1.A promising novel local anesthetic for effective anesthesia in oral inflammatory conditions through reducing mitochondria-related apoptosis.
Haofan WANG ; Yihang HAO ; Wenrui GAI ; Shilong HU ; Wencheng LIU ; Bo MA ; Rongjia SHI ; Yongzhen TAN ; Ting KANG ; Ao HAI ; Yi ZHAO ; Yaling TANG ; Ling YE ; Jin LIU ; Xinhua LIANG ; Bowen KE
Acta Pharmaceutica Sinica B 2025;15(11):5854-5866
Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na+/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.
2.Research on clinical application of urine sediment score in the diagnosis of acute kidney injury
Hui ZHANG ; Wei XU ; Linlin QU ; Chunhe ZHAO ; Hongli SHAN ; Qin ZHANG ; Hongchen GAO ; Wenrui SUN ; Lina ZHU ; Yue ZHANG ; Xin YAN ; Xiaoquan YANG ; Wanning WANG ; Dong ZHANG ; Yao FU ; Xu ZHAO ; Liang HE
Chinese Journal of Laboratory Medicine 2024;47(5):548-553
Objective:To evaluate the clinical application of urine sediment score (USS) in early diagnosis, etiological differentiation, staging and prognosis of acute kidney injury (AKI), and to investigate the diagnostic efficacy of independent USS and its combination with blood urea nitrogen(Bun) serum creatinine(sCr) and uric acid(UA) in AKI.Methods:From August 23 to September 28, 2023, 9 020 morning urine samples of hospitalized patients in the First Hospital of Jilin University were detected by Sysmex UF5000.A total of 3 226 ssamples with small and round cell (SRC) > 1/μl and/or CAST>1/μl were screened for microscopic examination, and 404 cases with positive renal tubular epithelial cells and/or cast were enrolled in this study. There were 218 males and 186 females, aged 59.5 (49.0, 71.0) years. The 404 cases were divided into the USS AKI group (345 cases) and the USS non-AKI group (59 cases) according to the USS results based on the microscopic findings. According to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, they were divided into KDIGO criteria AKI group (63 cases) and KDIGO criteria non-AKI group (341 cases), and the AKI group was divided into renal AKI group (33 cases) and non-renal AKI group (30 cases). According to the clinical diagnosis recorded in the medical records, they were divided into clinically diagnosed AKI group (29 cases) and clinically diagnosed non-AKI group (375 cases).The χ 2 test or Fisher exact test was used to compare USS in different AKI causes and stages. Logistic regression was used to calculate the odds ratio of renal AKI and stage 3 AKI. The area under the receiver operating characteristic curve was used to evaluate the sensitivity and specificity of USS, sCr, UA and Bun alone and in combination in the diagnosis of AKI, and the best cut-off value, sensitivity and specificity in the diagnosis of AKI were calculated. P < 0.05 was considered statistically significant. Results:The USS was used to identify the etiology of KDIGO standard AKI group,and there were significant differences in USS between renal AKI group and non-renal AKI group (χ 2=11.070, P<0.001). Compared to USS=1, the odds ratio of renal AKI was 8.125 when USS≥2 (95% CI 2.208—29.901). There was a statistically significant difference in the comparison of USS between groups in each stage of the AKI staging study based on USS (χ 2=15.724, P<0.05). Compared to USS=1, the odds ratio of stage 3 AKI was 9.714 when USS≥2 (95% CI 1.145-82.390). The AUC of independent USS in the diagnosis of AKI was 0.687 (95% CI 0.618-0.757, P<0.001), the specificity was 65.7% and the sensitivity was 61.9%. The AUC of USS combined with Bun, sCr, UA in the diagnosis of AKI was 0.794 (95% CI 0.608-0.980, P<0.05), the specificity was 82.4%, and the sensitivity was 88.9%. Conclusions:There wasan increased likelihood of renal AKI or stage 3 AKI while USS≥2,and whose combination with Bun, sCr and UA will improve the diagnostic efficiency of AKI.
3.Efficacy of different modes of high-flow nasal cannula oxygen in preventing hypoxemia during general anesthesia in obese patients without intubation
Liang WANG ; Xiaoyu LIU ; Wenrui SHEN ; Ning YIN
Chinese Journal of Anesthesiology 2023;43(12):1490-1494
Objective:To assess the efficacy of different modes of high-flow nasal cannula (HFNC) oxygen therapy modes in preventing hypoxaemia during general anesthesia in obese patients without endotracheal intubation.Methods:Eighty-four American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-64 yr, with body mass index ≥ 30 kg/m 2, undergoing non-intubated general anesthesia surgery, were divided into 3 groups ( n=28 each) by a random number table method: nasal cannula oxygen therapy group (NC group), HFNC oxygen therapy full-course non-pure oxygen group (HFNC1 group) and HFNC oxygen therapy half-course non-pure oxygen group (NHFC2 group). NC group received oxygen through bilateral nasal cannula, and the oxygen flow rate was 5 L/min, and the oxygen flow rate remained unchanged after anesthesia induction. In NHFC1 group, the flow rate was 30 L/min and the FiO 2 was 41%, and the flow rate was adjusted to 60 L/min after anesthesia induction, and the FiO 2 remained unchanged. NHFC2 group received HFNC oxygen inhalation with a flow rate of 30 L/min and FiO 2 100%, and the flow rate was adjusted to 60 L/min and FiO 2 41% after anesthesia induction. Sufentanil 0.1 μg/kg was intravenously injected after 3 min of oxygen pre-inhalation and target effect-site concentration of propofol was 4 μg/ml in open-loop TCI mode, the closed-loop mode was used to continue intravenous infusion of propofol when the BIS value reached 60 with the same target effect-site concentration, and the intraoperative BIS value was maintained at 45-60. The occurrence and total duration of hypoxemia (SpO 2 <92%) and the lowest value of SpO 2 during anesthesia were recorded. Arterial blood gas analysis was performed before anesthesia induction, at 3 min of oxygen pre-inhalation and at 10 min after anesthesia, and PaO 2 and PaCO 2 were recorded. Respiratory interventions and adverse events were recorded. Results:One patient was excluded due to change of anesthesion method in NC group.Compared with NC group, the incidence of hypoxemia was significantly decreased, the total duration of hypoxemia was shortened, the lowest value of SpO 2 was increased, and the usage rate of respiratory intervention methods was decreased, and PaO 2 was increased and PaCO 2 was decreased at 3 min of oxygen pre-inhalation and 10 min after anesthesia in HFNC2 group ( P<0.05), and PaCO 2 was significantly decreased at 3 min of oxygen pre-inhalation, PaO 2 was increased and PaCO 2 was decreased at 10 min after anesthesia ( P<0.05), and no significant change was found in the other parameters in HFNC1 group ( P>0.05). Compared with HFNC1 group, the incidence of hypoxemia was significantly decreased, the total duration of hypoxemia was shortened, the lowest value of SpO 2 was increased, the usage rate of respiratory intervention methods was decreased, and PaO 2 was increased at 3 min of oxygen pre-inhalation in HFNC2 group ( P<0.05). There was no significant difference in adverse events between the three groups ( P>0.05). Conclusions:HFNC in the mode of FiO 2 100% during oxygen pre-inhalation and FiO 2 41% during anesthesia maintenance can reduce the occurrence of hypoxemia during general anesthesia in obese patients without intubation.
4.Clinical characteristics of aplastic anemia patients with abnormal autoantibodies and the impact of autoantibodies on immunosuppressive therapy response
Weiru LIANG ; Rui KANG ; Xin ZHAO ; Li ZHANG ; Liping JING ; Wenrui YANG ; Yuan LI ; Lei YE ; Kang ZHOU ; Jianping LI ; Huihui FAN ; Yang YANG ; Youzhen XIONG ; Fengkui ZHANG
Chinese Journal of Internal Medicine 2023;62(10):1200-1208
Objective:To investigate the clinical characteristics of patients with acquired aplastic anemia (AA) accompanied by abnormal antinuclear antibody (ANA) and autoantibodies and their effects on the efficacy of immunosuppressive therapy (IST).Method:A retrospective case-control study was conducted, analyzing the clinical data of 291 patients with AA who underwent IST and were screened for autoantibodies at initial diagnosis between January 2018 and December 2019 at Blood Diseases Hospital, Chinese Academy of Medical Sciences. According to the titer of ANA at the initial diagnosis, extracted nuclear antigen antibodies (ENAs) abnormality and the change of ANA titer after treatment, the treatment responses of 3 months and 6 months after IST were compared. The correlation between clinical features and ANA abnormality was analyzed by univariate and multivariate logistic regression analysis. The parameters of univariate analysis P<0.1 were included in multivariate analysis, stepwise regression analysis and subgroup analysis. Results:A total of 291 patients were included in the study, of which 145 (49.83%) were male. Among all patients, 147 (50.52%) tested positive for ANA at initial diagnosis, with titers of 1∶100, 1∶320, and 1∶1 000 observed in 94, 47, and 6 cases, respectively. Female gender, older age, presence of paroxysmal nocturnal hemoglobinuria (PNH) clone, and higher levels of IgG, IgA, and thyroid hormone were significantly associated with ANA positivity at initial diagnosis, while white cell counts, reticulocytes, and free triiodothyronine were significantly lower than that of ANA-negatively patients (all P<0.05). Furthermore, logistic regression analyses revealed that female gender ( OR=1.980, 95% CI 1.206-3.277), older age ( OR=1.017, 95% CI 1.003-1.032), and presence of PNH clone ( OR=1.875, 95% CI 1.049-3.408) were independent risk factors for ANA positivity at initial diagnosis. Subgroup analysis indicated that the risk of ANA positivity at initial diagnosis was even higher in PNH clone-positive patients in the subgroups of females ( OR=1.24, 95% CI 1.02-1.51), severe AA ( OR=1.26, 95% CI 1.07-1.47), and age≥40 years ( OR=1.26, 95% CI 1.05-1.52) (all P<0.05). However, ANA titers at initial diagnosis, presence of other abnormal ENAs, and changes in ANA titers after treatment with IST were not correlated with treatment response (all P>0.05). Conclusions:Approximately 50% of patients with AA had abnormal ANA, and their presence was significantly associated with female gender, older age, and presence of PNH clone at initial diagnosis. However, the presence of abnormal ANA and changes in ANA titers after treatment did not affect the efficacy of IST in patients with AA.
5.Application of apparent diffusion coefficient in glioma classification and glioma microstructure evaluation
Xiangying LI ; Wenrui SU ; Danfeng WANG ; Chenggong YAN ; Qizhou LIANG ; Liu NIE ; Shiwang WANG ; Guang YANG ; Yuan YUAN
Journal of Chinese Physician 2022;24(8):1160-1164
Objective:To explore the application value of apparent diffusion coefficient (ADC) of magnetic resonance diffusion weighted imaging (DWI) parameters in glioma classification and glioma microstructure evaluation.Methods:From June 2017 to November 2019, 38 patients with glioma confirmed by surgery and pathology in Haikou Hospital Affiliated to Xiangya Medical College of Central South University were retrospectively analyzed. According to the pathological results, they were divided into low-grade (WHO Ⅰ-Ⅱ, 15 cases) glioma group and high-grade (WHO Ⅲ-Ⅳ, 23 cases) glioma group. They received magnetic resonance imaging (MRI) plain scan and DWI scan respectively, and the ADC value and microstructure of different grades of glioma were compared. The correlation between ADC value of glioma and the percentage of vascular endothelial growth factor (VEGF)-positive cells, cell density and integrated optical density (IOD) value of aquaporin 1 (AQP1) expression was analyzed.Results:(1) MRI examination showed that the signals of low-grade glioma were more uniform, with no or slight peritumoral edema and space occupying effect, and the enhancement was more non enhanced or slightly enhanced. The signals of high-grade glioma were more heterogeneous due to necrosis and bleeding, and the peritumoral edema and space occupying effect were more obvious, showing uneven obvious enhancement or irregular ring enhancement; (2) The percentage of VEGF positive cells, cell density and the IOD value of AQP1 expression in high-grade glioma were significantly higher than that in low-grade glioma, and the ADC value was lower than that in low-grade glioma (all P<0.05); (3) The ADC value of glioma patients was negatively correlated with the percentage of VEGF-positive cells, cell density, and the IOD value of AQP1 expression ( r=-0.55, -0.65, -0.63, all P<0.05). Conclusions:The ADC value of glioma can indirectly reflect the expression of VEGF, cell density and AQP1 positive expression level, which is helpful for preoperative glioma classification and evaluation of glioma microstructure and biological characteristics.
6.Effect of low-to-moderate dose glucocorticoids on viral clearance in COVID-19: a retrospective study
Qin NI ; Cheng DING ; Yongtao LI ; Hong ZHAO ; Jun LIU ; Xuan ZHANG ; Yanfei CHEN ; Yongzheng GUO ; Liang YU ; Hongzhen JU ; Jingjing TAO ; Ping YI ; Guanjing LANG ; Junwei SU ; Ding SHI ; Wenrui WU ; Xiaoxin WU ; Ling YU ; Jifang SHENG ; Kaijin XU
Chinese Journal of Clinical Infectious Diseases 2020;13(1):21-24
Objective:To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19.Methods:A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg -1·d -1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results:The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years ( χ2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups ( P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days ( P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups ( P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group ( P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively ( P>0.05). Conclusions:Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.
7. Retrospective study of low-to-moderate dose glucocorticoids on viral clearance in patients with novel coronavirus pneumonia
Qin NI ; Cheng DING ; Yongtao LI ; Hong ZHAO ; Jun LIU ; Xuan ZHANG ; Yanfei CHEN ; Yongzheng GUO ; Liang YU ; Hongzhen JU ; Jingjing TAO ; Ping YI ; Guanjing LANG ; Junwei SU ; Ding SHI ; Wenrui WU ; Xiaoxin WU ; Ling YU ; Jifang SHENG ; Kaijin XU
Chinese Journal of Clinical Infectious Diseases 2020;13(0):E009-E009
Objective:
To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19.
Methods:
A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg-1·d-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups.
Results:
The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (
8.Periodic revalidation of autoverification for blood analysis and its suitability evaluation of application
Yingtong LI ; Xuejun WANG ; Wei XU ; Linlin QU ; Xianqiu CHEN ; Lijing WEI ; Ying WANG ; Hongli SHAN ; Zongxing YANG ; Yue CAI ; Xiaoquan YANG ; Wenrui SUN ; Dan LI ; Yue ZHANG ; Xi WANG ; Jin LIANG ; Jing HUANG ; Jiancheng XU ; Haiyan WANG ; Fang LIU ; Weining JIANG ; Chengming SHANG
Chinese Journal of Laboratory Medicine 2020;43(10):1021-1031
Objective:To conduct periodic revalidation of the 15 items and 43 terms autoverification rules of blood analysis after 1 year of application, analyze the application suitability and make the rules improved.Methods:Track the results of 528 010 blood analysis samples of our hospital from August 1, 2019 to January 31, 2020, and analyze the pass rate and interception rate of autoverification; 600 specimens in total were selected randomly for microscope examination, including 300 specimens which touched autoverification rules (1 012 items of autoverification rules) and were intercepted by autoverification and 300 specimens which untouched autoverification rules and were released by autoverification. The abnormal characteristics and unacceptable Delta check of the specimens also need to be concerned at the same time.The false negative rate and false positive rate, true negative rate, true positive rate and pass correct rate of autoverification were verified and compared with the rate of the second phase verification when the autoverification rule was established. The false negative rate, false positive rate, true negative rate and true positive rate of the Delta check rule which 54 716 specimens touched were calculated and compared with the second phase verification rate when the autoverification rule was established.The results of microscopic examination were used as the gold standard for the calculation of the rates, and P<0.05 was considered as a significant difference. The false positive and true positive of 1 012 autoverification rules were analyzed item by item.The false positive and true positive of 108 specimens which touched blast cell autoverification rule were analyzed terms by terms. The mean TAT and median TAT of 528 010 specimens and 193 750 outpatient specimens were calculated respectively, and the report percentages of 528 010 samples that TAT<30, 30-60 and>60 min were calculated respectively. Analyze and evaluate the application suitability of autoverification rules to juge whether they meet the needs of doctors and laboratory. The design process and the rules and application process of autoverification were optimized and improved.Results:The autoverification pass rate was 63.06% (332 971/528 010), the interception rate was 36.94% (195 039/528 010). The false negative rate was 1.00% (1/600), the false positive rate was 12.67% (76/600), the true negative rate was 49% (294/600), the true positive rate was 37.33% (224/600), and the correct rate was 98% (294/300). The pass rate, true negative rate, true positive rate and correct rate of the periodic reverification group were higher than the second phase verification group, the false negative rate and false positive rate were lower than that the second phase verification group. The false negative rate and true positive rate of the Delta check of periodic verification group were lower than that the second phase verification group, the false positive rate and true negative rate were higher than the second phase verification group, there were significant differences in the comparition results. The mean TAT of 528 010 specimens was25 min, and the median TAT was 22 min. The mean TAT of 193 750 outpatient specimens was 23 min, and the median TAT was 20 min. The report percentages of 528 010 samples that TAT<30 min, 30 min-60 min and>60 min were 83.30% (439 819/528 010), 8.00% (42 250/528 010) and 8.70% (45 941/528 010), respectively.Conclusion:The results of periodic revalidation of autoverification after 1 years application show that the 15 items and 43 terms autoverification rules of blood analysis could meet requirements about the accuracy and efficiency of the laboratory, and have a good suitability for application.
9.Continuing nursing mode based on theory of use and satisfaction in patients with PICC
Shiyao LIANG ; Xiufen ZHAO ; Aiwei HUANG ; Wenrui SUN ; Haixia CHEN ; Bin ZHANG
Chinese Journal of Modern Nursing 2020;26(11):1495-1499
Objective:To explore the effects of continuing nursing mode based on theory of use and satisfaction in patients with peripherally inserted central catheter (PICC) .Methods:From August 2017 to June 2018, this study selected 400 patients with PICC as subjects in the First Affiliated Hospital of Wenzhou Medical University.All of patients were divided into control group and intervention group with the method of random number table, 200 cases in each group. Control group carried out the routine nursing. Intervention group analyzed the needs of patients for content and form of continuing nursing, and built the PICC continuing nursing intervention plan based on the theory of use and satisfaction. This study compared the incidence of catheter-related and unplanned extubation, self-management ability, nursing satisfaction of patients between two groups after intervention.Results:After intervention, the incidences of catheter-related complications and unplanned extubation of intervention group were 1.5% and 0 respectively lower than those (16.0% and 5.0%) of control group with statistical differences ( P<0.05) . In intervention group, the scores of the daily catheter observation, maintenance compliance, catheter management confidence, exception handling of catheter, information acquisition, motion with catheter, daily life with catheter and total score of self-management ability, and nursing satisfaction of patients were higher than those in control group with statistical differences ( P<0.05) . Conclusions:Continuing nursing mode based on theory of use and satisfaction can reduce the incidence of catheter-related and unplanned extubation in patients with PICC, improve patients' catheter self-management ability as well as nursing satisfaction which is worthy of being widely used in clinical application.
10. Effects of rope band therapy training on lower extremity motion function in children with spastic cerebral palsy
Xin LI ; Xiaoping WU ; Limei YU ; Wenrui LIANG
Chinese Journal of Applied Clinical Pediatrics 2019;34(24):1871-1875
Objective:
To investigate the application of rope band therapy training on lower extremity motion function of children with spastic cerebral palsy.
Methods:
A total of 55 children with spastic cerebral palsy were admitted to the Second Hospital Affiliated to Guangxi Medical University from January 2017 to March 2018, 27 males and 28 females, and the average age was(51.2±1.7)months.They were divided into a regular group (28 cases) and a rope band therapy training group (27 cases) according to random number table.The regular group included 14 males and 14 females, aged 2 to 6 years old, the mean age was (51.3±1.8) months; the rope therapy training group included 13 males and 14 females, aged 2 to 6 years old, the mean age was (51.1±1.9) months.The regular group was only treated by routine rehabilitation training.On the basis of routine rehabilitation training, the rope therapy training group also underwent the rope therapy training.Before and after 12 weeks of treatment, the 2 groups of children were evaluated and compared by Ashworth improved rating scale (MAS), children balance scale (PBS) and gross motor function test scale(GMFM-88 D and E regions).
Results:
After 12 weeks of treatment, the MAS score of the regular group was (2.64±1.63) scores, the PBS score was (25.44±9.71) scores, the GMFM score of D regions score was (23.82±3.61) scores and E regions score was (26.34±8.81) scores. The MAS score of the rope therapy training group was (2.11±8.75) scores, the PBS (31.92±6.84) scores, the GMFM score of D region was (27.75±6.81) scores, and E region (31.92±6.84) scores.All evaluation criteria of 2 groups of children were improved than those before treatment (all

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