Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.

Objective To observe the value of three-dimensional speckle tracking imaging(3D-STI)in evaluation on right ventricle(RV)function for predicting adverse events in patients with unstable angina(UA)after percutaneous coronary intervention(PCI).Methods A total of 155 UA patients who underwent both 3D-STI and conventional echocardiography and planned to accept PCI were prospectively enrolled and divided into adverse event group(n=37)and control group(n=118)based on the occurrence of adverse events after PCI or not.Clinical data and echocardiographic parameters were compared between groups,and new binary variables were generated according to the optimal cut-off values showed by the maximum Youden index of receiver operating characteristic curves of 3D-STI parameters being statistically different between groups.Then the independent predictors of adverse events among UA patients after PCI were analyzed,a combined model was constructed,and its predictive value was assessed.Results In adverse event group,the left ventricular end diastolic volume(LVEDV)was higher,while the left ventricular ejection fraction(LVEF),right ventricular free wall longitudinal strain(RVFWLS)and right ventricular global longitudinal strain(RVGLS)were all lower than those in control group(all P＜0.05).The optimal cut-off values for distinguishing adverse event or not was 110 ml for LVEDV,19.05%for RVFWLS and 19.75%for RVGLS,respectively,and all the 3 generated binary variables were independent predictors for adverse events of UA patients after PCI(all P＜0.05).The area under the curve of combined model for predicting adverse events in UA patients after PCI was 0.864.Conclusion RVFWLS＜19.05%and RVGLS＜19.75%obtained with 3D-STI,as well as LVEDV＞110 ml with conventional echocardiography were all independent predictors of adverse events in UA patients after PCI.

Objective To observe the value of three-dimensional speckle tracking imaging(3D-STI)in evaluation on right ventricle(RV)function for predicting adverse events in patients with unstable angina(UA)after percutaneous coronary intervention(PCI).Methods A total of 155 UA patients who underwent both 3D-STI and conventional echocardiography and planned to accept PCI were prospectively enrolled and divided into adverse event group(n=37)and control group(n=118)based on the occurrence of adverse events after PCI or not.Clinical data and echocardiographic parameters were compared between groups,and new binary variables were generated according to the optimal cut-off values showed by the maximum Youden index of receiver operating characteristic curves of 3D-STI parameters being statistically different between groups.Then the independent predictors of adverse events among UA patients after PCI were analyzed,a combined model was constructed,and its predictive value was assessed.Results In adverse event group,the left ventricular end diastolic volume(LVEDV)was higher,while the left ventricular ejection fraction(LVEF),right ventricular free wall longitudinal strain(RVFWLS)and right ventricular global longitudinal strain(RVGLS)were all lower than those in control group(all P＜0.05).The optimal cut-off values for distinguishing adverse event or not was 110 ml for LVEDV,19.05%for RVFWLS and 19.75%for RVGLS,respectively,and all the 3 generated binary variables were independent predictors for adverse events of UA patients after PCI(all P＜0.05).The area under the curve of combined model for predicting adverse events in UA patients after PCI was 0.864.Conclusion RVFWLS＜19.05%and RVGLS＜19.75%obtained with 3D-STI,as well as LVEDV＞110 ml with conventional echocardiography were all independent predictors of adverse events in UA patients after PCI.

Objective To determine the effects of dexmedetomidine(Dex)in anesthesia on brain function,cerebral oxygen uptake rate(CERO2),difference in glucose content between cerebral ar-terial and venous blood(A-VDG)and jugular bulb oxygen saturation(SjvO2)and stress response in elderly patients with hypertensive cerebral hemorrhage.Methods A total of 96 elderly patients with hypertensive cerebral hemorrhage admitted to our hospital from January 2021 to June 2024 were recruited,and according to different anesthesia schemes,they were divided into the group A(propofol,remifentanil,sevoflurane combined with rocuronium anesthesia,48 cases)and group B(same anesthesia regimen as group A plus Dex).Glasgow coma(GCS)score and restlessness-sedation score 48 h after operation,postoperative recovery,stress indexes and cerebral glucose and oxygen metabolism before(T1)and at the end of operation(T2),and adverse reactions during the study were compared between the two groups.Results When compared with the group A,the group B had significantly higher GCS score 48 after surgery(13.95±0.28 vs 12.89±0.41,P＜0.01),and shorter awakening time,time to regain spontaneous breathing,extubation time and response time(P＜0.01).At T2,the levels of CERO2,A-VDG and SjvO2 were notably higher,while levels of cortisol,norepinephrine and epinephrine,and activity of renin were remarkably lower in the group B than the group A(P＜0.01).At T2,the both groups obtained increased levels of cortisol,norepinephrine,epinephrine and renin activity and SjvO2,while decreased CERO2 and A-VDG levels than the corresponding levels at T1(P＜0.05).The incidences of nausea and vomiting,cough,chills,restlessness and delirium was obviously lower in the group B than the group A(P＜0.05,P＜0.01).Conclusion For elderly patients with hypertensive cerebral hemorrhage,application of Dex in anesthesia can improve cerebral glucose and oxygen metabo-lism,reduce stress response,maintain the stability of perioperative vital signs,decrease the severi-ty of coma and incidences of delirium,nausea and vomiting,cough,chills,restlessness and other adverse reactions,and thus promote postoperative recovery.

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.

Objective To determine the effects of dexmedetomidine(Dex)in anesthesia on brain function,cerebral oxygen uptake rate(CERO2),difference in glucose content between cerebral ar-terial and venous blood(A-VDG)and jugular bulb oxygen saturation(SjvO2)and stress response in elderly patients with hypertensive cerebral hemorrhage.Methods A total of 96 elderly patients with hypertensive cerebral hemorrhage admitted to our hospital from January 2021 to June 2024 were recruited,and according to different anesthesia schemes,they were divided into the group A(propofol,remifentanil,sevoflurane combined with rocuronium anesthesia,48 cases)and group B(same anesthesia regimen as group A plus Dex).Glasgow coma(GCS)score and restlessness-sedation score 48 h after operation,postoperative recovery,stress indexes and cerebral glucose and oxygen metabolism before(T1)and at the end of operation(T2),and adverse reactions during the study were compared between the two groups.Results When compared with the group A,the group B had significantly higher GCS score 48 after surgery(13.95±0.28 vs 12.89±0.41,P＜0.01),and shorter awakening time,time to regain spontaneous breathing,extubation time and response time(P＜0.01).At T2,the levels of CERO2,A-VDG and SjvO2 were notably higher,while levels of cortisol,norepinephrine and epinephrine,and activity of renin were remarkably lower in the group B than the group A(P＜0.01).At T2,the both groups obtained increased levels of cortisol,norepinephrine,epinephrine and renin activity and SjvO2,while decreased CERO2 and A-VDG levels than the corresponding levels at T1(P＜0.05).The incidences of nausea and vomiting,cough,chills,restlessness and delirium was obviously lower in the group B than the group A(P＜0.05,P＜0.01).Conclusion For elderly patients with hypertensive cerebral hemorrhage,application of Dex in anesthesia can improve cerebral glucose and oxygen metabo-lism,reduce stress response,maintain the stability of perioperative vital signs,decrease the severi-ty of coma and incidences of delirium,nausea and vomiting,cough,chills,restlessness and other adverse reactions,and thus promote postoperative recovery.

AIM: To analyze the clinical characteristics of acute acquired concomitant esotropia(AACE)in patients among different age groups.METHODS: Retrospective analysis of clinical data. A total of 112 non-Swan type AACE patients who underwent surgery at Peking University People's Hospital from January 2015 to December 2022 were retrospectively analyzed. Clinical data were collected and the characteristics were compared, including gender, age, diopter, duration of disease, daily time spent on near work, angles of deviation before and after surgery, stereopsis, etc. According to age, patients were divided into three groups: <18 years old group(22 cases), 18-45 years old group(67 cases), and >45 years old group(23 cases). The clinical characteristics of patients were compared in each group.RESULTS: A total of 112 patients were included in the study, comprising 56 males and 56 females, with a median age of 29.50(19.25, 41.75)years old. Among them, 97 patients had myopia(86.6%). There were 93 patients(83.0%)who spent more than 8 h on near work. The age group <18 years old had the shortest duration before surgery, with a median time of 1.00(0.50, 1.00)a, the minimum negative diopter, with a median diopter of -0.75(-3.19, -0.56)D in the right eye and the diopter of -1.25(-2.81, -0.75)D in the left eye, and the maximum preoperative near angle of deviation, with a median angle of 30.00(18.50, 80.00)PD, and the maximum preoperative distant angle of deviation, with a median angle of 35.00(23.75, 80.00)PD. All these differences were statistically significant compared with other two groups(both P<0.05). For the age group from 18 to 45 years old, the median near angle of deviation was 20.00(14.00, 30.00)PD, and the median distant angle of deviation was 25.00(20.00, 35.00)PD, both of which were higher than those in the age group >45 years old(both P<0.05). For the age group >45 years old, the median near angle of deviation after surgery was -4.50(-7.50, 0)PD, and the median distant angle of deviation after surgery was 4.50(0, 9.50)PD, which were smaller than those in other two groups(all P<0.05). The age group >45 years old had the hiughest surgical success rate(100%). The preoperative stereopsis was better in age group >45 years old than the group <18 years old(P<0.05). The postoperative stereopsis of the age group of 18 to 45 years old and the age group >45 years old was better than age group <18 years old(both P<0.05).CONCLUSION: Surgical patients with AACE are mainly in the age group from 18 to 45 years old. The characteristic of angle of deviation is that distant angle of deviation is greater than near angle of deviation. The patients <18 years old have larger preoperative angles of deviation than adults, while their stereoacuity is worse than adults in the early postoperative period. It is recommended that augmented-dose surgery should be performed in AACE patients who are in the age group of 18 to 45 years old(5-10 PD). A conservative surgery should be designed for hyperopia young children without established binocular vision.

Behavioral activation therapy is a short-term psychological treatment for depression.It has achieved positive results in the treatment of depression due to its simplicity and low treatment cost.Driven by the development of information technology and the aging of population,behavioral activation therapy is constantly innovated to meet the needs of depression treatment.This article reviews the application of behavioral activation therapy in depression treatment,and focuses on the innovative application progress based on the analysis of the connotation and current status of behavioral activation therapy.