Objective To explore the effect of protective ventilation strategies based on individualized positive end expiratory pressure(PEEP)regulated by driving pressure(Pd)in infants under OLV.Methods Sixty infants undergoing elective thoracoscopic surgery were randomly divided into the control group and driving pressure group,with 30 cases in each group.The two groups were compared in terms of MAP,HR,tidal volume(Vt),PEEP,Pd,airway peak pressure(Ppeak),and static lung compliance(Cs),and arterial blood gas during OLV before the artificial pneumothorax(T0),10 min(T1),30 min(T2),and 60 min(T3)after the artificial pneumothorax,and right at the end of the artificial pneumothorax(T4).Results There were no significant differences in MAP,HR,and Vt between the two groups at all the time points(P＞0.05).Both groups showed the increase in Pd and Ppeak and decresase in Cs at T1,T2,and T3(all P＜0.05).PaO2 and OI in both group were decreased and PaCO2 was increased at T2(all P＜0.05).Compared with the control group,the driving pressure group presented lower Pd and Ppeak,higher PEEP and Cs at T1,T2,and T3(P＜0.05),and higher PaO2 and OI(P＜0.05)and no significant differences in PaCO2 and FiO2 at T2(P＜0.05).The rate of rescue ventilation during OLV was lower in the driving pressure group(2 cases)than in the control group(9 cases)(6.9%versus 32.4%,P＜0.05).There was no significant difference in the inci-dence of postoperative complications between the two groups(P＜0.05).Conclusion The individualized positive end expiratory pressure(PEEP)regulated by Pd can optimize the PEEP settings upon infant individuals under OLV and improve the compliance and oxygenation of ventilated lung.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 µg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 µg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.

ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.

Objective:To analyze the clinical characteristics of adult-onset patients with familial neuronal intranuclear inclusion disease (NIID).Methods:The clinical data of 3 patients with familial NIID genetically diagnosed in Department of Neurology, Sixth Affiliated Hospital of Guangzhou Medical University in August 2021, January 2022, and August 2022 were collected. Their clinical manifestations, imaging features, pathological features, Notch2 N-terminal-like C ( NOTCH2NLC) gene mutation characteristics, treatment methods and prognoses were summarized retrospectively. Results:The age of these 3 patients was 73, 67, and 65 years, and the onset age was 68, 64, and 56 years, respectively. The clinical manifestations are highly heterogeneous. In patient 1, the nervous centralis, peripheral nerves and autonomic nerves were involved, appearing dementia, epilepsy, Parkinson's syndrome, muscle weakness and uremia; in patient 2, only the nervous centralis were involved, presenting symptoms of Parkinson's syndrome; in patient 3, peripheral nerves and autonomic nerves were involved, prominently presenting with repeated vomiting. Skull diffusion weighted imaging (DWI) showed asymmetric high signal at the dermo-medullary junction in 3 patients. Acidophilic inclusion bodies in some sudoriferous duct epithelial cells, and vascular endothelial nucleus were found in the skin biopsy of 2 patients. All 3 patients completed NOTCH2NL gene test, and all had GGC repeat amplification mutations with mutation frequency>134. These 3 patients were mainly treated symptomatically, and the disease was still progressed gradually. Conclusion:The clinical manifestations of familial NIID are highly heterogeneous; skull MRI characteristic changes and skin biopsy can help to diagnose NIID and NOTCH2NL gene detection can diagnose NIID.

Objective:To investigate the feasibility and efficacy of distal arc-shaped incision of lunula combined with nail template replantation for the treatment of subungual glomus tumor.Methods:The clinical data with subungual glomus tumor treated in the Department of Orthopedics of First Affiliated Hospital of the University of Science and Technology of China from March 2019 to June 2021 were retrospectively analyzed. Each patient removed the nail, the nail bed was cut into by a distal arc-shaped incision of the lunula. After the tumor was exposed, the tumor was resected completely, the nail bed flap was reduced in situ without suturing. The nail template was made by using the 5 ml syringe barrel or the original nail and poked the drainage holes in it, then the nail template was covered on the nail bed surface, three-point suturing and pressurized fixation, routine dressing change, and the nail template was removed 3 weeks after the procedure. The visual analogue scale (VAS) of pain was recorded preoperative and one month after the operation, and nail bed healing, pain improvement, nail growth, and tumor recurrence were observed. VAS scores before and after surgery were expressed as M( Q1, Q3), and analyzed by Mann-Whitney U test, P<0.05 was considered statistically significant. Results:A total of 37 patients were enrolled, including 5 males and 32 females. The age ranged from 18 to 67 years old, with an average of 39 years old. All patients were confirmed as subungual glomus tumors by postoperative pathology, they were followed up for 6 to 36 months, with an average of 22 months. All of the patients had no obvious pain during the dressing change, after removing the nail template, the nail bed was flat and dry, and no obvious scar formation was found. All postoperative incisions were healed in one stage, the new nail recovered smoothly with a satisfactory appearance, the pain symptoms disappeared completely, and also no recurrence occurred during follow-up. The preoperative VAS score was 5.0 (4.5, 6.0), the VAS score one month after the operation was 0.0 (0.0, 0.0), and the difference was statistically significant ( Z=-7.57, P<0.001). Conclusion:The distal arc-shaped incision of the lunula for the treatment of subungual glomus tumor can effectively protect the germinal matrix of the nail bed, with sufficient tumor exposure, complete resection, and low recurrence rate. At the same time, combined with nail template replantation can significantly reduce nail bed scar formation and effectively prevent postoperative nail deformity. The method is simple, easy to operate, and has significant clinical efficacy.

Objective:To investigate the feasibility and efficacy of distal arc-shaped incision of lunula combined with nail template replantation for the treatment of subungual glomus tumor.Methods:The clinical data with subungual glomus tumor treated in the Department of Orthopedics of First Affiliated Hospital of the University of Science and Technology of China from March 2019 to June 2021 were retrospectively analyzed. Each patient removed the nail, the nail bed was cut into by a distal arc-shaped incision of the lunula. After the tumor was exposed, the tumor was resected completely, the nail bed flap was reduced in situ without suturing. The nail template was made by using the 5 ml syringe barrel or the original nail and poked the drainage holes in it, then the nail template was covered on the nail bed surface, three-point suturing and pressurized fixation, routine dressing change, and the nail template was removed 3 weeks after the procedure. The visual analogue scale (VAS) of pain was recorded preoperative and one month after the operation, and nail bed healing, pain improvement, nail growth, and tumor recurrence were observed. VAS scores before and after surgery were expressed as M( Q1, Q3), and analyzed by Mann-Whitney U test, P<0.05 was considered statistically significant. Results:A total of 37 patients were enrolled, including 5 males and 32 females. The age ranged from 18 to 67 years old, with an average of 39 years old. All patients were confirmed as subungual glomus tumors by postoperative pathology, they were followed up for 6 to 36 months, with an average of 22 months. All of the patients had no obvious pain during the dressing change, after removing the nail template, the nail bed was flat and dry, and no obvious scar formation was found. All postoperative incisions were healed in one stage, the new nail recovered smoothly with a satisfactory appearance, the pain symptoms disappeared completely, and also no recurrence occurred during follow-up. The preoperative VAS score was 5.0 (4.5, 6.0), the VAS score one month after the operation was 0.0 (0.0, 0.0), and the difference was statistically significant ( Z=-7.57, P<0.001). Conclusion:The distal arc-shaped incision of the lunula for the treatment of subungual glomus tumor can effectively protect the germinal matrix of the nail bed, with sufficient tumor exposure, complete resection, and low recurrence rate. At the same time, combined with nail template replantation can significantly reduce nail bed scar formation and effectively prevent postoperative nail deformity. The method is simple, easy to operate, and has significant clinical efficacy.