Objective Alpha-1-acid glycoprotein （ORM） was a new target for the development of weight loss drugs. To search for potential weight loss drugs that could target ORM from the compound library of already marketed drugs based on drug repurposing. Methods The pGL4.20-ORM1 promoter recombinant plasmid was contructed and validated, and then a lentiviral vector was utilized to establish stable AML12 cell lines expressing ORM1 promoter-LUC-PURO. This cell line was employed for high-throughput screening of compounds from the marketed drug library, and the luminescence value of the cells was characterized by enzyme marker. Results Primary screening and secondary screening of 1 470 compounds identified 42 compounds that increased ORM1 promoter expression and could be used for further weight loss effect assessment. Conclusion This study successfully constructed LV-AML12-ORM1 promoter-LUC-PURO stable expression cell lines using lentiviral vectors, laying a foundation for efficient and stable screening of weight loss drugs targeting ORM.

Objective To calculate the absorbed doses and conversion coefficients of various organs in humans after oral administration of urea-¹⁴C, and to provide a convenient method for evaluating the internal radiation dose caused by ingestion of urea-¹⁴C in Chinese population. Methods The Chinese reference human voxel model was imported into the FLUKA software to simulate the absorbed doses to organs under internal exposure to ¹⁴C, and to obtain the dose conversion coefficients for oral administration of urea-¹⁴C. Results The absorbed dose conversion coefficients for the stomach, colon, bladder, heart, and muscles were 0.029, 0.029, 0.32 (0.24), 0.028, and 0.029 mGy/MBq in negative cases, and 0.079, 0.078, 0.18 (0.15), 0.076, and 0.080 mGy/MBq in positive cases. The committed effective dose coefficients were 0.041 (0.037) mSv/MBq in negative cases and 0.082 (0.081) mSv/MBq in positive cases. Conclusion The dose conversion coefficients obtained in this study can provide important parameters for evaluating the absorbed dose to Chinese population after oral administration of urea-¹⁴C.

Objective To investigate the effect of intensive phototherapy for neonatal hyperbilirubinemia on cellular immune function and short-term immune-related adverse effects.Methods Totally 180 infants with hyperbilirubi-nemia were treated with different light intensity,the efficacy,cellular immune function and immune adverse effects were followed up for six months after discharge.Results After phototherapy,serum interleukin-6(IL-6)in both groups were decreased and CD4+(%)and CD4+/CD8+were increased than that before phototherapy.The decrease rate of total bilirubin in the intensive phototherapy group was significantly faster than that in the conventional photo-therapy group,at the same time,the total duration of phototherapy and hospital stay were significantly shorter than that in the conventional phototherapy group(P＜0.05).No statistical significance in the incidence of diarrhea,rash,fever and hypo-calcemia during hospitalization and no immune-related adverse effects in 6 months after discharge were recorded.Conclusions Compared with conventional phototherapy,intensive phototherapy reduces serum bilirubin level more quickly and shorten the duration of phototherapy and hospital stay.No common adverse effects nor immune-related adverse effects are recorded during hospitalization and the period of six months after discharge.

Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)％vs.1.62(3.50)％],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P＜0.05 or＜0.01).There were no significant difference in LVEDd and LVEF between two groups,P＞0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.

Polyunsaturated fatty acids (PUFAs) have diverse health-promoting effects, such as potentially protecting in immune, nervous, and cardiovascular systems by targeting a variety of sites, including most ion channels. Voltage-gated potassium channels of the K_V7 family and large-conductance Ca²⁺- and voltage-activated K⁺ (BK_Ca) channels are expressed in many tissues, therefore, their physiological importance is evident from the various disorders linked to dysfunctional K_V7 channels and BK_Ca channels. Thus, it is extremely important to learn how potassium channels are regulated by PUFAs. The aim of this review is to provide an overview of the effects of PUFAs on K_V7 channels and BK_Ca channels functions, as well as the mechanisms underlying these effects. In summarizing reported effects of PUFAs on K_V7 and BK_Ca channels mediated currents, we generally conclude that PUFAs increase the current amplitude, meanwhile, differential molecular and biophysical mechanisms are associated with the current increase. In K_V7 channels the currents increasement are associated with a shift in the voltage dependence of channel opening and increased maximum conductance in K_V7 channels, while in BK_Ca channels, they are associated with destabilization the pore domain closed conformation. Furthermore, PUFA effects are influenced by auxiliary subunits of K_V7 and BK_Ca channels, associate with channels in certain tissues. although findings are conflicting. A better understanding of how PUFAs regulate K_V7 and BK_Ca channels may offer insight into their physiological regulation and may lead to new therapeutic strategies and approaches.

Objective To investigate the therapeutic effect of cnithol on acute pancreatitis(AP)rats and its regulatory mechanism on phosphoinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods SPF-grade SD male rats were randomly divided into control group,model group(50 μg·kg-1 hyranin+10 mg·kg-1 LPS),positive control group(2 mg·kg-1 dexamethasone),experimental-L group(20 mg·kg-1 osthol)and experimental-H group(40 mg·kg-1 osthol),experimental-H+740Y-P group(40 mg·kg-1 osthol+2 mg·kg-1 PI3K activator 740Y-P),15 mice in each group.The activities of amylase and lipase in serum of rats were detected by automatic biochemical analyzer 24 h after the last administration.The levels of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum,the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in pancreas were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of pancreatic tissue and score the pathological damage.Western blot was used to detect the expression of PI3K/Akt pathway related proteins in rat pancreas.Results The activities of serum amylase in control group,model group,positive control group,experimental-H group and experimental-H+740Y-P group were(135.67±12.89),(1 027.84±32.16),(174.31±15.27),(186.70±17.39)and(835.92±28.78)U·mL-1,respectively;the contents of TNF-α were(35.69±3.10),(223.54±15.23),(48.76±4.25),(52.31±4.68)and(208.46±13.65)pg·mL-1,respectively;the contents of MDA were(2.15±0.14),(6.37±0.42),(2.78±0.17),(2.81±0.15)and(5.96±0.36)nmol·mg-1,respectively;the histopathological injury scores were 1.12±0.07,10.23±0.38,3.14±0.21,3.25±0.23 and 9.68±0.40,respectively;p-PI3K/PI3K ratios were 0.82±0.05,1.96±0.15,1.07±0.06,1.10±0.07 and 1.69±0.14,respectively.The above indexes were compared with the control group in the model group,the positive control group,experimental-H group and the model group,and the above indexes of experimental-H+740Y-P group and experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion Gossetin can play a therapeutic role in AP,and its mechanism may be related to the inhibition of PI3K/Akt signaling pathway.

Objective To investigate the protective effect of dexmedetomidine(Dex)pretreatment on myocardial ischemia-reperfusion mice and the effect of Nod-like receptor protein 3(NLRP3)inflammatory signaling pathway.Methods C57BL/6J mice were randomly divided into sham group(only threading without ligation),model group(recovery after ligation of left anterior descending coronary artery),positive group(modeling after intraperitoneal injection of 1 mg·kg-1 trimetazidine),Dex group(modeling after intraperitoneal injection of 20 μg·kg-1 dexmedetomidine),MCC950 group(modeling after intraperitoneal injection of 10 mg·kg-1 NLRP3 inhibitor MCC950),12 mice in each group.Cardiac function indexes were detected at 24 h after reperfusion,the expression level of related proteins in myocardial tissue was detected by Western blot,enzyme-linked immunosorbent assay(ELISA)was used to detect the expression level of serum factor,myocardial antioxidant index was detected by kit method,and apoptosis was detected by Tunel method.Results The NLRP3 protein expression levels of sham group,model group,positive group,Dex group and MCC950 group were 0.31±0.05,1.06±0.07,0.52±0.05,0.65±0.07 and 0.39±0.04,respectively;the expression levels of apoptosis-associated granuloid protein(ASC)were 0.27±0.08,0.88±0.09,0.46±0.05,0.59±0.07 and 0.34±0.04,respectively;CK-MB levels were(25.64±2.94),(102.08±7.04),(49.61±7.70),(60.86±5.24)and(63.24±5.38)U·L-1,respectively;IL-6 levels were(104.78±10.73),(231.54±15.56),(158.20±16.54),(165.10±14.77)and(141.17±14.08)pg·mL-1,respectively;Tunel positive cell rates were(4.34±0.16)％,(25.98±1.58)％,(8.74±0.93)％,(11.06±1.07)％and(9.19±0.88)％,respectively.Sham group were compared with model group;Dex group and MCC950 group were compared with model group,the above indexes were statistically significant(all P＜0.05).Conclusion Dexmedetomidine preconditioning may prevent ischemia-reperfusion myocardial injury by inhibiting NLRP3/ASC/caspase-1 inflammatory pathway,inflammatory response and myocardial cell apoptosis.