Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

Thoracoscopic mitral valve replacement is a common minimally invasive cardiac surgery procedure. However, small annulus, severe calcification of the annulus, and severe thickening of the posterior valve leaflet or sub valvular structure are the difficulties of thoracoscopic mitral valve replacement. Improper treatment can easily lead to left ventricular rupture or prosthesis-patient mismatch. This paper reports a thoracoscopic mitral bioprosthesis replacement case using the chimney technique in Guangdong Provincial People's Hospital and summarizes its operating key points. The patient was a 68-year-old female, weighing 36 kg. The preoperative diagnosis was rheumatic mitral stenosis and atrial fibrillation, the preoperative transthoracic echocardiogram showed the left ventricular end-diastolic diameter was 39 mm. The surgical effect was satisfactory. The patient was in good condition at the follow-up 2 months after the operation.

The small-molecule alkaloid halofuginone (HF) is obtained from febrifugine. Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions, which range from parasite infections and fibrosis to autoimmune diseases. In particular, HF is believed to play an excellent anticancer role by suppressing the proliferation, adhesion, metastasis, and invasion of cancers. This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF. In the studies covered in this review, the anticancer molecular mechanisms of HF mainly included transforming growth factor-β (TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2 (Nrf2), serine/threonine kinase proteins (Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated (Wnt)/β-catenin, the exosomal microRNA-31 (miR-31)/histone deacetylase 2 (HDAC2) signaling pathway, and the interaction of the extracellular matrix (ECM) and immune cells. Notably, HF, as a novel type of adenosine triphosphate (ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase (ProRS) and amino acid starvation therapy (AAS) to suppress the formation of ribosome, further exerts a significant effect on the tumor microenvironment (TME). Additionally, the combination of HF with other drugs or therapies obtained universal attention. Our results showed that HF has significant potential for clinical cancer treatment.

The small-molecule alkaloid halofuginone(HF)is obtained from febrifugine.Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions,which range from parasite infections and fibrosis to autoimmune diseases.In particular,HF is believed to play an excellent anticancer role by suppressing the proliferation,adhesion,metastasis,and invasion of cancers.This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF.In the studies covered in this review,the anticancer molecular mechanisms of HF mainly included transforming growth factor-β(TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2(Nrf2),serine/threonine kinase proteins(Akt)/mechanistic target of rapa-mycin complex 1(mTORC1)/wingless/integrated(Wnt)/β-catenin,the exosomal microRNA-31(miR-31)/histone deacetylase 2(HDAC2)signaling pathway,and the interaction of the extracellular matrix(ECM)and immune cells.Notably,HF,as a novel type of adenosine triphosphate(ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase(ProRS)and amino acid starvation therapy(AAS)to suppress the formation of ribosome,further exerts a significant effect on the tumor microenvironment(TME).Additionally,the combination of HF with other drugs or therapies obtained universal attention.Our results showed that HF has significant potential for clinical cancer treatment.

Objective:Investigating the efficacy of unilateral adrenalectomy in treatment for primary pigmented nodular adrenocortical disease (PPNAD).Methods:Clinical data of 26 patients with PPNAD treated in our hospital from January 2013 to June 2023 was retrospectively analyzed.There were 11 males and 15 females, with an average age of (19.4±4.7) years. 25 cases presented with typical Cushing's syndrome, and 16 cases were diagnosed with Carney's syndrome. PRKAR1A gene mutation detected in 8 out of 10 cases. CT showed multiple small nodules on bilateral adrenal glands in 14 cases, unilateral small nodules or mild thickening with normal contralateral glands in 8 cases, and no obvious abnormalities in 4 cases. All patients showed autonomous oversecretion of cortisol by endocrine laboratory tests, with a median 24 h-UFC of 408.35 (334.28, 800.78) μg/24 h and decreased level of adrenocorticotropic hormone. All 26 patients underwent laparoscopic unilateral adrenalectomy, with left side adrenalectomy in 8 cases and right side adrenalectomy in 18 cases.Results:The average surgical duration was (85.2±28.7) minutes, with intraoperative blood loss <50 ml in all cases. The median time to drainage tube removal post-operation was 3 (2, 3) days. One patient developed a postoperative pulmonary infection, and 3 patients required postoperative hormone replacement therapy. The median follow-up duration was 64 (31.5, 103.8) months, and all patients showed alleviation of Cushing syndrome clinical manifestations after operations. 19 patients (73.1%) had their 24 h-UFC levels normalized to a median of 42.0 (22.4, 58.3) μg/24 h within 8.5 (5, 46) days post-surgery. 7 patients (26.9%) did not achieve normal 24 h-UFC levels, yet experienced an average reduction of (73.2±10.4)%. 13 patients (50.0%) did not experience recurrence, with a median follow-up of 51 (7, 89.5) months, including two cases without recurrence at 10 years post-surgery. 13 patients showed recurrent increase in postoperative cortisol levels, with a median of 225.6 (188.9, 397.2) μg/24 h. The median time to increased 24 h-UFC post-surgery was 27 (13.5, 50.5) months, with the longest duration reaching 104 months. Among these, 9 cases exhibited clinical signs and symptoms of recurrence, while 4 cases did not. Of the 13 patients with recurrence, 9 underwent contralateral adrenalectomy or subtotal resection, while 4 were observed with follow-up.Conclusions:Unilateral adrenalectomy could be a surgical treatment option for PPNAD. Despite the recurrence in some patients postoperatively, unilateral adrenalectomy could effectively and rapidly reduce cortisol levels in PPNAD patients and alleviate the clinical manifestations of Cushing syndrome.

Objective:To investigate the differential expression of microRNA (miR)-214-3p in plasma exosomes in different types of uveal melanoma (UM) and evaluate whether miR-214-3p is a potential molecular biomarker for the diagnosis and prognosis of UM.Methods:Twenty-five UM in situ patients who received the enucleation of eyeball were enrolled at Beijing Tongren Hospital from December 2015 to October 2019, including 10 with epithelioid cell melanoma and 10 with spindle cell melanoma as well as 5 metastatic UM patients (1 with spindle cell-like melanoma and 4 with epithelioid cell-like melanoma) and 10 healthy subjects were enrolled during the same period.Blood sample was collected from all the subjects for the isolation of plasma exosomes.The morphology of exosomes was examined under the electron microscope.The exsomal marker proteins were identified by Western blot.The expression level of miR-214-3p in plasma exosomes was detected by real-time fluorescence quantitative PCR.The differential expression of miR-214-3p among different types of UM patients and healthy controls was compared.The diagnostic and classification performance of exosomal miR-214-3p was evaluated using receiver operating characteristic curve.Written informed consent was obtained from each subject prior to entering the study cohort.This study protocol was approved by an Ethics Committee of Capital Medical Univeristy (No.TRECKY2018-056).Results:The isolated exosomes were hemispherical in shape with a concavity on one side.The diameter of the exosomes was about 100 nm and the particle diameter of vesicles from samples was (82.0±2.7) nm.TSG101 protein was detectable and Calnexin protein was not found in the exosomes.The relative expression levels of plasma exosomal miR-214-3p in healthy control group, in situ UM group and metastatic UM group were 0.86(0.57, 1.49), 0.24(0.10, 0.67), and 0.43(0.23, 0.56), respectively.The miR-214-3p relative expression level in plasma exosomes of in situ UM patients and metastatic UM patients was significantly lower than that of healthy controls, and the differences were statistically significant ( Z=2.62, P<0.01; Z=2.08, P<0.05). The relative expression levels of exosomal miR-214-3p in spindle cell-like UM group and epithelioid cell-like UM group were 0.11(0.07, 0.64) and 0.46(0.14, 0.91), respectively, and no significant difference was found in the expression level of plasma exosomal miR-214-3p among different types of UM (all at P>0.05). The area under the curve of plasma exosomal miR-214-3p for UM diagnosis was 0.795. Conclusions:Plasma exosomal miR-214-3p level is significantly reduced in both in situ UM patients and metastatic UM patients.Plasma exosomal miR-214-3p is a new potential diagnostic biomarker for UM, but the exosomal miR-214-3p appears to not be able to distinguish the types of UM.

Major depression is a public health problem that seriously harms individuals and the society.But one of the major shortcomings of mainstream antidepressant is the delayed onset.Recent series of studies demonstrated that,from a variety of animal models and clinical studies,classic stagnation-removing formula Yue-Ju (Y J) pill has the advantage in rapid antidepressant efficacy,which is similar to the prototype drug ketamine.It has the mechanism of rapid and sustained enhancement of neural plasticity and individual difference in response to YJ pill.The evidence of Gardenia jasminoides (Zhi-Zi) as the monarch component of YJ pill's rapid antidepressant action has also been revealed.The further in-depth research on rapid antidepressant traditional Chinese medicine (TCM) is important for providing the scientific and reliable TCM strategies to treat depression.

Aim Using chronic pre-pregnancy stress to establish a postpartum depression animal model, given a single YG,and acute ketamine was served as control, to explore the pathology of PPD and the anti-depressive mechanism of the YG on the PPD model on AKT/mTOR signaling pathway. Methods Thirty-two fe-male Balb / c were randomly assigned to two groups, the control group ( Control, Con) and the pre-pregnancy stressed group(Model,Mod) , which was subjected to 3 weeks chronic restraint stress. After the last stressor, the pre-pregnancy stressed group was housed with a male. After about 4 weeks later, the mice gave birth to pups. Then at 3 weeks postpartum, we tested the ma-ternal tail suspension test ( TST). Both YG and Ket-amine was single administered 24 hours before behavior test, with single saline for control group and PPD mod-el group. After TST,the mouse hippocampus were ex-tracted to detect the expression of AKT and mTOR. Results After 3 weeks postpartum, the model mice showed depression-like behaviors. Immobility in TST was significantly increased in vehicle groups(P <0. 01). Acute YG improved performance in the TST (P< 0. 01), which was similar to ketamine. And the PPD model mice group showed decreased phosphorylation of AKT and mTOR (P < 0. 01,P < 0. 01), compared to control group. A single dose of YG or ketamine normal-ized AKT/ mTOR signaling in the PPD model mice(P< 0. 01,P < 0. 01),( P < 0. 01,P < 0. 01). Conclu-sions Chronic pre-pregnancy stress can induce dams into postpartum depression and its mechanism maybe associated with down-regulating AKT/ mTOR signa-ling. Acute YG exerts fast antidepressant effect on this PPD model similar to ketamine, and its mechanism may be related to up-regulating AKT/ mTOR signaling in the hippocampus.

Aim To observe the rapid antidepressant effect of Yuejuganmaidazao Decoction on postpatum de-pression offspring , and analyze its influence on the Akt and mTOR expression .Methods After postpartum de-pression model was established , the offsprings were randomly divided into the following groups: control group(CTL-F1,n =8), vehicle group (Veh,n =8) and YG group ( YG, n =8 ) .Veh group was treated with vehicle , YG group was treated with Yueju gan-maidazao Decoction(8.3 g· kg -1 ).Forced swimming test(FST) was measured 24 hours after single adminis-tration.The phosphorylation and total level of Akt and m-TOR in the hippocampus was detected by Western blot.Results The immobility time in YG group was significantly shorter than that in Veh group ( P <0.01 ) , and the expression of p-Akt and p-mTOR in the hippocampus was significantly increased ( P <0.05 ) .Conclusion Yuejuganmaidazao Decoction may rapidly alleviate depression-like behaviors of PPD offsprings through upregulation of Akt and mTOR ex-pression .

Abstact:Aim To identify whether the petroleum e-ther fraction of Yueju pill (YJ-PE)could exhibit a po-tent rapid antidepressant effect and to investigate the underlying biological mechanism involved.Methods Fourty-four male KM mice were randomly assigned to five groups:the control group (saline group),low dosage of YJ-PE,middle dosage of YJ-PE,high dos-age of YJ-PE and ketamine.After a single drug admin-istration,we used tail suspension test (TST)to test the rapid antidepressant effect of YJ-PE in KMmice at 30 min.Another twenty-four male KM mice were ass-inged to three groups:control group,screened effective low dosage of YJ-PE group and ketamine group.We usd TST to assess these mice at 24 h post a single ad-
ministration.Western blot was performed to examine the expression of BDNF and TrkB in hippocampus of KMmice at 30 min and 24 h post a single administra-tion.Results An acute administration of YJ-PE de-creased the immobility time of KMmice in TST and in-creased the expression of BDNF and TrkB as soon as 30min post a single administration and lasted at least for 24 hours.Conclusion YJ-PE (low dosage)ex-hibits a rapid antidepressant-like potent,and the po-tent rapid antidepressant effects of YJ-PE are associat-ed with the up-regulation of BDNF and TrkB.