Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Left ventricular assist device (LVAD) serves as a critical therapeutic option for patients with end-stage heart failure, significantly enhancing survival rates and quality of life. However, LVAD implantation exerts complex and profound effects on right ventricular (RV) function, with RV dysfunction emerging as a key factor influencing the prognosis of LVAD patients. This article systematically reviews the relationship between LVAD and RV function, exploring the importance of RV function in LVAD patients, assessment methods, underlying mechanisms of impact, and strategies for prevention and management. Comprehensive evidence suggests that preoperative evaluation of RV function is crucial for predicting the risk of RV dysfunction, while effective prevention and management rely on preoperative optimization, meticulous intraoperative techniques, rigorous postoperative monitoring, and multidisciplinary collaboration. Furthermore, this review discusses the potential and future directions of emerging technologies, such as improved LVAD designs, biventricular assist devices, gene therapy, and personalized medicine, in ameliorating RV dysfunction. In conclusion, RV function is one of the key determinants of successful LVAD therapy. Through comprehensive assessment, prevention, and management of RV function, coupled with the application of novel technologies, the clinical outcomes of LVAD patients can be further improved.

The incidence of psycho-cardiological diseases， i.e.， cardiovascular diseases combined with psychological disorders， is increasing year by year. Brain-derived neurotrophic factor （BDNF） plays a role in the pathogenesis of such diseases. According to the theory of collateral diseases， our team innovates the concept of regulating mental activity by dredging collaterals in the treatment of psycho-cardiological diseases and summarizes the concepts of "heart of Qi and collaterals" and "heart of vessels and collaterals". We believe that obstructed collaterals and disturbed mental activity run through the whole course of psycho-cardiological diseases， being the core pathogenesis. BDNF closely related to the core pathogenesis can regulate nerve and vascular inflammation， alleviate oxidative stress， and mediate a variety of signaling pathways， thereby promoting the survival and repair of nerve cells and vascular endothelial cells to regulate emotion and protect the heart. Therefore， BDNF is one of the potential biomarkers for clinical treatment of psycho-cardiological diseases. Collateral obstruction caused by blood stasis is specifically manifested as collateral deficiency， blood stasis， and Qi stagnation in collaterals. It can easily lead to inflammation， free radical generation， and antioxidant system changes in the patients with psycho-cardiological diseases， which can cause oxidative stress damage， affect the BDNF level， and result in mental disorders， such as anxiety and depression. Disturbed mental activity is mainly caused by the disturbance in the heart of Qi and collaterals， which is specifically manifested as the disturbance of the mind and liver soul. It is prone to cause anxiety or depression symptoms， which is closely related to the BDNF-mediated abnormal activation of neural circuits， nerve injury， and inflammation. This article elaborates on the theoretical connotation and pathological mechanism of regulating mental activity by dredging collaterals in the treatment of psycho-cardiological diseases from the perspective of BDNF， aiming to provide new ideas for the prevention and treatment of psycho-cardiological diseases and collateral diseases.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective:To explore the association rules of personality traits and health-promoting lifestyle in patients with primary angle closure glaucoma, so as to provide advice for the synthetical treatment.Methods:From July to November 2021, a total of 117 primary angle closure glaucoma patients(acute patients n=89, chronic patients n=28) in ophthalmology department of five hospitals in Nanjing were investigated with type A behavior pattern scale, health-promoting lifestyle scale Ⅱ and general information questionnaire.Based on Weka 3.8.5, algorithm of Apriori was used to mine its association relationship. Results:(1) The total scores of type A behavior pattern scale for patients with acute and chronic types of primary angle closure glaucoma were (32.48±6.43) and (27.54±6.49) respectively.The total scores of health-promoting lifestyle scale Ⅱ were (101.69±11.83) and (97.79±7.78) respectively.(2) There were positive associations among patients with acute primary angle closure glaucoma, type A/A-personality (including impatience and hostility) and health-promoting lifestyle (including stress management disorder, interpersonal relationship management disorder, well sense of health responsibility and adequate dietary nutrition intake)(all support>0.1, confidence >0.6, lift >1.0). And patients with chronic primary angle closure glaucoma were associated with B/B-personality (including patience and mild), health-promoting lifestyle (including stress management disorder, interpersonal relationship management disorder, well sense of health responsibility and adequate dietary nutrition intake)(all support>0.1, confidence >0.6, lift >1.0).Conclusion:Primary angle closure glaucoma is strongly related with personality traits and health-promoting lifestyle.Its synthetical treatment plan should take both physical and mental measures, and classified health management for patients with different disease types.

Objective:To evaluate the clinical effect of the pulmonary rehabilitation system based on the concept of prehabilitation for patients after cardiac surgery to wean tube and avoid related complications.Methods:From January 2018 to December 2019 in a single-center(third-class hospital in cardiac surgery intensive care unit), all adult patients hospitalized for 7 days before open-heart surgery were included. They were randomly divided into pulmonary rehabilitation group(198 cases) and control group(234 cases). To compare and analyze the clinical effects, the main observations were observed including overall outcome indicators(such as early extubation rate, ICU stay, hospitalization costs, advanced oxygen therapy support after extubation) and lung outcome related indicators(such as the occurrence of pulmonary complications, chest drainage, secondary intubation, tracheotomy, lung infection and chest tube drainage).Results:There was no statistical difference between groups in basic conditions and surgical conditions. The lung rehabilitation group significantly increased the rate of early extubation, reduced the number of advanced oxygen therapy after weaning, shortened the length of ICU stay, saved hospitalization cost, significantly reduced the occurrence of postoperative respiratory complications and improved postoperative respiratory function( P<0.05). Conclusion:During cardiac perioperation, pulmonary rehabilitation significantly can increase the rate of early extubation , shorten the length of mechanical ventilation, reduce the occurrence of secondary tracheal intubation and pulmonary complications. And it can also effectively promote the recovery of lung function and the overall recovery.

Objective To explore the relation of gamma knife radiation doses and changes of trigeminal nerves after gamma knife irradiation by studying the changes of trigeminal somatosensory evoked potentials (TSEP) characteristics oftrigeminal nerve roots irradiated by gamma knife in normal animals.Methods Fifteen New Zealand rabbits were divided into 60 Gy irradiation group,80 Gy irradiation group,100 Gy irradiation group,120 Gy irradiation group and control group in accordance with random number table (n=3).The first 4 groups used Gamma Plan 5.34 planning system to design the radiation targets and radiation doses.The target was placed at trigeminal nerve root entry zone,bilateral irradiation was performed,and the central dose was divided into 60 Gy,80 Gy,100 Gy and 120 Gy.The bilateral TSEP was monitored before and 6 months after irradiation.The monitoring data were recorded and statistical analysis was performed.Results P1,N1,P2 wave latencies,P1-N1,N1-P2 interpeak latencies and amplitudes in the 60 Gy irradiation group after irradiation showed no significant differences as compared with those in the control group (P＞0.05);P1,N1,P2 wave latencies,P1-N1,N1-P2 interpeak latencies and amplitudes in the 80 Gy irradiation group,100 Gy irradiation group,and 120 Gy irradiation group after irradiation showed significant differences as compared with those in the control group (P＜0.05),and these changes increase with increase of doses.Conclusion The changes of TSEP,which increase with increase of doses,are closely related to the doses of gamma knife irradiation,of which 80 Gy is the lowest dose to produce changes.

Objective:To explore expression of miR-146b in peripheral blood serum and aortic wall tissues in patients with acute Stanford type A aortic dissection (TAAD),and to discuss the significance and underlying mechanisms.Methods:The subjects were divided into a control group (excluded relative aortic diseases) (n=23) and a TAAD group (n=27).The miR-146b levels of serum and aortic wall tissues were detected by quantitative real-time PCR (qRT-PCR).Serum miR-146b and aortic wall tissues miR-146b were compared among different risk TAAD groups.The correlations between miR-146b and severity of aortic dissection were analyzed.MiR-146b related target genes were predicted by the DIANA LAB-TarBase 6.0 and TargetScan.Results:The expression levels of miR-146b in the serum and aortic wall tissues in the TAAD group were significantly elevated compared with those in the control group (P＜0.001).Compared with the mild risk group,the miR-146b levels of serum and aortic wall tissues were significantly higher in the moderate risk and severe risk groups (P＜0.05).The expression of miR-146b was positively correlated with the risk severity of TAAD patients (r=0.862,0.872;P＜0.05).Nuclear factor kappa B1 (NF-κB1),tumor necrosis factor receptor-associated factor 6 (TRAF6),matrix metalloproteinase 16 (MMP16) and actin alpha 2 (ACTA2) were miR-146b related target genes.Conclusion:The upregulation of miR-146b in peripheral blood serum and aortic wall tissues may contribute to the pathogenesis of TAAD and the severity of this disease.

Objective To observe the clinical application effects of Disposcope endoscope in Univent tube intubation and positioning.Methods Eighty patients underwent scheduled thoracic sur gery (51 males,29 females,aged 18-77 years,ASA Ⅰ-Ⅲ) under one-lung ventilation (OLV) were randomly grouped into two groups:Disposcope endoscope group (group D) and laryngoscope group (group L),40 patients in each group.Group D used Disposcope endoscope for intubation and positio ning while group L used laryngoscope for intubation and auscultation positioning.Patients with difficult intubation,severe ventilation dysfunction and large sputum volume,such as pulmonary hemoptysis and bronchiectasis,were excluded.Intubation and positioning time,airway pressure and arterial carbon dioxide partial pressure (PaCO2) were recorded during double-lung ventilation and OLV,lung collapse effect,and one-time successful intubation ratio,positionging adjustment ratio and the incidence of intubation complications were calculated.Results Intubation and positioning time were significantly longer in group L than in group D [(169.98±52.65)s vs.(102.38±44.45)s](P＜0.05),one-time successful intubation ratio in group L was lower than that in group D (80％ vs.97.5％) (P ＜0.05).The difference of airway pressure and PaCO2 during double-lung ventilation and OLV between the two groups were not statistically significant.The blocker positioning adjust ratio of Univent tube in group L was significantly higher than that in group D (22.5％ vs.7.5％)(P＜0.05).The incidence of bleeding and sore throat after operation in group L were significantly higher than those in group D (27.5％ vs.7.5％,37.5％ vs.15％) (P＜0.05).Conclusion Compare with laryngoscope for intubation and auscultation positioning,Disposcope endoscope used for Univent tube intubation and positioning needs shorter time for intubation and positioning,higher successful one-time intubation ratio,less positioning adjustment.It also reduces the incidence of intubation complications.

Objective To explore the influence of smoking on olfactory disorder in Parkinson's disease (PD). Methods According to smoking or not, 167 PD patients ( PD group) and 100 normal controls ( normal control group) were divided into smoking subgroups and non-smoking subgroups.The olfactory identification threshold was tested by T&T olfactory assessment.Results Compared with normal control group, the scores of MMSE and montreal cognitive assessment in PD group were significantly decreased ( all P<0.05 ) , age, smoking history, the rate of male had no statistical significance ( all P>0.05 ) .The olfactory identification threshold in PD group was significantly higher than normal control group (t=6.785, P=0.000).Compared with PD smoking subgroup, the olfactory identification threshold in non-smoking subgroup was significantly higher (t=-3.000, P=0.003).The olfactory identification threshold in normal control smoking subgroup was significantly lower (t=0.784, P=0.435). The olfactory identification threshold of PD smokers had no correlation with smoking pack-years or duration ( r=-0.104, P=0.441;r=-0.156, P=0.246) .Conclusion Smoking may protect olfactory disorder in PD patients, and it has no correlation with smoking pack-years or duration.