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.

The new business forms are the new patterns of the job market extended by the use of mobile internet, big data, cloud computing, and other information technologies in the context of a new round of information technology development. In recent years, under the catalysis of the new employment model, a large number of new business employees have emerged such as food delivery riders, couriers, and online car-hailing drivers, whose employment forms are flexible and don’t fully conform to the establishment of labor relations with the employers, and whose problem of overtime work is common. The employment characteristics of new business forms of "focusing on performance and ignoring responsibility" make workers at great risks of occupational injuries and occupational health problems such as work-related musculoskeletal disorders, mental disorders, and overwork. However, the current research on occupational safety and health of workers in new business forms is insufficient, and the experience of institutional practice and supervision is also limited. Therefore, based on relevant research progress at home and abroad, this paper discussed the health injuries of workers in new business forms, summarized associated influencing factors from four aspects: employment form, employment affiliation, long working hours exposure, and institutional guarantee, and then proposed countermeasures to strengthen occupational safety and health protection of workers. For the current problems in the employment of new business forms, the government, enterprises, and workers need to work together to improve the legal and regulatory system for employment of new business forms, and standardize occupational safety and health management, thus effectively protect the occupational safety and health rights and interests of workers in new business forms.

Objective:To investigate the effect of dexmedetomidine-based anesthesia on gastrointestinal function in the patients undergoing laparoscopic radical resection for colorectal cancer.Methods:One hundred patients, aged 40-70 yr, with body mass index of 18-29 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ to Ⅲ, scheduled for elective laparoscopic radical resection for colorectal cancer, were divided into 2 groups ( n=50 each) using a random number table method: dexmedetomidine group (group D) and control group (group C). In group D, dexmedetomidine was intravenously infused as a bolus of 0.5 μg/kg at 10 min before anesthesia induction, followed by a continuous infusion of 0.5 μg·kg - 1·h - 1 until the end of surgery. In group C, the equal volume of normal saline was administered at the same time points. Patient-controlled intravenous analgesia was performed with hydromorphone, flurbiprofen, and metoclopramide after operation. Oxycodone was taken orally for rescue analgesia when visual analog scale score> 3. Serum intestinal fatty acid-binding protein concentrations were determined using an enzyme-linked immunosorbent assay at 10 min before anesthesia induction (T 1), 10 min after establishing pneumoperitoneum (T 2), immediately after tumor resection (T 3), 30 min before the end of surgery (T 4), and 1 h after the end of surgery (T 5). Gastrointestinal function was assessed using the I-FEED scoring system at 1-6 days after surgery.The intraoperative consumption of propofol and remifentanil, time to first flatus, first defecation and first oral intake and duration of hospital stay after surgery, and requirement for rescue analgesia within 3 days after surgery were recorded. Results:Compared with group C, the serum intestinal fatty acid-binding protein concentrations were significantly decreased at T 3-T 5, the I-FEED scores were decreased on postoperative days 3-5, the intraoperative consumption of propofol and remifentanil was decreased, and the time to first flatus, first defecation and first oral intake and duration of hospital stay were shortened ( P<0.05), and no significant difference was found in the rate of rescue analgesia in group D ( P>0.05). Conclusions:Dexmedetomidine-based anesthesia can promote the recovery of postoperative gastrointestinal function in the patients undergoing laparoscopic radical resection for colorectal cancer.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of polyisobutylene （PIB）-type Gutong plaster （called “PIB Gutong plaster” for short） versus non-steroidal anti-inflammatory drugs （NSAIDs） in the treatment of osteoarthritis in Chinese adults. METHODS Based on a real-world study， after propensity score matching， the decrease in pain visual simulation score， utility increase， time to pain resolution， time to return to normal range of motion and total adverse events of PIB Gutong plaster versus three NSAIDs （celecoxib， diclofenac sodium， and ibuprofen） were evaluated. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of patients using PIB Gutong plaster versus the three NSAIDs from the perspective of the whole society， and sensitivity analysis was carried out. RESULTS In terms of effectiveness， the recovery time of joint activity in PIB Gutong plaster group was significantly longer than that in celecoxib group， the decrease in VAS score of PIB Gutong plaster was significantly higher than that of ibuprofen but significantly lower than that of diclofenac sodium； the time of pain disappearance was longer than that in diclofenac sodium group and ibuprofen group， and the increase in health utility was significantly lower than that in diclofenac sodium group （P＜0.05）. In terms of safety， there were no significant differences in the incidence and severity of adverse events of PIB Gutong plaster， compared with the three NSAIDs， without statistical significance （P＜0.05）. In terms of cost-effectiveness， compared with celecoxib and diclofenac sodium， PIB Gutong plaster was dominant. Compared with ibuprofen， the ICER value of PIB Gutong plaster was 178 611.58 yuan/QALY， indicating that at the current price， PIB Gutong plaster was cost-effective if the threshold was 3 times GDP per capita. The results of sensitivity analysis were consistent with those of basic analysis. CONCLUSIONS The efficacy of PIB Gutong plaster was better than that of ibuprofen， similar to that of celecoxib， but worse than that of diclofenac sodium， the safety was consistent with the three NSAIDs， and the cost-effectiveness of PIB Gutong plaster needs to be improved.

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

OBJECTIVE To evaluate the econo mical efficiency of Recombinant human thrombopoietin injection （called “rhTPO”for short ）versus Etrapopa ethanolamine tablets （called“Etrapopa”for short ）in the second-line treatment of primary immune thrombocytopenia （ITP）in the Chinese adult patients. METHODS Based on the decision tree-embedded Markov model with a 4-week cycle ，the cost and utility related to bleeding events and adverse events after the use of the two drugs were measured and compared from the perspective of Chinese health system. The horizon was 12 weeks，and the cost and health outcome were not discounted. RESULTS Compared with Etrapopa ，rhTPO improved the quality adjusted life year by 0.002 5 and reduced the cost by 1 824.36 yuan，which was the absolute advantage scheme. Univariate sensitivity analysis showed that the base results were greatly affected by the dosage of rhTPO and Etrapopa during maintainance period. In most cases ，rhTPO was economical. Probability sensitivity analysis showed that when willingness-to-pay threshold varied between 0 yuan and 250 000 yuan，the probability about that rhTPO was economical ranges from 99.90％ to 100％. CONCLUSIONS Based on the available evidence ，rhTPO is more economical in the short term than Etrapopa in the second-line treatment of ITP.

Objective:To investigate the efficacy of recapping laminoplasty preserving the continuity of superior spinous ligament in the treatment of benign tumors in the lumbar spinal canal.Methods:A retrospective analysis was performed. The clinical data of 23 patients with benign tumors in lumbar spinal canal, admitted to our hospital from March 2018 to March 2020, were collected. Follow up was performed for 12-23 months; Japanese Orthopaedic Association (JOA) scores were used for efficacy evaluation. X-ray, CT and MRI were used for imaging evaluation.Results:The number of replanted lamina was 1-4, with an average of 2.2. The surgical duration was (77.2±22.7) min, ranged from 67 min to 146 min; and the amount of intraoperative bleeding was (127±32.6) mL, ranged from 90-290 mL. The tumors were completely removed in all patients, and there were 2 patients complicated with cerebrospinal fluid leakage, and the wound healed after electrolyte supplement and local pressure treatment. No spinal cord injury, epidural hematoma, infection or other related complications were noted. The JOA scores increased from 11.85±1.38 before surgery to 23.22±2.47 at the last follow-up, with significant difference ( t=18.505, P<0.001). Of them, 10 had excellent efficacy, 9 had good efficacy, and 4 had medium efficacy, enjoying an excellent and good rate of 82.6%. Lumbar lordosis angle (LLA) was (51.58±2.39)°at the last follow-up, which showed no significant difference as compared with the preoperative LLA ([52.24±3.17]°, t=0.672, P=0.505). Imaging results showed that there was no spondylolisthesis or instability of lumbar spine, no recurrence of tumors was noted, and no displacement of lamina or secondary reduction of spinal canal volume were noted. Conclusion:The treatment of benign tumors in lumbar spinal canal by modified recapping laminoplasty preserving the continuity of superior spinous ligament can restore the normal anatomical structure of lumbar spinal canal, achieve no bone loss and maintain lumbar curvature well.

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.

Rehabilitation medicine is one of the most important specialties in community health institutions. This article introduces the 12 year′s development of rehabilitation medicine in Fenglin Community Health Service Center, focusing on the talent allocation, service capabilities, resource expansion, basic facilities, personnel recruiting, department operating, service scope, and its achievements and influence, to provide reference for planning and construction of featured specialty in community health service centers.

Community health institutions have entered a new development stage of featured specialty construction. After 12 years of development, rehabilitation medicine now is the featured specialty of Fenglin Community Health Service Center. This article presents the train of thought and key points of specialty construction in primary care institutions based on the Fenglin′s experience. The positioning of featured specialty should be based on the community. The construction process should include 7 elements, namely, the standard operation procedure(SOP)of service system construction, the detailed publicity and implementation of the collaboration of specialists, prevention and control knowledge promotion for general practitioners, prevention and control knowledge education for community residents, service list, clinical efficacy evaluation, and clinical database. In the later iterations, the head of the department should always focus on the service system construction SOP and clinical database construction, and the rest parts can be assigned to the relevant team members.