Hepatocellular carcinoma is one of the most common cancers and causes of cancer-related death in the world, the insidious onset, rapid progression and poor prognosis make the treatment more difficult. At present, the current therapeutic options, include surgical resection, ablation, postoperative recurrenceare still with disadvantages. The efficacy of targeted drug therapy is also unsatisfactory. Immunotherapy is a promising research direction. Immunosuppressants at the molecular level have shown initial success, while adoptive immunocell therapy at the cellular level has also shown promising results, the typical example is chimeric antigen receptor cell therapy. The purpose of this review is to summarize the recent research progress on chimeric antigen receptor cellular therapy in liver cancer.

Objective:To investigate the value and influence factors of preoperative and intraoperative localization of ectopic hyperparathyroidism (EHPT).Methods:Results of 99mTc-sestamibi ( 99mTc-MIBI), neck ultrasound, contrast CT and intraoperative local venous parathyroid hormone (IOLVPTH) were retrospectively analyzed in 205 patients with primary hyperparathyroidism (PHPT) suspected of EHPT. Results:Incidence of EHPT was 16.6% (34 cases), and 36 ectopic lesions were detected. The proportion of EHPT in antero-superior mediastinum, intrathyroidal, in the retropharyngeal region, in carotid sheath, in the prevertebral region and intrapericardial were 44.1% (15 cases), 29.4% (10 cases), 11.8% (4 cases), 5.9% (2 cases), 5.9% (2 cases) and 2.9% (1 cases), respectively. Contrast CT was the most sensitive (86.1%, 31 lesions/36 lesions) for EHPT, followed by 99mTc-MIBI (66.7%, 24 lesions/36 lesions), IOLVPTH monitoring (61.8%, 21 lesions/34 lesions) and neck ultrasound (55.6%, 20 lesions/36 lesions). Contrast CT was most sensitive,100% in detecting deep-located EHPT lesions, whereas IOLVPTH had advantages in detecting intrathyroidal EHPT lesions, with a sensitivity of 100.0%.The combined use of 99mTc-MIBI and neck ultrasound showed a sensitivity of 77.8% in the localization of EHPT. Conclusions:Contrast CT is highly sensitive in the localization of EHPT. The combined use of preoperative imaging and IOLVPTH monitoring helps to higher localization for EHPT.

Objective:To assess possible risk factors and their respective levels in the whole process of investigator initiated trial(IIT)projects proposed in the proposal stage, for reference in formulation of risk management plans.Methods:Through literature analysis and research group discussions, the risk factors of IIT projects and risk level assessment criteria were preliminarily identified, and a consultation questionnaire was developed as a result. Delphi method was used to further optimize the risk factors and determine their risk levels. Data obtained from the consulfation were analysied by descriptive.Results:The recovery rates of two rounds of expert consultation were both 100%, and the degree of expert authority was 0.942. The survey finalized 38 risk factors, including extremely high risk, high risk, medium risk, low risk and very low risk factors of 17(44.7%), 15(39.5%), 3(7.9%), 2(5.3%) and 1(2.6%) respectively.Conclusions:This study determined a risk evaluation system of IIT projects in the proposal stage. This system can identify risks of IIT projects at an early stage, facilitating early intervention of problems existing in such projects, and minimize risks to the rights and safety of patients.

Effective supervision of the clinical research management department can guarantee and improve the quality of the investigator initiated trials(IIT). The authors analyzed relevant clinical research regulations and literature and summarized the current situation of risk-based IIT project process quality management. On such basis, they determined the risk-based IIT project process quality management method in combination with the previous research of the research group.From 2021 to 2022, this method was used to implement process quality management for 353 IIT projects in Shanghai′s tertiary hospitals. More than 3 000 risk points were identified through centralized supervision, and then on-site supervision was carried out to correct the problems found. As proven by the results, the method could find existing problems in time and define the risk level of the project, and also formulate an individualized risk supervision plan accordingly, so as to effectively ensure the data reliability and scientific results. It is suggested that the clinical research management department implement risk based management for the whole process of IIT projects, increase funding and staffing, and implement hierarchical management for the projects by research types, so as to promote the sustainable development of IITs.

Objective To observe the changes and significance of the protein expression levels of nuclear factor-κB p65 (NF-κB p65), transforming long factor-β1 (TGF-β1) and apoptosis-related factors Bcl-2 and Bax in myocardial tissue of Bama miniature pig model of diabetic cardiomyopathy (DCM). Methods Ten healthy male Guangxi Bama miniature pigs, aged 4 to 5 months old, were selected and divided into control group and model group according to the random number table method, with 5 pigs in each group. After 12 hours of fasting in the two groups, the DCM model was replicated by intravenous injection of streptozotocin (STZ) 150 mg/kg; for the Bama miniature pigs in the control group, citric acid-sodium citrate buffer 150 mg/kg was injected intravenously. After 10 months of modeling, the basic conditions of the two groups of animals were observed and their fasting blood glucose (FPG) levels were detected. The protein expression levels of NF-κB p65, TGF-β1, Bcl-2 and Bax in myocardial tissue of two groups were detected by Western Blot and the pathological changes of myocardial tissue were observed under electron microscope. Results In the model group, 4 models were successfully established, and 1 died. The model pigs had symptoms such as polydipsia, polyphagia, polyuria and decreased body weight. The FPG level in the model group was significantly higher than that in the control group (mmol/L: 25.53±3.75 vs. 4.68±0.77, P < 0.01). Compared with the control group, the protein expression levels of NF-κB p65, Bax and TGF-β1 in the myocardial tissue of model group were significantly increased (NF-κB p65/GAPDH: 0.46±0.05 vs. 0.38±0.02, Bax/GAPDH: 0.46±0.01 vs. 0.35±0.01, TGF-β1/GAPDH: 0.39±0.01 vs. 0.33±0.01, all P < 0.05) and the expression level of Bcl-2 protein was significantly decreased (Bcl-2/GAPDH: 0.33±0.01 vs. 0.42±0.01, P < 0.01). Electron microscopy results showed that the myofibrils of myocardial tissue in the DCM model group were disordered, and the number of mitochondria in the gap was significantly reduced. A large number of mitochondria with vacuolar degeneration were observed. Conclusions The DCM model of Bama miniature pigs can be successfully replicated after 10 months of high-dose STZ disposable ear vein injection. The DCM model miniature pigs have obvious glucose metabolism disorder, and their myocardial tissue has inflammatory reaction, cardiomyocyte apoptosis and fibrosis.

OBJECTIVETo dynamically observe the effects of electroacupuncture (EA) on repair of gastric mucosal lesion in rats with gastric ulcer, and to explore the time-effect relationship and molecular mechanism of EA for gastric ulcer.

METHODSA total of 72 SD rats were randomly assigned to a normal group, a model group, a acupoint group and a sham acupoint group, and each group were further divided into a 1-day subgroup, a 4-day subgroup and a 7-day subgroup, 6 rats in each subgroup. The rat model of gastric ulcer was established by using intragastric administration of ethyl alcohol. The rats in the acupoint group were treated with EA at"Zusanli"(ST 36) and"Liangmen"(ST 21); the rats in the sham acupoint group were treated with EA at points 5 mm next to"Zusanli"(ST 36) and"Liangmen"(ST 21); the EA was given 30 min per treatment, once a day. The rats in the normal group and model group were treated with immobilization for 30 min per day, and no EA was given. PR-PCR method was applied to test the expression of proliferating cell nuclear antigen (PCNA) and substance P (SP); Western blot method was applied to test the expression of neurotensin (NT).

RESULTSAfter 1-day treatment, the ulcer index in the model group was higher than that in the normal group (<0.01), and the expression of PCNA, SP and NT was decreased (<0.01, <0.05); compared with the model group and sham acupoint group, the ulcer index was decreased in the acupoint group (both <0.05), and the expression of PCNA and SP was up-regulated (all <0.05) while that of NT was up-regulated (both <0.01). After 4-day treatment, the ulcer index in the model group was reduced but still higher than that in the normal group (<0.05), and the expression of PCNA, SP and NT was up-regulated and higher than that in the normal group (all <0.01); the ulcer index in the acupoint group was similar to that in the normal group (>0.05), and the expression of PCNA and SP was lower than that in the model group (<0.01, <0.05), and the expression of NT was not significantly different from that in the model group (>0.05). After 7-day treatment, the differences of indexes above were not significant among the four groups (all >0.05).

CONCLUSIONEA at acupoints of stomach meridian has two-way regulation on PCNA and SP and improve the expression of NT in different pathological state of gastric ulcer, which could further improve the repair of gastric ulcer.

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.