck fracture in young adults.

Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.

OBJECTIVETo observe the regulative effects of the acupuncture on glucose and lipid metabolism disorder in the patients of metabolic syndrome.

METHODSSeventy-six patients of metabolic syndrome were rando-mized into an acupuncture plus western medicine group (37 cases) and a western medicine group (39 cases). In the western medicine group, the conventional western medication was used for 40 days. In the acupuncture plus western medicine group, the acupuncture was combined on the basis of the treatment as the western medicine group, the acupoints were Danzhong (CV 17), Zhongwan (CV 12), Tianshu (ST 25), etc. Ten treatments were as one session. There were 3 to 5 days of intervals between the sessions and totally 30 treatments were required. The body mass index (BMI), blood lipid, blood glucose, and comprehensive therapeutic effects were compared before and after treatment in the two groups.

RESULTSBefore and after treatment, the differences were all significant in BMI, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), plasma glucose of 2 hours post glucose-load (2 hPG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) (all<0.05) in the acupuncture plus western medicine group, and the results after treatment were superior to those before treatment; the difference was not significant in BMI (>0.05) and those were all significant statistically in TG, TC, LDL-C, HDL-C, FBG, 2 hPG, FINS, HOMA-IR (all<0.05) in the western medicine group, and the results after treatment were superior to those before treatment. After treatment, in comparison of the two groups, the results in the acupuncture plus western medicine group were better than those in the western medicine group. The differences were all signif-icant sta-tistically in BMI, TG, TC, LDL-C, HDL-C, FBG, 2 hPG, FINS, HOMA-IR (all<0.05).

CONCLUSIONSOn the basis of the conventional western medicine, the acupuncture relieves apparently the clinical symptoms and rectifies glucose and lipid metabolism disorder in the patients of metabolic syndrome.

Objective: To observe the effect of electroacupuncture (EA) on the electrogastrogram and gastric antrum ghrelin in rats with diabetic gastroparesis (DGP). Methods: Fifty Sprague-Dawley (SD) rats were randomly divided into group A, group B, group C, group D and group E, 10 rats in each group. Group A was the blank control group without intervention. Group B, Group C, Group D and Group E were treated with single dose intraperitoneal injection of 2% streptozotocin (STZ), combined with 8-week high glucose and high fat diet to establish DGP rat models. Group B was the model group without treatment. Group C was the EA at acupoint group, was treated with EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6). Group D was the EA at non-acupoint group, was treated by EA at the control points of Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6). Rats in the metoclopramide control group received 1.7% metoclopramide solution [10 mL/(kg·bw)] by gavage. Rat's blood glucose level was measured by blood glucose meter; gastric emptying rate was detected using phenol red as a marker; the electrogastrogram was detected by BL-420F biological function system; the protein level of ghrelin was detected by enzyme-linked immunosorbent assay (ELISA); the expression of ghrelin mRNA was detected by real-time polymerase chain reaction (RT-PCR). Results: Compared with group A, the blood glucose of group B, C, D and E were significantly increased before and after the treatment (all P<0.01); after treatment, the gastric emptying rate of group B was significantly decreased (P<0.01), the migration rates of small intestine in group B, C, D and E were significantly lower (all P<0.01), and the protein content of ghrelin in group C was significantly decreased (P<0.01); the expressions of ghrelin mRNA were significantly increased in group B, C, D and E (all P<0.01), the mean amplitudes of electrogastrogram in group B and D were significantly decreased (both P<0.01). After treatment, compared with group B, the blood glucose of group C was significantly decreased (P<0.05), the gastric emptying rate and small intestine migration rate were significantly increased in group C and E (P<0.05, P<0.01), the small intestinal migration rate was significantly increased in group D (P<0.05), the expression of ghrelin in protein and mRNA in group C was significantly lower (P<0.01), the expression of ghrelin mRNA in group E was significantly lower (P<0.05), and the mean amplitude of electrogastrogram in group C was significantly increased (P<0.05). After treatment, compared with group D, the protein and mRNA expressions of ghrelin in group C were significantly decreased (P<0.01). After treatment, compared with group E, the protein expression of ghrelin in group C was significantly decreased (P<0.01). Conclusion: EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) could regulate the blood glucose level of DGP model rats, enhance electrogastrogram activity, promote gastric emptying, and regulate ghrelin expression in protein and mRNA.

Objective: To observe the effect of electroacupuncture (EA) at Zusanli (ST 36) on the gastrointestinal motility and the ultrastructures of pacemaker cells [the interstitial cells of Cajal (ICC)] in diabetic gastroparesis (DGP) rats and explore the mechanism of EA for DGP.Methods: A total of 50 Sprague-Dawley (SD) rats were randomly divided into group A, group B, group C, group D and group E, with 10 rats in each group. Group A was the blank control; a single intraperitoneal injection of 2% streptozotocin (STZ) was performed in rats of group B, group C, group D and group E, with high glucose and high fat diet for 8 weeks to establish the DGP rat models. Group B was the model group and the rats did not receive any treatment; group C was EA at acupoint group and the rats received EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6); group D was EA at non-acupoint group and the rats received EA at the control points of Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6); group E was metoclopramide group and the rats were treated by intragastric administration of metoclopramide. Blood glucose was detected using ONE TOUCH blood glucose meter; gastric emptying rate and small intestine migration rate were measured using intragastric phenol red; ultrastructures of gastric antrum ICC were detected by transmission electron microscopy.Results: The differences of blood glucose between group B, group C, group D, group E versus that of group A were statistically significant after modeling (P<0.01); after treatment, the differences of blood glucose between group D, group E versus that of group C were statistically significant (P<0.05,P<0.01); the gastric emptying rate of rats in group B was statistically significant different from that in group A (P<0.01); the gastric emptying rate of rats in group C was statistically significant different from that in group B (P<0.01). The migration rates of rats' small intestines in group B, group C, group D and group E were all statistically significant different from that in group A (P<0.01); the migration rate of rats' small intestines in group C was statistically significant different from that in group B (P<0.01). The ultrastructure of rat's ICC in group B showed apoptosis compared with that in group A; rat's ICC in group C had complete basement membrane, more cytoplasm mitochondria, Golgi and rough endoplasmic reticulum, showing clear structure, occasional mitochondria swelling and gap junctions with adjacent smooth muscle cells; there were no significant differences between group D, group E versus group B.Conclusion: EA at Zusanli (ST 36) plus other acupoints can regulate the blood glucose and promote gastrointestinal motility in DGP rats, and the mechanism may be related to repairing the damaged ICC structure.