Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

ObjectiveTo analyze the quantity-quality transfer of standard decoction of Ginseng Radix et Rhizoma（GRR） decoction pieces produced by fresh and traditional cutting， and to provide reference for quality control and application development of the decoction pieces produced by fresh cutting. MethodTen batches of representative GRR decoction pieces produced by fresh and traditional cutting and their standard decoctions were prepared by standard process， and high performance liquid chromatography（HPLC） fingerprint of the standard decoction was established and performed on an Agilent EC-C₁₈ column（4.6 mm×150 mm， 2.7 μm） with acetonitrile（A）-0.1% phosphoric acid aqueous solution（B） as the mobile phase for gradient elution（0-23 min， 18%-21%A； 23-35 min， 21%-28%A； 35-80 min， 28%-32%A）， and the detection wavelength was 203 nm. Then similarity evaluation， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） of fingerprint of the standard decoction were performed to screen the differential components with variable importance in the projection（VIP） value>1. Quantitative analysis was carried out on the screened known differential components， and combined with the indicators of the dry extract rate and the transfer rate， to explore the differences in the quantity-quality transfer between the standard decoction of GRR decoction pieces produced by fresh and traditional cutting. ResultThe fingerprint similarity of the standard decoction of GRR decoction pieces produced by fresh and traditional cutting was more than 0.950， and 18 common peaks were identified， including 9 identified common peaks. The results of PCA and PLS-DA showed that there were some differences in the contents of index components between the two standard decoctions. The contents of ginsenoside Rg₁， Re and Ro in GRR decoction pieces produced by fresh cutting were higher than those in traditional decoction pieces， while the contents of ginsenoside Rb₁， Rc ， Rb₂ and Rd were lower than those in traditional decoction pieces. The contents of ginsenoside Rg₁， Re， Rb₁ and Ro in the standard decoction of GRR decoction pieces produced by fresh cutting were higher than those in the standard decoction of traditional decoction pieces， while the contents of ginsenoside Rc ， Rb₂ and Rd were comparable between the two standard decoctions. Compared with the standard decoction of the traditional decoction pieces， the average transfer rates of ginsenoside Rg₁， Rb₁， Rc， Rb₂ and dry extract rate of the standard decoction of GRR decoction pieces produced by fresh cutting were significantly increased（P<0.05）， and the average transfer rate of ginsenoside Re and Rd also increased， but the difference was not statistically significant. ConclusionThe dry extract rate， content and transfer rate of index components of standard decoction of GRR decoction pieces produced by fresh cutting are better than those of the standard decoction of traditional decoction pieces， which can provides data support for the subsequent clinical application of fresh cutting products.

Objective To investigate the effects of different doses of chronic nicotine exposure on the pathology of Alzhei-mer's disease(AD),to clarify the effects of nicotine on cognitive function and related pathology in AD model mice,and to pro-vide laboratory evidence for clinical prevention and intervention of AD.Methods Nine-month-old triple-transgenic(3 × Tg)mice(APPswe,PS1M146V,and Tau P301L transgenes)were treated with low(5％,50 μg/mL),medium(10％,100 μg/mL)and high(20％,200 μg/mL)doses of nicotine for 3 months.Western blot,immunofluorescence and qPCR were used to detect amyloid be-ta(Aβ)pathology,Tau phosphorylation,synaptic damage and neuroinflammation in different groups of mice.Microglia was co-stained with Aβ to show the phagocytosis of plaques.Behavioral test was used to detect the cognitive learning ability of experi-mental mice.Results Administration of high dosage of nicotine over the course of three consecutive months resulted in an aug-mentation in Aβ plaques,while the utilization of low dosage of nicotine for an equivalent period yields a mitigating influence on Aβ accumulation and effectively alleviated synaptic impairments within the hippocampus.Moreover,chronic exposure of high nicotine exacerbated both microglial activation and neuroinflammation,along with astrogliosis in the brains of 3 X Tg mice,whereas the administration of low dosage of nicotine exhibited no discernible impact.Chronic exposure to different doses of nico-tine had no significant effect on Tau phosphorylation and cognitive behaviors in mice.Conclusion Chronic exposure to low dose nicotine alleviates Aβ accumulation and brain synaptic damage in AD model mice.Chronic exposure to high dose nicotine aggra-vates Aβ deposition and neuroinflammation.

Objective To investigate the effects of different doses of chronic nicotine exposure on the pathology of Alzhei-mer's disease(AD),to clarify the effects of nicotine on cognitive function and related pathology in AD model mice,and to pro-vide laboratory evidence for clinical prevention and intervention of AD.Methods Nine-month-old triple-transgenic(3 × Tg)mice(APPswe,PS1M146V,and Tau P301L transgenes)were treated with low(5％,50 μg/mL),medium(10％,100 μg/mL)and high(20％,200 μg/mL)doses of nicotine for 3 months.Western blot,immunofluorescence and qPCR were used to detect amyloid be-ta(Aβ)pathology,Tau phosphorylation,synaptic damage and neuroinflammation in different groups of mice.Microglia was co-stained with Aβ to show the phagocytosis of plaques.Behavioral test was used to detect the cognitive learning ability of experi-mental mice.Results Administration of high dosage of nicotine over the course of three consecutive months resulted in an aug-mentation in Aβ plaques,while the utilization of low dosage of nicotine for an equivalent period yields a mitigating influence on Aβ accumulation and effectively alleviated synaptic impairments within the hippocampus.Moreover,chronic exposure of high nicotine exacerbated both microglial activation and neuroinflammation,along with astrogliosis in the brains of 3 X Tg mice,whereas the administration of low dosage of nicotine exhibited no discernible impact.Chronic exposure to different doses of nico-tine had no significant effect on Tau phosphorylation and cognitive behaviors in mice.Conclusion Chronic exposure to low dose nicotine alleviates Aβ accumulation and brain synaptic damage in AD model mice.Chronic exposure to high dose nicotine aggra-vates Aβ deposition and neuroinflammation.

Objective:The study aimed to investigate the effects of exercise on the expression of ferroptosis-related proteins and the associated mechanisms in a post-traumatic stress disorder(PTSD)model induced by transient foot shock.Methods:Thirty-five male C57BL/6J mice(8 weeks old)were randomly divided into three groups:Control group,PTSD group,and Exe+PTSD group.PTSD model mice were established by foot-shock and PTSD behaviors were assessed using a fear conditioning box.Iron distribution areas were detected by Fe3+staining.Western Blot analysis were performed to determine the expression level of ferroptosis-related proteins in the mice.Results:Compared to the control group,the freezing time and Fe3+distribution areas in the cortex and hippocampus were significantly increased in the mice with PTSD(P＜0.05).The levels of ferroportin1(FPN1),glutathione peroxidase 4(GPX4),and brain-derived neurotrophic factor(BDNF)proteins were significantly decreased(P＜0.05),while the expression of high mobility group box 1(HMGB1)protein was significantly elevated(P＜0.05).Exercise significantly reduced freezing time and Fe3+accumulation in the cortex and hippocampus(P＜0.05),and it also up-regulated the expression of FPN1,GPX4,and BDNF proteins(P＜0.05),while down-regulating HMGB1 expression compared to the PTSD group(P＜0.05).Conclusion:This study demonstrates that PTSD induces the ferroptosis-related pathway in mice,and exercise can inhibit iron accumulation and reverse the expression of ferroptosis-related proteins induced by PTSD,there-by alleviating PTSD-like behavior in mice.

OBJECTIVE To establish the grade s tandard for Panax quinquefoli um and to evaluate the quality of different grades of medicinal materials. METHODS Totally 24 batches of P. quinquefolium were used as test samples. Pearson correlation analysis method was used to analyze the correlation between qualitative analysis indicators （taproot length ，taproot diameter and weight of single root ）and internal component indicators （ethanol-soluble extract ，and the contents of ginsenoside Rg 1，ginsenoside Re ， ginsenoside Rb 1，ginsenoside Rc ，ginsenoside Rb 2，ginsenoside Rd ，pseudo-ginsenoside F 11）. Combined with chemometrics methods，the reference indexes for the classification of P. quinquefolium were selected ，and the classification standards were formulated. HPLC-ELSD fingerprints of 24 batches of P. quinquefolium were established and their similarity evaluation was also performed. The chromatographic peaks were identified by comparison with the reference substance ，and then the quality of different grades of P. quinquefolium was evaluated by cluster analysis. RESULTS After screening ，taproot diameter ，the weight of single root and the content of ginsenoside Rd were taken as the reference indexes for the classification of P. quinquefolium . According to above 3 indexes，P. quinquefolium were divided into 3 grades：special grade ，first grade and second grade. According to the center value of K-means clustering ，the total score of special-grade medicinal materials was more than 135.40，that of first-grade medicinal materials was 61.82-135.40，and that of second-grade medicinal materials was less than 61.82. In the HPLC-ELSD fingerprints of 24 batches of P. quinquefolium ，25 common peaks were confirmed ，and 7 characteristic peaks were identified. The similarity of the chromatograms of P. quinquefolium of special grade ，first grade and second grade with fingerprints ranged 0.980-0.989，0.962-0.968，0.940-0.949，respectively. The results of cluster analysis showed that different grades of P. quinquefolium could be identified significantly. CONCLUSIONS The grade standard and HPLC-ELSD fingerprints of P. quinquefolium are established，which can be applied for exclusive identification of P. quinquefolium ，and provide reference for its quality control and grade classification.

Objective    To compare the effect on postoperative immune function between da Vinci robot-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) , and to provide clinical support for more effective surgical procedures. Methods    A total of 90 patients undergoing radical resection of pulmonary carcinoma in our hospital from June to November 2019 were included. There were 49 males and 41 females with an average age of 62.67 (37-84) years. Among them, 50 patients underwent da Vinci robot-assisted thoracoscopic surgery (a RATS group) and 40 patients underwent video-assisted thoracoscopic surgery (a VATS group). The perioperative indexes as well as postoperative inflammatory factors and immune level effects between the two groups were compared. Results    Compared with the VATS, RATS could significantly shorten the operation time and decrease intraoperative blood loss (P<0.05). RATS also effectively reduced the increase of postoperative inflammatory factor level (P<0.05). But there was no significant difference in postoperative immune function between the RATS group and the VATS group (P>0.05). Conclusion    RATS is superior to VATS in the treatment of non-small cell lung cancer in perioperative indicators and inflammatory factors.

Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.

Objective    To compare the the effectiveness of robot-assisted thoracic surgery (RATS) with video-assisted thoracic surgery (VATS), in stageⅠ lung adenocarcinoma. Methods    From January 2012 to December 2018, 291  patients were included. The patients were allocated into two groups including a RATS group with 125 patients and a VATS group with 166 patients. Two cohorts (RATS, VATS ) of clinical stageⅠ lung adenocarcinoma patients were matched by propensity score. Then there were 114 patients in each group (228 patients in total). There were 45 males and 69 females at age of 62±9 years in the RATS group; 44 males, 70 females at age of 62±8 years in the VATS group. Overall survival (OS) and disease-free survival (DFS) were assessed. Univariate and multivariate analyses were performed to identify factors associated with the outcomes. Results     Compared with the VATS group, the RATS group got less blood loss (P<0.05) and postoperative drainage (P<0.05) with a statistical difference. There was no statistical difference in drainage time (P>0.05) or postoperative hospital stay (P>0.05) between the two groups. The RATS group harvested more stations and number of the lymph nodes with a statistical difference (P<0.05). There was no statistical difference in 1-year, 3-year and 5-year OS and mean survival time (P>0.05). While there was a statistical difference in DFS between the two groups (1-year DFS: 94.1% vs. 95.6%; 3-year DFS: 92.6% vs. 75.2%; 5-year DFS: 92.6% vs. 68.4%, P<0.05; mean DFS time: 78 months vs. 63 months, P<0.05) between the two groups. The univariate analysis found that the number of the lymph nodes dissection was the prognostic factor for OS, and tumor diameter, surgical approach, stations and number of the lymph nodes dissection were the prognostic factors for DFS. However, multivariate analysis found that there was no independent risk factor for OS, but the tumor diameter and surgical approach were independently associated with DFS. Conclusion    There is no statistical difference in OS between the two groups, but the RATS group gets better DFS.