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

Objective:To explore the diagnostic value of digital mammography combined with serum glutathione specific gamma-glutamyl transpeptidase 1(CHAC1)and retinoic acid-induced protein 14(RAI14)in identifying benign and malignant breast masses.Methods:A total of 189 patients with breast masses who were treated at Handan Maternal and Child Health Care Hospital from June 2019 to June 2024 were prospectively selected as the research subjects.According to the results of pathological biopsy,they were divided into benign mass group(128 cases)and malignant mass group(61 cases).All patients underwent digital mammography detection.The levels of serum CHAC1 and RAI14 were detected by enzyme-linked immunosorbent assay(ELISA).The general clinical data of the patients were collected and analyzed.Multivariate logistic regression analysis was used to analyze the factors of influencing benign and malignant nature of breast masses.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of CHAC1 and RAI14 for the benign and malignant nature of breast masses.The Kappa test was used to assess the consistency of results between each diagnostic method and the pathological detection.Results:For 189 patients with breast masses,digital mammography identified 56 cases of malignant masses and 133 cases of benign masses,and 13 cases of them were misdiagnosis and 18 cases of them were missed diagnosis.It showed a moderate consistency with the results of pathological detection(Kappa=0.617,P<0.05).Compared with the benign mass group,the levels of serum CHAC1 and RAI14 in the malignant mass group were significantly higher,and the differences of them between the two groups were statistically significant(t=12.249,12.512,P<0.05).The age,menopausal time,CHAC1 and RAI14 of the patients were all risk factors that can affect the benign and malignant nature of breast masses(OR=1.368,1.305,1.897,1.995,P<0.05).The area under curve(AUC),sensitivity and specificity of CHAC1 were respectively 0.816(95%CI:0.753～0.868),70.49%and 89.06%in diagnosing the benign and malignant nature of breast masses.These indicators of RAI14 were respectively 0.838(95%CI:0.778～0.888),68.85%and 89.84%in diagnosing the benign and malignant nature.The combined detection of the three methods identified 74 cases of malignant masses and 115 cases of benign masses,with 15 cases of misdiagnosis and 2 cases of missed diagnosis,which showed an extremely high consistency with the results of pathological detection(Kappa=0.805,P<0.001).The sensitivity(96.72%),negative predictive value(98.26%)and accuracy(91.01%)of the combined detection of digital mammography,serum CHAC1 and RAI14 were significantly higher than those of each alone detection of them,and the differences of them were significant(x2=15.310,16.623,15.310,11.690,12.402,11.572,5.276,5.276,4.677,P<0.05).Conclusion:The levels of serum CHAC1 and RAI14 appear increase in malignant breast masses,and digital mammography combined with serum CHAC1 and RAI14 has a certain of identification value for benign and malignant nature of breast masses.

Objective:To explore the clinical efficacy and safety of endoscopic multi-band ligation (EMBL) in the management of refractory gastroesophageal reflux disease (RGERD) combined with esophageal hiatal hernia (HH).Methods:This study was a prospective, multicenter, small-sample cohort study. Patients who were diagnosed as having RGERD combined with HH at Inner Mongolia Medical University Cancer Hospital and Inner Mongolia Medical University Hospital from January 2020 to June 2022 were selected to undergo EMBL. The 24-hour esophageal pH monitoring and high-resolution manometry (HRM) related indicators, gastroesophageal reflux index (GERI), gastroesophageal reflux disease questionnaire (GERD-Q) scores, and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores were compared before and after the operation. The patient satisfaction and complications were also investigated.Results:A total of 25 patients were included, all of whom were successfully treated with EMBL. Reflux symptoms were relieved to varied degrees in all patients. There were no serious complications during or after the operation, such as perforation, bleeding, and dysphagia. Postoperative follow-up at 6 and 12 months showed a significant decrease in DeMeester scores [18.00 (5.83, 54.75) points, 16.30 (4.38, 60.00) points] compared to preoperative baseline [105.00 (60.80, 147.70) points, Z=-3.72, P<0.001; Z=-3.82, P<0.001]. The percentage of time of pH<4 [8.80 (6.10, 11.80)%, 8.95 (5.15, 10.90)%] significantly decreased compared to the baseline [31.15 (16.75, 54.75)%, Z=-3.72, P<0.001; Z=-3.72, P<0.001], the number of long refluxes [7.90 (4.93, 11.75) times, 6.90 (4.00, 10.75) times] significantly decreased compared to the baseline [33.00 (13.00, 43.00) times, Z=-3.82, P<0.001; Z=-3.58, P<0.001], and the number of acid refluxes (14.86±8.71 times, 12.93±5.51 times) significantly decreased compared to before (30.42±17.99 times, t=5.88, P<0.001; t=4.79, P<0.001). Lower esophageal sphincter resting pressure [9.70 (5.80, 19.58) mmHg, 11.70 (5.40, 19.78) mmHg] was significantly higher compared to before [4.70 (3.25, 7.00) mmHg, Z=-2.84, P<0.001; Z=-3.10, P<0.001]. GERD-Q scores (10.00±2.01 points, 9.43±1.74 points) were significantly higher compared to before (15.34±1.51 points, t=8.90, P<0.001; t=9.87, P<0.001), GERD-HRQL scores [7.00 (5.00, 7.75) points, 6.00 (5.75, 8.25) points] significantly decreased compared to preoperative baseline [13.50 (11.00, 21.25), Z=-3.73, P<0.001; Z=-3.72, P<0.001], and GERI (2.26%±1.58%, 2.07%±1.17%) significantly decreased compared to before (5.72%±2.27%, t=8.92, P<0.001; t=9.86, P<0.001). At 6 and 12 months postoperative follow-up, patient satisfaction [68.00% (15/25), 84.00% (21/25)] significantly increased compared to before [0.00% (0/25), Z=-4.63, P<0.001; Z=-6.48, P<0.001]. Conclusion:Preliminary small-sample study has shown that EMBL is safe, reliable and effective for the treatment of RGERD with HH.

Objective:To explore the diagnostic value of digital mammography combined with serum glutathione specific gamma-glutamyl transpeptidase 1(CHAC1)and retinoic acid-induced protein 14(RAI14)in identifying benign and malignant breast masses.Methods:A total of 189 patients with breast masses who were treated at Handan Maternal and Child Health Care Hospital from June 2019 to June 2024 were prospectively selected as the research subjects.According to the results of pathological biopsy,they were divided into benign mass group(128 cases)and malignant mass group(61 cases).All patients underwent digital mammography detection.The levels of serum CHAC1 and RAI14 were detected by enzyme-linked immunosorbent assay(ELISA).The general clinical data of the patients were collected and analyzed.Multivariate logistic regression analysis was used to analyze the factors of influencing benign and malignant nature of breast masses.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of CHAC1 and RAI14 for the benign and malignant nature of breast masses.The Kappa test was used to assess the consistency of results between each diagnostic method and the pathological detection.Results:For 189 patients with breast masses,digital mammography identified 56 cases of malignant masses and 133 cases of benign masses,and 13 cases of them were misdiagnosis and 18 cases of them were missed diagnosis.It showed a moderate consistency with the results of pathological detection(Kappa=0.617,P<0.05).Compared with the benign mass group,the levels of serum CHAC1 and RAI14 in the malignant mass group were significantly higher,and the differences of them between the two groups were statistically significant(t=12.249,12.512,P<0.05).The age,menopausal time,CHAC1 and RAI14 of the patients were all risk factors that can affect the benign and malignant nature of breast masses(OR=1.368,1.305,1.897,1.995,P<0.05).The area under curve(AUC),sensitivity and specificity of CHAC1 were respectively 0.816(95%CI:0.753～0.868),70.49%and 89.06%in diagnosing the benign and malignant nature of breast masses.These indicators of RAI14 were respectively 0.838(95%CI:0.778～0.888),68.85%and 89.84%in diagnosing the benign and malignant nature.The combined detection of the three methods identified 74 cases of malignant masses and 115 cases of benign masses,with 15 cases of misdiagnosis and 2 cases of missed diagnosis,which showed an extremely high consistency with the results of pathological detection(Kappa=0.805,P<0.001).The sensitivity(96.72%),negative predictive value(98.26%)and accuracy(91.01%)of the combined detection of digital mammography,serum CHAC1 and RAI14 were significantly higher than those of each alone detection of them,and the differences of them were significant(x2=15.310,16.623,15.310,11.690,12.402,11.572,5.276,5.276,4.677,P<0.05).Conclusion:The levels of serum CHAC1 and RAI14 appear increase in malignant breast masses,and digital mammography combined with serum CHAC1 and RAI14 has a certain of identification value for benign and malignant nature of breast masses.

Objective:To explore the clinical efficacy and safety of endoscopic multi-band ligation (EMBL) in the management of refractory gastroesophageal reflux disease (RGERD) combined with esophageal hiatal hernia (HH).Methods:This study was a prospective, multicenter, small-sample cohort study. Patients who were diagnosed as having RGERD combined with HH at Inner Mongolia Medical University Cancer Hospital and Inner Mongolia Medical University Hospital from January 2020 to June 2022 were selected to undergo EMBL. The 24-hour esophageal pH monitoring and high-resolution manometry (HRM) related indicators, gastroesophageal reflux index (GERI), gastroesophageal reflux disease questionnaire (GERD-Q) scores, and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores were compared before and after the operation. The patient satisfaction and complications were also investigated.Results:A total of 25 patients were included, all of whom were successfully treated with EMBL. Reflux symptoms were relieved to varied degrees in all patients. There were no serious complications during or after the operation, such as perforation, bleeding, and dysphagia. Postoperative follow-up at 6 and 12 months showed a significant decrease in DeMeester scores [18.00 (5.83, 54.75) points, 16.30 (4.38, 60.00) points] compared to preoperative baseline [105.00 (60.80, 147.70) points, Z=-3.72, P<0.001; Z=-3.82, P<0.001]. The percentage of time of pH<4 [8.80 (6.10, 11.80)%, 8.95 (5.15, 10.90)%] significantly decreased compared to the baseline [31.15 (16.75, 54.75)%, Z=-3.72, P<0.001; Z=-3.72, P<0.001], the number of long refluxes [7.90 (4.93, 11.75) times, 6.90 (4.00, 10.75) times] significantly decreased compared to the baseline [33.00 (13.00, 43.00) times, Z=-3.82, P<0.001; Z=-3.58, P<0.001], and the number of acid refluxes (14.86±8.71 times, 12.93±5.51 times) significantly decreased compared to before (30.42±17.99 times, t=5.88, P<0.001; t=4.79, P<0.001). Lower esophageal sphincter resting pressure [9.70 (5.80, 19.58) mmHg, 11.70 (5.40, 19.78) mmHg] was significantly higher compared to before [4.70 (3.25, 7.00) mmHg, Z=-2.84, P<0.001; Z=-3.10, P<0.001]. GERD-Q scores (10.00±2.01 points, 9.43±1.74 points) were significantly higher compared to before (15.34±1.51 points, t=8.90, P<0.001; t=9.87, P<0.001), GERD-HRQL scores [7.00 (5.00, 7.75) points, 6.00 (5.75, 8.25) points] significantly decreased compared to preoperative baseline [13.50 (11.00, 21.25), Z=-3.73, P<0.001; Z=-3.72, P<0.001], and GERI (2.26%±1.58%, 2.07%±1.17%) significantly decreased compared to before (5.72%±2.27%, t=8.92, P<0.001; t=9.86, P<0.001). At 6 and 12 months postoperative follow-up, patient satisfaction [68.00% (15/25), 84.00% (21/25)] significantly increased compared to before [0.00% (0/25), Z=-4.63, P<0.001; Z=-6.48, P<0.001]. Conclusion:Preliminary small-sample study has shown that EMBL is safe, reliable and effective for the treatment of RGERD with HH.

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.

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Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Humans ; Atherosclerosis/genetics* ; Autophagy/genetics* ; Cell Cycle Proteins/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; MicroRNAs/metabolism* ; Repressor Proteins/metabolism* ; RNA Splicing Factors ; Serine-Arginine Splicing Factors/genetics* ; RNA, Long Noncoding/metabolism*

Objective: To evaluate the short-term efficacy of branched TEVAR in the treatment of complex aortic arch lesions. Methods: The clinical data of 18 patients with aortic lesions requiring reconstruction of the left subclavian artery who were treated with branch TEVAR technology in Tianjin Medical University General Hospital from Apr 2016 to Dec 2018 were analyzed retrospectively. Results: There were 16 cases using Castor external branch stent implantation and 2 cases of self-made internal branch stent. The success rate of device release was 100%, the success rate of operation was 100%, and there were no intraoperative deaths. Postoperative complications occurred in 2 cases: one proximal stent tear dissection required open surgery, one died of massive myocardial infarction.Seventeen patients were followed up for 1-8 months. CTA examination in 16 patients 30 days after surgery, found 1 patient with type Ⅲ endoleak. CTA examination done in 8 patients 6 months after surgery found distal occlusion of left subclavian artery stent in 1 patient necess itating distal stent implantation. Conclusion The branch TEVAR technique is effective method to reconstruct the arch branched artery.

Objective To observe the effect of electroacupuncture at the beginning and ending points of bicipital muscle on the superficial electromyography (sEMG) of the spastic limb in hemiplegia.Method Forty patients with spastic hemiplegia after cerebral stroke were divided by the random number table into a group of electroacupuncture at the beginning and ending points (group A) and a group of electroacupuncture at antagonistic muscles (group B). The former selected Ashi points at the beginning and ending points of bicipital muscle, while the latter selected points at the antagonistic muscles [Tianjing (TE10), Qinglingyuan (TE11), etc.], to receive perpendicular puncturing. The needles were retained for 30 min, and the sEMG of bicipital muscles in resting state was detected after the removal of the needles. The spastic bicipital muscle was examined by sEMG prior to the acupuncture treatment, and respectively after 2-week and 4-week acupuncture treatment, and the detected parameters included root mean square (RMS) and integrated electromyography (IEMG).ResultThe EMG and IEMG declined gradually in the two groups after the acupuncture treatment; the intra-group comparisons of the RMS and IEMG values at three time points, e.g. prior to acupuncture treatment, after 2-week acupuncture treatment and after 4-weekacupuncture treatment, showed that the values changed significantly compared to those at the previous time point (P<0.05); the between-group comparisons showed that there were no significant differences in comparing the RMS and IEMG values regardless of different time points (P>0.05). The RMS and IEMG values presented same changing tendencies after 4-week acupuncture treatment in the two groups.ConclusionAcupuncture at the beginning and ending points and at the points on antagonistic muscles both can decrease the resting-state muscle tension in hemiplegia patients; sEMG is of certain significance in evaluating the treatment of hemiplegia.