Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Abstract: To date, the investigation of the functional composition of Centella asiatica (L.) Urban has been mainly focused on the triterpenoid saponins, with little research on the other compositions. The acetic acid-induced writhing, Eddy's hot plate and formalin tests were employed to investigate the anti-nociceptive effects of madecassic acid (MA). The experiment was divided into normal control group, acetylsalicylic acid (ASA) group, and the MA groups of low (10 mg/kg), medium (20 mg/kg) and high (40 mg/kg) dosage. Meanwhile, the anti-nociceptive effect of MA on the acetic acid and formalin-induced nociceptive models in the absence and presence of NAL (naloxone hydrochloride) was evaluated. To have an insight into the anti-nociceptive mechanisms of MA, the capsaicin- and glutamate-induced paw licking tests were also employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Results showed that MA exhibited good anti-nociceptive activity in the acetic acid-induced writhing test and the second phase of formalin test; the anti-nociceptive effect of MA in both the acetic acid and formalin-induced nociception was not effectively removed by NAL; MA (20 mg/kg and 40 mg/kg) effectively reduced the duration of biting/licking the capsaicin-injected paw with inhibition rates of 29.5% and 64.4%, respectively; MA (20 mg/kg and 40 mg/kg) distinctly shortened the time spent in biting/licking the glutamate-injected paw by 30.9% and 56.1%, respectively. In summary, MA induces significant peripheral anti-nociceptive effect, and the anti-nociceptive activities probably involve the modulation of glutamatergic systems and vanilloid systems (TRPV1) instead of the opioidergic system.

Objective:To construct an evaluation indicator system for the efficiency of nursing human resources in integrated medical and elderly care institutions using Data Envelopment Analysis (DEA) and subsequently evaluate its effectiveness.Methods:This cross-sectional survey utilized literature review and investigative methods to initially establish a library of evaluation indicators for nursing human resource efficiency. The Delphi method was employed in two rounds of consultations with 17 experts from various fields, including nursing management, elderly care institution management, integrated medical and elderly care institution management, health economics management, and public health. The reliability of the indicator system was assessed based on factors such as expert enthusiasm, authority, concentration of opinions, and coordination. Adjustments, modifications, and improvements were made to the indicators based on expert opinions to establish the final indicator system. From August to December 2022, the DEA model was applied to evaluate the efficiency of 12 integrated medical and elderly care institutions in Haikou city based on this indicator system.Results:The constructed evaluation indicator system comprised 68 items divided into three levels: 9 primary indicators, 19 secondary indicators, and 40 tertiary indicators. The positive coefficients of the two rounds of expert consultations were 100% and 94.1%, with authority coefficients of 0.88 and 0.92, Kendall harmony coefficients of 0.471 and 0.348, and mean coefficients of variation of 0.16 and 0.12 ( P<0.001). DEA evaluation results for the 12 integrated medical and elderly care institutions showed that 5 were DEA effective institutions with comprehensive efficiency (OE), technical efficiency (TE), and scale efficiency (SE) values all equal to 1.000, while 7 were non-DEA effective institutions, including 4 with SE <1.000 but TE=1.000 and 3 with both SE and TE<1.000. Conclusions:The constructed evaluation indicator system demonstrates high enthusiasm, authority coefficients, and coordination in expert consultations, indicating high acceptability and comprehensive content with distinct levels and strong specialty characteristics. The DEA model′s evaluation results objectively and effectively reflect the efficiency of nursing human resources in integrated medical and elderly care institutions, demonstrating practical utility.

This article reported a prenatally diagnosed case of complete ring chromosome 15. A 38-year-old woman who conceived by in vitro fertilization and frozen embryo transfer underwent amniocentesis for prenatal diagnosis at 18 +5 weeks of gestation due to advanced maternal age. The result of G-banding karyotyping was mos 46,XX,r(15)[88]/45,X,-15[11]/46,XX,r(15;15)[1]. No numerical abnormalities of chromosomes or definite pathogenic copy number variations (CNVs) were detected by chromosomal microarray analysis. Amniocentesis was performed again at 31 +6 weeks of gestation. The result of genome copy number variation sequencing indicated no pathogenic CNV and fluorescence in situ hybridization on cultured amniocytes revealed nuc ish(15q)×1[15]/(15q)×3[5]/(15q)×2[80]. Based on all the prenatal diagnosis results, it was suggested that the fetus carried a complete ring chromosome 15. As the peripheral blood chromosomes of the couple were normal and no obvious abnormalities were detected by the prenatal ultrasound either in our hospital or another hospital, the pregnant woman decided to continue the pregnancy after genetic counseling and delivered a baby girl at 41 weeks of gestation. The girl showed no physical abnormalities during a seven-month follow-up.

Objective:To explore any effect of repeated transcranial magnetic stimulation (rTMS) on the upper limb motor function and cerebral cortex activation of stroke survivors.Methods:Sixty stroke survivors were randomly divided into an intervention group and a control group, each of 30. In addition to routine rehabilitation training (including drug therapy, comprehensive hemiplegic limb training and physical factor therapy), the intervention group received 15 minutes of rTMS daily, five days a week for 4 weeks while the control group was given false rTMS. Upper limb motor function was evaluated before and after the treatment using the Fugl Meyer upper limb motor function rating scale (FMA-UE). Functional near-infrared spectroscopy was used to detect and compare the activation (β values) of the prefrontal cortex, the motor cortex and the primary somatosensory cortex in the 2 groups. The correlation between the FMA-UE scores and the β values was quantified.Results:①There was no significant difference in the average FMA-UE scores between the two groups before the treatment. Afterward, though both groups′ average scores had increased significantly, there was significantly greater improvement in the treatment group. ②There was also no significant difference in average β value between the two groups before the experiment, but afterward the average βs of channels 27 and 13 in the intervention group were significantly higher than in the control group. Moreover, in patients with lesion in the left brain, the β-values of CH27 and CH13 were also significantly higher than the control group ( P<0.05). ③The FMA-UE scores of the intervention group were moderately correlated with the CH27 and CH13 β values, but those of the control group were only weakly correlated with the β values of CH27. Conclusion:Transcranial magnetic stimulation activates a lesioned left brain region, improving upper limb motor function. The improvement is correlated with the activation of the left prefrontal cortex and the left primary somatosensory cortex.

Myopia is a significant global health issue,and its exact causes are still not fully understood,leaving a lack of effective and propaqable treatment options.The prevalence of myopia among children and adolescents in China remains high,posing challenges for prevention and control efforts.According to the"theory of imbalance of essence and tendon",an imbalance in the essential elements and tendons can impede the passage of eye essence and blood,resulting in delayed expansion and contraction of the eye meridians and tendons,leading to blurred vision.Modern research indicates that during the development of myopia,there are notable changes in the microstructure,activation range,and signaling of various brain regions,providing a biological basis for the"brain-eye"mechanism.Moreover,abnormal activity in the brain nucleus contributes to alterations in choroid blood flow and the impairment of eye muscle regulation,thereby accelerating the progression of myopia,this phenomenon represents the manifestation of the brain-eye imbalance.Consequently,strategies for myopia prevention and control should prioritize nourishing kidney essence,replenishing brain marrow,promoting liver and blood health,and softening the meridians.These measures aim to optimize the functioning of the brain and eyes,maintain the flexibility of eye tendons,enhance eye regulation,sustain the strength of eye tendons,and delay the advancement of eye axis growth and myopia.By enriching the scientific understanding of the appropriate application of traditional Chinese medicine techniques to prevent and control myopia through the brain,this research provides valuable insights for future explorations in this field.

Objective To systematically evaluate the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.Methods Databases such as PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Data,CBM,and VIP were searched for randomized controlled trials(RCTs)related to the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.The search covered all publications up to June 2023.Statistical analysis was performed using RevMan 5.4 software and Stata 15.0.Results Twelve RCTs were included,involving 2 192 patients,of which 1 154 were in the ciprofol group and 1 038 in the propofol group.Compared with the propofol group,the anesthesia induction time(MD=0.28 min,95％CI 0.08-0.47 min,P=0.006)and recovery time(MD=1.16 min,95％CI 0.44-1.87 min,P=0.001)were significantly longer in the ciprofol group,and the inci-dences of injection pain(OR=0.04,95％CI 0.02-0.06,P＜0.001),hypotension(OR=0.64,95％CI 0.49-0.83,P=0.0008),hypoxemia(OR=0.44,95％CI 0.21-0.91,P=0.03),and respirato-ry depression(OR=0.19,95％CI 0.11-0.32,P＜0.001)were significantly lower.There were no sta-tistically significant differences between the two groups in terms of sedation success rate,physician satisfac-tion,the difference in heart rate before and after anesthesia induction,incidence of body movement,brady-cardia,nausea and vomiting,and dizziness.Conclusion The anesthetic effect of cyclopofol and propofol is similar when used for anesthesia outside the operating room.Compared to propofol,ciprofol offers comparable anesthetic effects for sedation and anesthesia outside the operating room,with a lesser impact on respiratory function and more stable hemodynamics.Ciprofol also significantly lowers the incidence of adverse reactions such as injection pain,hypotension,hypoxemia,and respiratory depression.

Parkinson disease is a common neurodegenerative disease.At present,the main therapeutic drugs have problems such as adverse reactions,lack of targeting,and low bioavailability.The development of new drugs is an important direction for research related to Parkinson disease.TCM flavonoids have various pharmacological activities and are widely used in anti-tumor and cardiovascular disease treatment,but there is relatively little research on their intervention in neurological diseases.This article elaborated on the mechanism of intervention of TCM flavonoids in Parkinson disease and summarized treatment strategies from six categories:flavonoids,flavonols,isoflavones,flavonoid glycosides,dihydroflavonols,and others,with the purpose to provide reference for the research and clinical application of TCM flavonoids.

Objective:To observe the effect of personalized airway clearance therapy on extubation of patients with trache-otomy in intensive rehabilitation care unit. Method:Totally 62 patients who met the inclusion criteria were divided into the control group and experimen-tal group,with 31 patients in each group.During the experimental period,one patient in the control group and experimental group dropped off.The control group was given the posture drainage combined with back tap-ping on the basis of routine rehabilitation,while the experimental group was given the personalized airway clearance therapy(including cough training,active cycles of breathing techriques,posture drainage,etc.)on the basis of routine rehabilitation.The observation period was 6 weeks,and the sputum volume,extubation time,extubation success rate and clinical pulmonary infection score were compared between the two groups. Result:After 6 weeks of training,the average sputum volume in the experimental group was significantly high-er than that in the control group(P＜0.05).At the first week of training,there was no significant difference in the average daily sputum volume between the two groups(P＞0.05),but at the second,fourth and sixth weeks,the average daily sputum volume in the experimental group was significantly lower than that in the control group(P＜0.05).Before training,there was no statistically significant difference in CPIS scores between the two groups(P＞0.05),but at the first,third and sixth weeks,CPIS scores in the experimental group were significantly lower than that in the control group(P＜0.05).The results of repeated measure ANOVA showed that the time effect,inter-group effect and interaction effect of daily expectoration volume and CPIS score in the two groups were statistically significant(P＜0.05).The extubation time in the experimental group was significantly shorter than that in the control group(P＜0.05),and the success rate of extubation in the ex-perimental group was 93.3％,which was significantly higher than 70.0％in the control group(P＜0.05). Conclusion:Personalized airway clearance technology can improve the pulmonary infection of patients with tra-cheotomy in ICU more effectively,shorten the time of tracheal tube removal,and improve the success rate of extubation.

Objective:To observe the effect of personalized respiratory breathing training on pulmonary function in pa-tients with tracheotomy after stroke. Method:Fifty-two post-stroke tracheotomy patients who met the inclusion criteria were divided into a control group(n=26)and an intervention group(n=26).During the observation period,one patient in the control group and one in the intervention group each was lost to follow-up.The control group was given the postural drainage combined with vibration expectoration on the basis of routine rehabilitation,while the intervention group was given individualized breathing training on the basis of the control group.The observation period was 6 weeks,and the pulmonary function,diaphragmatic muscle mobility,diaphragmatic muscle thickening rate,extubation time and extubation success rate were compared between the two groups. Result:Before training,there were no significant differences in pulmonary function indexes(FVC,FEV1 and PEF),diaphragmatic activity(DEq,DEd),and diaphragm thickening rate(DTF)between the two groups(P＞0.05).After 6 weeks of training,the FVC,FEV1,PEF,DEq,DEd and DTF of the two groups were signifi-cantly improved compared with those before training(P＜0.05);and the intervention group was more signifi-cantly improved than the control group(P＜0.05);The extubation time in the intervention group was signifi-cantly shorter than that in the control group(P＜0.05);and the success rate of extubation in the intervention group was 92％,which was significantly higher than that in the control group(68.0％),and the difference was statistically significant(P＜0.05). Conclusion:Personalized respiratory training can more effectively improve the pulmonary function of tracheoto-my patients after stroke,shorten the removal time of tracheal cannula,and improve the success rate of extubation.