1.Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock(2025)
Wei HUANG ; Xinchen WANG ; Wenzhao CHAI ; Keliang CUI ; Bo YAO ; Zhiqun XING ; Cui WANG ; Jingjing LIU ; Shiyi GONG ; Dongkai LI ; Wanhong YIN ; Xiaoting WANG ; Wei DU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):40-58
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the
2.Effect of Modified Zhigancao Granules (炙甘草汤加味颗粒) on Early Recurrence Following Radiofrequency Ablation in Patients with Atrial Fibrillation of Qi-Yin Deficiency Syndrome:A Randomized,Double-Blind,Placebo-Controlled Trial
Yucai HU ; Boyong QIU ; Jingjing WEI ; Bin LI ; Zuoying XING ; Huixia PENG ; Mingjun ZHU ; Yongxia WANG
Journal of Traditional Chinese Medicine 2025;66(23):2460-2466
ObjectiveTo evaluate the clinical effectiveness and safety of Modified Zhigancao Granules (炙甘草汤加味颗粒) for preventing the early recurrence following radiofrequency ablation in patients with atrial fibrillation (AF) of qi-yin deficiency syndrome. MethodsA multi-center, randomized, double-blind, placebo-controlled trial was designed. A total of 116 patients with atrial fibrillation of qi-yin deficiency syndrome who underwent radiofrequency ablation for the first time were enrolled from 3 centers, and they were randomly divided into a treatment group (59 cases) and a control group (57 cases). Both groups received basic western medicine treatment after surgery. In addition, the treatment group was given oral Modified Zhigancao Granules, while the control group was given oral placebo granules. The dosage for both groups was 20 g each time, twice a day, with continuous treatment for 12 weeks. The recurrence of atrial fibrillation in both groups was recorded at 24 hours, 4 weeks, 8 weeks, and 12 weeks after surgery. The serum levels of B-type natriuretic peptide (BNP), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) were detected before treatment and 12 weeks after treatment in both groups. The scores of Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) Questionnaire (including scores of the daily life dimension, symptom dimension, treatment worry dimension, treatment satisfaction dimension, and total score) and traditional Chinese medicine (TCM) syndrome scores were compared before treatment and at 4 weeks, 8 weeks, and 12 weeks between groups. Safety indicators such as blood routine, urine routine, liver function, and renal function were monitored before and after treatment. ResultsNine of the treatment group and seven of the control group dropped out. Finally, 50 patients in each group were included in the statistical analysis. At 24 hours, 4 weeks, 8 weeks, and 12 weeks after surgery, the recurrence rates of AF in the treatment group were 2.0% (1/50), 2.0% (1/50), 4.0% (2/50), and 10.0% (5/50), respectively; while those in the control group were 2.0% (1/50), 26.0% (13/50), 28.0% (14/50), and 34.0% (17/50), respectively. Compared with the control group at the same time points, the early recurrence rates of AF in the treatment group were significantly lower at 4 weeks, 8 weeks, and 12 weeks after surgery (P<0.01). Compared with the baseline within group, BNP, hs-CRP, IL-6, and TNF-α in the treatment group all decreased after 12 weeks of treatment (P<0.05); the difference in hs-CRP levels (before vs. after treatment) in the treatment group was higher than that in the control group (P<0.01). Compared with the baseline within group, both groups showed decreases in the total score of AFEQT Questionnaire, scores of the daily life dimension, treatment worry dimension, symptom dimension, and TCM syndrome scores at 4 weeks, 8 weeks, and 12 weeks after treatment. Meanwhile, the score of the treatment satisfaction dimension of AFEQT increased in both groups (P<0.01), and the improvements in all the above scores in the treatment group were superior to those in the control group at all time points (P<0.05 or P<0.01). All safety indicators of patients in both groups were within the normal range before treatment and at 12 weeks after treatment, and no adverse reactions or adverse events occurred in either group. ConclusionModified Zhigancao Granules can reduce the early recurrence rate following radiofrequency ablation in AF patients with qi-yin deficiency syndrome, improve clinical symptoms and quality of life, suppress inflammatory response, and show good safety.
3.Role of hippocampal activating transcription factor 5 in cognitive impairment induced by neuropathic pain in mice: relationship with mitochondrial unfolded protein response
Fei XING ; Xiaoshan SHI ; Yaowei XU ; Xin WEI ; Mingcui QU ; Dan CHENG ; Jingjing YUAN ; Zhongyu WANG ; Na XING ; Yanna LI
Chinese Journal of Anesthesiology 2025;45(3):329-334
Objective:To evaluate the role of hippocampal activating transcription factor 5 (ATF5) in cognitive impairment induced by neuropathic pain and the relationship with mitochondrial unfolded protein response(mtUPR) in mice.Methods:This study was conducted in 2 parts. Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups ( n=12 each) using a random number table method: sham operation group (S1 group) and neuropathic pain group (NP group). Neuropathic pain was induced by chronic constriction injury to the sciatic nerve. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model and at 7, 14, 21 and 28 days after developing the model. Mouse cognitive function was assessed using the novel object recognition test from 30-31 days after developing the model. After the end of the novel object recognition test, mice were sacrificed and the hippocampal CA1 region was harvested for determination of the expression of ATF5 (by Western blot) and the expression of ATF5 in neurons, microglia and astrocytes (by immunofluorescence double staining). Experiment Ⅱ Thirty-six SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S2 group), neuropathic pain + ATF5 up-regulation group (NA group), and neuropathic pain + empty virus group (NE group). On day 14 after developing the model, a virus that specifically up-regulated ATF5 expression in neurons and empty virus were injected into the hippocampal CA1 region. The MWT and TWL were measured at days 28 and 35 after developing the model. The novel object recognition test was performed on day 36 after developing the model to evaluate the cognitive function. After the end of the behavioral test, mice were sacrificed and the hippocampal CA1 region was harvested for detection of the expression of ATF5 and mtUPR marker proteins (Lon protease [LONP1] and heat shock protein 60 [HSP60]) by Western blot. Results:Experiment Ⅰ Compared with S1 group, no statistically significant change was found in the MWT and TWL before developing the model ( P>0.05), the MWT and TWL were significantly decreased on days 7, 14, 21 and 28 after developing the model, the discrimination index (DI) was decreased at day 31 after developing the model, the expression of ATF5 was down-regulated, the expression of ATF5 in neurons was down-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF5 in mircrolia and astrocytes in NP group ( P>0.05). Experiment Ⅱ Compared with S2 group, the MWT and TWL were significantly decreased on days 28 and 35 after developing the model in NE group and NA group, DI was decreased, and the expression of ATF5, LONP1 and HSP60 was down-regulated in NE group ( P<0.05), and no significant change was found in NA group ( P>0.05). Compared with NE group, no significant change was found in the MWT and TWL in NA group ( P>0.05), DI was significantly increased, and the expression of ATF5, LONP1 and HSP60 was up-regulated in NA group ( P<0.05). Conclusions:Down-regulated ATF5 in the hippocampus is involved in the process of cognitive impairment caused by neuropathic pain, and the mechanism may be related to the inhibition of mtUPR.
4.Effects of vitamin D deficiency on IVF-ET pregnancy outcomes in women with PCOS and normal ovarian reserve
Jingjing XING ; Yan YUE ; Rong LI ; Fuqing ZHANG ; Min LIU ; Xinxiang MA
Chinese Journal of Reproduction and Contraception 2025;45(2):142-153
Objective:To investigate the impact of vitamin D deficiency on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with polycystic ovary syndrome (PCOS) and normal ovarian reserve (NOR). Methods:A retrospective cohort study was conducted on infertile women undergoing their first IVF-ET cycle in the Department of Reproductive Genetics, Zhengzhou Maternity and Child Health Care Hospital from January 2018 to December 2023, including 318 PCOS patients (group P) and 528 NOR patients (group N). Each group was divided into three subgroups according to serum 25-hydroxyvitamin D [25(OH)D] levels: severe deficiency [25(OH)D<12 μg/L], deficiency [12 μg/L≤25(OH)D<20 μg/L], and non-deficiency [25(OH)D≥20 μg/L]. The impact of vitamin D deficiency on pregnancy outcomes was analyzed in each group. 1∶1 propensity score matching was applied to match the baseline characteristics between group P and group N , resulting in 158 matched cases of PCOS (group P) and NOR (group N). Pregnancy outcomes were compared between the two groups under the same vitamin D status.Results:1) Among PCOS patients, there were no significant differences in general characteristics and pregnancy outcomes among the three subgroups (all P>0.05). The two pronuclei (2PN) rate in the severe deficiency subgroup [59.93% (721/1 203)] was significantly lower than that in the deficiency subgroup [63.70% (1 032/1 620)], with a statistically significant difference ( P=0.045), and both were lower than that in the non-deficiency subgroup [68.06% (554/814)], with a statistically significant difference ( P<0.001, P=0.037). There were no statistically significant differences in the number of oocytes retrieved and MⅡ oocytes, MⅡ oocyte rate, 2PN number, 2PN rate, cleavage number, cleavage rate, number of available embryos on day 3 (day 3, D3), number of high-quality embryos on D3, D3 high-quality embryo rate, clinical pregnancy rate, embryo implantation rate, early miscarriage rate, live birth rate, and premature birth rate among subgroups (all P>0.05). Female age ( OR=0.930, 95% CI: 0.871-0.992, P=0.028), endometrial thickness on the day of transfer ( OR=0.877, 95% CI: 0.791-0.971, P=0.012), number of D3 high-quality embryos ( OR=1.135, 95% CI: 1.050-1.228, P=0.001), and ovulation stimulating protocol ( OR=2.230, 95% CI: 1.153-4.314, P=0.017) were independent factors influencing clinical pregnancy. 2) Among NOR patients, there were no significant differences in general characteristics, pregnancy outcomes, laboratory parameters, or other outcome-related indices among the three subgroups (all P>0.05). Female age ( OR=0.944, 95% CI: 0.900-0.990, P=0.018), number of D3 high-quality embryos ( OR=1.070, 95% CI: 1.004-2.597, P=0.037), and number of transferred embryos ( OR=1.753, 95% CI: 1.184-2.597, P=0.005) were independent factors influencing clinical pregnancy. 3) After matching, there were no significant differences in baseline characteristics and pregnancy outcomes between group P and group N (all P>0.05). In the severe vitamin D deficiency state, group P had significantly lower MⅡ oocyte rate [76.64% (525/685)], 2PN rate [59.69% (345/578)], embryo implantation rate [35.71% (30/84)], and live birth rate [34.00% (17/50)] compared with group N [81.58% (465/570), P=0.033; 67.00% (335/500), P=0.013; 51.28% (40/78), P=0.046; 55.32% (26/47), P=0.035]. In the vitamin D deficiency state, the 2PN rate in group P [66.50% (532/800)] was significantly lower than that in group N [72.00% (725/1 007), P=0.012]. Conclusion:Vitamin D deficiency may adversely affect IVF-ET outcomes in patients with PCOS, with more pronounced effects in cases of severe deficiency. However, it has no impact on the assisted reproductive outcomes in NOR patients.
5.Impact of fresh and frozen-thawed embryo transfer on pregnancy outcomes in elderly women with DOR
Jingjing XING ; Zheng WANG ; Rong LI ; Li LI
Chinese Journal of Reproduction and Contraception 2025;45(6):591-599
Objective:To investigate the impact of fresh and frozen-thawed embryo transfer on pregnancy outcomes in patients with diminished ovarian reserve (DOR) at an advanced age.Methods:Using a retrospective cohort study design, we enrolled elderly women with DOR who underwent their first in vitro fertilization and embryo transfer (IVF-ET) treatment at Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital between January 2018 and December 2022. Patients were grouped according to the cycle type of their first embryo transfer: a fresh cycle transfer group (group A, n=563) and a frozen-thawed cycle transfer group (group B, n=234). Propensity score matching (PSM, 1∶1) was used to match the baseline characteristics and embryo transfer information of the two groups, resulting in 184 patients in each group. The impact of fresh versus frozen-thawed embryo transfer on reproductive outcomes in elderly DOR patients was analyzed. Results:1) There were no statistically significant differences in general data, ovarian stimulation, and laboratory parameters of embryos between the two groups after PSM (all P>0.05). 2) The clinical pregnancy rate [23.91% (44/184)], the implantation rate [16.55% (48/290)], the ongoing pregnancy rate [16.85% (31/184)], and the live birth rate [16.30% (30/184)] in group A were significantly higher than those in group B [14.67% (27/184), P=0.025; 10.27% (30/292), P=0.026; 9.78% (18/184), P=0.046; 9.24% (17/184), P=0.042], with statistically significant differences. There were no statistically significant differences in miscarriage rate, multiple pregnancy rate, preterm birth rate, gestational age at delivery, and neonatal birth weight between the two groups (all P>0.05). 3) After controlling for confounding factors, frozen-thawed embryo transfer, female age, and the number of transferred quality embryos were independent factors influencing clinical pregnancy ( OR=0.486, 95% CI: 0.275-0.858, P=0.013; OR=0.761, 95% CI: 0.686-0.844, P<0.001; transferring one high-quality embryo OR=5.213, 95% CI: 1.501-18.105, P=0.009; transferring two high-quality embryos OR=8.144, 95% CI: 2.072-32.009, P=0.003) and live birth ( OR=0.468, 95% CI: 0.240-0.916, P=0.027; OR=0.733, 95% CI: 0.645-0.834, P<0.001; transferring one high-quality embryo OR=5.457, 95% CI: 1.218-24.448, P=0.027; transferring two high-quality embryos OR=5.900, 95% CI: 1.132-30.754, P=0.035). 4) After controlling for confounding factors, in transfer cycles of patients older than 40 years, the clinical pregnancy rate in group A [14.46% (12/83)] was significantly higher than that in group B [4.88% (4/82)], with a statistically significant difference ( OR=0.285, 95% CI: 0.086-0.946, P=0.040). In single cleavage-stage embryo transfer cycles, the clinical pregnancy rate [21.79% (17/78)] and the live birth rate [16.67% (13/78)] in group A were significantly higher than those in group B [9.21% (7/76), OR=0.311, 95% CI: 0.113-0.857, P=0.024; 6.58% (5/76), OR=0.468, 95% CI: 0.24-0.916, P=0.027], with both statistically significant differences. In cycles with transfer of only one high-quality embryo, the clinical pregnancy rate [27.66% (26/94)] and the live birth rate [20.21% (19/94)] in group A were significantly higher than those in group B [13.54% (13/96), OR=0.347, 95% CI: 0.157-0.765, P=0.009; 10.42% (10/96), OR=0.407, 95% CI: 0.171-0.968, P=0.042], with both statistically significant differences. Conclusion:Fresh cycle embryo transfer can achieve better reproductive outcomes in elderly women with DOR, especially in patients older than 40 years, in single cleavage-stage embryo transfer cycles, or when only one high-quality embryo is available. Fresh cycle embryo transfer should be prioritized in these situations.
6.Effects of vitamin D deficiency on IVF-ET pregnancy outcomes in women with PCOS and normal ovarian reserve
Jingjing XING ; Yan YUE ; Rong LI ; Fuqing ZHANG ; Min LIU ; Xinxiang MA
Chinese Journal of Reproduction and Contraception 2025;45(2):142-153
Objective:To investigate the impact of vitamin D deficiency on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with polycystic ovary syndrome (PCOS) and normal ovarian reserve (NOR). Methods:A retrospective cohort study was conducted on infertile women undergoing their first IVF-ET cycle in the Department of Reproductive Genetics, Zhengzhou Maternity and Child Health Care Hospital from January 2018 to December 2023, including 318 PCOS patients (group P) and 528 NOR patients (group N). Each group was divided into three subgroups according to serum 25-hydroxyvitamin D [25(OH)D] levels: severe deficiency [25(OH)D<12 μg/L], deficiency [12 μg/L≤25(OH)D<20 μg/L], and non-deficiency [25(OH)D≥20 μg/L]. The impact of vitamin D deficiency on pregnancy outcomes was analyzed in each group. 1∶1 propensity score matching was applied to match the baseline characteristics between group P and group N , resulting in 158 matched cases of PCOS (group P) and NOR (group N). Pregnancy outcomes were compared between the two groups under the same vitamin D status.Results:1) Among PCOS patients, there were no significant differences in general characteristics and pregnancy outcomes among the three subgroups (all P>0.05). The two pronuclei (2PN) rate in the severe deficiency subgroup [59.93% (721/1 203)] was significantly lower than that in the deficiency subgroup [63.70% (1 032/1 620)], with a statistically significant difference ( P=0.045), and both were lower than that in the non-deficiency subgroup [68.06% (554/814)], with a statistically significant difference ( P<0.001, P=0.037). There were no statistically significant differences in the number of oocytes retrieved and MⅡ oocytes, MⅡ oocyte rate, 2PN number, 2PN rate, cleavage number, cleavage rate, number of available embryos on day 3 (day 3, D3), number of high-quality embryos on D3, D3 high-quality embryo rate, clinical pregnancy rate, embryo implantation rate, early miscarriage rate, live birth rate, and premature birth rate among subgroups (all P>0.05). Female age ( OR=0.930, 95% CI: 0.871-0.992, P=0.028), endometrial thickness on the day of transfer ( OR=0.877, 95% CI: 0.791-0.971, P=0.012), number of D3 high-quality embryos ( OR=1.135, 95% CI: 1.050-1.228, P=0.001), and ovulation stimulating protocol ( OR=2.230, 95% CI: 1.153-4.314, P=0.017) were independent factors influencing clinical pregnancy. 2) Among NOR patients, there were no significant differences in general characteristics, pregnancy outcomes, laboratory parameters, or other outcome-related indices among the three subgroups (all P>0.05). Female age ( OR=0.944, 95% CI: 0.900-0.990, P=0.018), number of D3 high-quality embryos ( OR=1.070, 95% CI: 1.004-2.597, P=0.037), and number of transferred embryos ( OR=1.753, 95% CI: 1.184-2.597, P=0.005) were independent factors influencing clinical pregnancy. 3) After matching, there were no significant differences in baseline characteristics and pregnancy outcomes between group P and group N (all P>0.05). In the severe vitamin D deficiency state, group P had significantly lower MⅡ oocyte rate [76.64% (525/685)], 2PN rate [59.69% (345/578)], embryo implantation rate [35.71% (30/84)], and live birth rate [34.00% (17/50)] compared with group N [81.58% (465/570), P=0.033; 67.00% (335/500), P=0.013; 51.28% (40/78), P=0.046; 55.32% (26/47), P=0.035]. In the vitamin D deficiency state, the 2PN rate in group P [66.50% (532/800)] was significantly lower than that in group N [72.00% (725/1 007), P=0.012]. Conclusion:Vitamin D deficiency may adversely affect IVF-ET outcomes in patients with PCOS, with more pronounced effects in cases of severe deficiency. However, it has no impact on the assisted reproductive outcomes in NOR patients.
7.Impact of fresh and frozen-thawed embryo transfer on pregnancy outcomes in elderly women with DOR
Jingjing XING ; Zheng WANG ; Rong LI ; Li LI
Chinese Journal of Reproduction and Contraception 2025;45(6):591-599
Objective:To investigate the impact of fresh and frozen-thawed embryo transfer on pregnancy outcomes in patients with diminished ovarian reserve (DOR) at an advanced age.Methods:Using a retrospective cohort study design, we enrolled elderly women with DOR who underwent their first in vitro fertilization and embryo transfer (IVF-ET) treatment at Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital between January 2018 and December 2022. Patients were grouped according to the cycle type of their first embryo transfer: a fresh cycle transfer group (group A, n=563) and a frozen-thawed cycle transfer group (group B, n=234). Propensity score matching (PSM, 1∶1) was used to match the baseline characteristics and embryo transfer information of the two groups, resulting in 184 patients in each group. The impact of fresh versus frozen-thawed embryo transfer on reproductive outcomes in elderly DOR patients was analyzed. Results:1) There were no statistically significant differences in general data, ovarian stimulation, and laboratory parameters of embryos between the two groups after PSM (all P>0.05). 2) The clinical pregnancy rate [23.91% (44/184)], the implantation rate [16.55% (48/290)], the ongoing pregnancy rate [16.85% (31/184)], and the live birth rate [16.30% (30/184)] in group A were significantly higher than those in group B [14.67% (27/184), P=0.025; 10.27% (30/292), P=0.026; 9.78% (18/184), P=0.046; 9.24% (17/184), P=0.042], with statistically significant differences. There were no statistically significant differences in miscarriage rate, multiple pregnancy rate, preterm birth rate, gestational age at delivery, and neonatal birth weight between the two groups (all P>0.05). 3) After controlling for confounding factors, frozen-thawed embryo transfer, female age, and the number of transferred quality embryos were independent factors influencing clinical pregnancy ( OR=0.486, 95% CI: 0.275-0.858, P=0.013; OR=0.761, 95% CI: 0.686-0.844, P<0.001; transferring one high-quality embryo OR=5.213, 95% CI: 1.501-18.105, P=0.009; transferring two high-quality embryos OR=8.144, 95% CI: 2.072-32.009, P=0.003) and live birth ( OR=0.468, 95% CI: 0.240-0.916, P=0.027; OR=0.733, 95% CI: 0.645-0.834, P<0.001; transferring one high-quality embryo OR=5.457, 95% CI: 1.218-24.448, P=0.027; transferring two high-quality embryos OR=5.900, 95% CI: 1.132-30.754, P=0.035). 4) After controlling for confounding factors, in transfer cycles of patients older than 40 years, the clinical pregnancy rate in group A [14.46% (12/83)] was significantly higher than that in group B [4.88% (4/82)], with a statistically significant difference ( OR=0.285, 95% CI: 0.086-0.946, P=0.040). In single cleavage-stage embryo transfer cycles, the clinical pregnancy rate [21.79% (17/78)] and the live birth rate [16.67% (13/78)] in group A were significantly higher than those in group B [9.21% (7/76), OR=0.311, 95% CI: 0.113-0.857, P=0.024; 6.58% (5/76), OR=0.468, 95% CI: 0.24-0.916, P=0.027], with both statistically significant differences. In cycles with transfer of only one high-quality embryo, the clinical pregnancy rate [27.66% (26/94)] and the live birth rate [20.21% (19/94)] in group A were significantly higher than those in group B [13.54% (13/96), OR=0.347, 95% CI: 0.157-0.765, P=0.009; 10.42% (10/96), OR=0.407, 95% CI: 0.171-0.968, P=0.042], with both statistically significant differences. Conclusion:Fresh cycle embryo transfer can achieve better reproductive outcomes in elderly women with DOR, especially in patients older than 40 years, in single cleavage-stage embryo transfer cycles, or when only one high-quality embryo is available. Fresh cycle embryo transfer should be prioritized in these situations.
8.Role of hippocampal activating transcription factor 5 in cognitive impairment induced by neuropathic pain in mice: relationship with mitochondrial unfolded protein response
Fei XING ; Xiaoshan SHI ; Yaowei XU ; Xin WEI ; Mingcui QU ; Dan CHENG ; Jingjing YUAN ; Zhongyu WANG ; Na XING ; Yanna LI
Chinese Journal of Anesthesiology 2025;45(3):329-334
Objective:To evaluate the role of hippocampal activating transcription factor 5 (ATF5) in cognitive impairment induced by neuropathic pain and the relationship with mitochondrial unfolded protein response(mtUPR) in mice.Methods:This study was conducted in 2 parts. Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups ( n=12 each) using a random number table method: sham operation group (S1 group) and neuropathic pain group (NP group). Neuropathic pain was induced by chronic constriction injury to the sciatic nerve. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model and at 7, 14, 21 and 28 days after developing the model. Mouse cognitive function was assessed using the novel object recognition test from 30-31 days after developing the model. After the end of the novel object recognition test, mice were sacrificed and the hippocampal CA1 region was harvested for determination of the expression of ATF5 (by Western blot) and the expression of ATF5 in neurons, microglia and astrocytes (by immunofluorescence double staining). Experiment Ⅱ Thirty-six SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S2 group), neuropathic pain + ATF5 up-regulation group (NA group), and neuropathic pain + empty virus group (NE group). On day 14 after developing the model, a virus that specifically up-regulated ATF5 expression in neurons and empty virus were injected into the hippocampal CA1 region. The MWT and TWL were measured at days 28 and 35 after developing the model. The novel object recognition test was performed on day 36 after developing the model to evaluate the cognitive function. After the end of the behavioral test, mice were sacrificed and the hippocampal CA1 region was harvested for detection of the expression of ATF5 and mtUPR marker proteins (Lon protease [LONP1] and heat shock protein 60 [HSP60]) by Western blot. Results:Experiment Ⅰ Compared with S1 group, no statistically significant change was found in the MWT and TWL before developing the model ( P>0.05), the MWT and TWL were significantly decreased on days 7, 14, 21 and 28 after developing the model, the discrimination index (DI) was decreased at day 31 after developing the model, the expression of ATF5 was down-regulated, the expression of ATF5 in neurons was down-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF5 in mircrolia and astrocytes in NP group ( P>0.05). Experiment Ⅱ Compared with S2 group, the MWT and TWL were significantly decreased on days 28 and 35 after developing the model in NE group and NA group, DI was decreased, and the expression of ATF5, LONP1 and HSP60 was down-regulated in NE group ( P<0.05), and no significant change was found in NA group ( P>0.05). Compared with NE group, no significant change was found in the MWT and TWL in NA group ( P>0.05), DI was significantly increased, and the expression of ATF5, LONP1 and HSP60 was up-regulated in NA group ( P<0.05). Conclusions:Down-regulated ATF5 in the hippocampus is involved in the process of cognitive impairment caused by neuropathic pain, and the mechanism may be related to the inhibition of mtUPR.
9.A meta-analysis of risk factors for internalizing problems in adolescents
Jingjing ZHAO ; Kun WANG ; Ye LI ; Rong BAI ; Shufen XING
Chinese Mental Health Journal 2024;38(2):114-121
Objective:To analyze the risk factors of internalizing problems in adolescents aged 12 to 18 years,and provide supporting evidence for the scientific prevention and effective control of internalizing problems in adolescents.Methods:By systematically searching the Chinese and English databases such as CNKI,VIP,Wan-fang,PubMed,Web of Science,Psychology and Behavioral Sciences Collection,PsycInfo,PsycArticles and ERIC,literature on risk factors of internalizing problems among adolescents in the past 22 years was collected,and non-clinical literature using CBCL or YSR or TRF scales to measure related internalizing problems were included.Meta analysis was performed using CMA3.0,with r as the effect size indicator and random effects model combined with the effect size of risk factors.Results:Finally,77 and 18 risk factors literatures were included,including 7 risk fac-tors of individuals,7 risk factors of family,and 4 risk factors of school/community.The average correlation between family risk factors and internalizing problems of adolescents was the highest.Among family risk factors,parent-child attachment had the highest correlation.Conclusion:Individual risk factors,family risk factors and school/com-munity risk factors are significantly positively correlated with adolescent internalizing problems,and family risk fac-tors(especially parent-child attachment quality)have the highest correlation with adolescent internalizing problems.
10.Clinical progress in the diagnosis and treatment of end-stage liver disease complicated with acute kidney injury
Jingjing LU ; Yangyang HU ; Xing ZHANG ; Yue LUO ; Yadong WANG ; Caiyan ZHAO
Chinese Journal of General Practitioners 2024;23(3):314-319
Acute kidney injury (AKI) is a devastating complications of end-stage of liver disease (ESLD), seriously affecting the prognosis of patients. With the deepening understanding of the pathogenesis, the definition, staging, diagnosis and treatment of ESLD with AKI have been gradually optimized. This article reviews the evolution of definition, pathogenesis, diagnosis and treatment of ESLD with AKI, to provide reference for early recognition, precise diagnosis and standardized treatment of this condition.

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