1.Effects of Shujin Jiannao Formula (舒筋健脑方) on Neural Repair and PI3K-Akt-mTOR Pathway of Brain Tissue in Cerebral Palsy Model Rats
Ruiqin YU ; Yanjun MO ; Houjun ZHANG ; Gang LIU ; Zhuoluo ZHOU ; Zechen RUAN ; Lin XU ; Xiaohong MU
Journal of Traditional Chinese Medicine 2025;66(10):1038-1045
ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula (舒筋健脑方) for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group, model group, and Shujin Jiannao Formula group, with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling, rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/(kg·d) by gavage, while the normal group and model group were given normal saline 10 ml/(kg·d) by gavage once a day. After one week of intervention, the rats' body weight was measured, and Zea-Longa scores, the righting reflex test, and the hindlimb suspension test were conducted for assessment; hematoxylin-eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissue, and the number of Nissl-positive neurons was counted; enzyme-linked immunosorbent assay (ELISA) was employed to measure levels of inflammatory cytokines in the brain tissue, specifically interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); immunofluorescence was used to detect the expression levels of neurofilament protein 200 (NF200) and myelin basic protein (MBP) in brain tissue; Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt/PKB/Rac), and mammalian target of rapamycin (mTOR) in brain tissue. ResultsCompared with the normal group, rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test (P<0.01); pathological findings revealed loose structure in the cerebral cortex, hippocampal atrophy, and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated, and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced, and immunofluorescence intensity of NF200 and MBP, as well as protein expression levels of PI3K and mTOR, significantly decreased (P<0.05 or P<0.01). Compared with the model group, rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores (P<0.05); pathological damage in brain tissue alleviated, levels of IL-1β and TNF-α reduced, the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased, and the immunofluorescence intensity of NF200 and MBP, as well as the protein levels of PI3K and mTOR, significantly elevated (P<0.05 or P<0.01). There were no statistically significant differences among the groups in body weight, body-turning time, or AKT protein levels in brain tissue (P>0.05). ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy, exert neurorestorative effects, and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.
2.Severe cardiotoxic characteristics associated with allogeneic hematopoietic stem cell transplantation preconditioning in patients with aplastic anemia
Xue MING ; Yuanyuan ZHANG ; Tingting HAN ; Jingzhi WANG ; Xiaodong MO ; Fengrong WANG ; Chenhua YAN ; Yu WANG ; Yuhong CHEN ; Zhengli XU ; Feifei TANG ; Ting ZHAO ; Kaiyan LIU ; Xiaohui ZHANG ; Xiaojun HUANG ; Lanping XU
Chinese Journal of Internal Medicine 2024;63(11):1096-1103
Objective:To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA).Methods:This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People′s Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method.Results:In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n=26). Most patients ( n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions:Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.
3.Status quo of psychological contracts among members of the“1+N”family doctor teams in Shenzhen and the impact on job burnout
Shuangshuang WEN ; Yue DU ; Mulan JIANG ; Liangyu HUANG ; Qihua MO ; Ye LIU ; Jianwei ZHANG ; Hegao YU ; Liang MA
Chinese Journal of General Practitioners 2024;23(8):848-854
Objective:To investigate the status quo of psychological contracts and influencing factors among members of the "1+N" family doctor teams in Shenzhen and to explore the impact of psychological contracts on job burnout.Methods:This cross-sectional study was conducted from September 30 to October 31, 2022 among 361 members of 92 family doctor teams from 92 community health service centers which provided family doctor team service in Shenzhen city. A self-designed general information questionnaire, an employee psychological contract questionnaire (including organizational responsibility and personal responsibility dimensions), and a job burnout scale (including emotional exhaustion, depersonalization, and personal accomplishment dimensions) were used in the study. T-tests, one-way ANOVA, Pearson correlation analysis, and multiple linear regression analysis were used to analyze the influencing factors of psychological contracts and job burnout.Results:Among 361 respondents, there were 299 females (82.8%) and 62 males (17.2%), and a higher proportion of general practitioners (37.5%, 129/361) and nurses (41.8%, 151/361). The total score of psychological contracts among the 361 respondents was (141.6±19.5), with organizational responsibility scoring (70.6±11.2) and personal responsibility scoring (71.0±9.3). On the job burnout scale, emotional exhaustion scored (17.89±6.82), depersonalization scored (6.51±2.54), and personal accomplishment scored (30.95±5.70). General practitioners scored lower in organizational responsibility and personal responsibility compared to other members ( F=7.341,3.119, all P<0.05), and higher in emotional exhaustion and depersonalization ( F=7.637, 2.415, all P<0.05). Members with≤5 years of work experience scored lower in personal responsibility and personal accomplishment ( F=3.656, 4.205, all P<0.05). Correlation analysis showed that scores of organizational responsibility and personal responsibility were negatively correlated with levels of emotional exhaustion and depersonalization ( r=-0.618, -0.526, all P<0.01), ( r=-0.404, -0.393, all P<0.01), and positively correlated with personal accomplishment ( r=0.500, 0.558, all P<0.01). Multiple linear regression analysis indicated that organizational responsibility negatively affected emotional exhaustion and depersonalization ( β=-0.554, -0.274, all P<0.01), and positively affected personal accomplishment ( β=0.172, P<0.05). Personal responsibility positively affected personal accomplishment ( β=0.404, P<0.01). Conclusions:The study demonstrates that general practitioners in family doctor teams in Shenzhen city have lower psychological contract levels and are more prone to emotional exhaustion and depersonalization; members with≤5 years of work experience have lower personal responsibility and accomplishment. The results indicate that enhancing organizational responsibility can reduce job burnout of members in family doctor teams.
4.Comparison of suction blister transplantation and noncultured autologous suspension of epidermal cells in treatment of stable vitiligo in the face and neck region
Yong TAO ; Zhifei LIU ; Mingzi ZHANG ; Xiaohan HU ; Nanze YU ; Fei LONG ; Zenan XIA ; Lan MO ; Xiaojun WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(3):208-212
Objective:To evaluate the differences and aesthetic meaning of stable vitiligo treatment in the face and neck region using suction blister transplantation or noncultured autologous suspension of epidermal cells.Methods:Sixty-four stable vitiligo patients (25 males and 39 females with age ranges from 10 to 46 years, average 25 years) in the face and neck region were randomly divided into two groups (32 patients in each group): one group received suction blister transplantation, while other group received noncultured autologous suspension of epidermal cells. Patients′treatment effectiveness, pigmentation and piecing deformity were evaluated in postoperative 3 months and 6 months.Results:In the postoperative 3 months and 6 months, the effectiveness of suction blister transplantation group was 68.75% (22/32) and 90.63% (29/32), respectively, while the effectiveness of noncultured autologous suspension of epidermal cells group was 59.37% (19/32) and 87.50% (28/32), respectively, in which no significant differences were found between two groups ( P>0.05). No obvious pigmentation and piecing deformity were found in noncultured autologous suspension of epidermal cells group, which were much better than the suction blister transplantation group in postoperative 3 months and 6 months. Conclusions:Both suction blister transplantation and noncultured autologous suspension of epidermal cells could bring good treatment effectiveness for patients of stable vitiligo in the face and neck region. Compared with suction blister transplantation, noncultured autologous suspension of epidermal cells could offer better aesthetic appearance.
5.Summary of the 19 th Chinese Symposium of Burns and Wounds
Yanling LYU ; Yu MO ; Guangping LIANG ; Gaoxing LUO ; Yizhi PENG ; Dan SUN ; Kaizhen QIU ; Luyao WU ; Tingting LI ; Zhixin LIU
Chinese Journal of Burns 2024;40(7):699-700
The 19 th Chinese Symposium of Burns and Wounds was successfully held in Foshan of Guangdong Province from June 20 th to 22 nd in 2024. There were more than 700 delegates attending the academic event. The theme of the congress was expansion, integration and standardization, which could promote academic exchanges, multi-disciplinary fusion, and standardization of clinical treatment of burns and wounds. A total of nearly 200 famous experts and scholars had their speeches on the two-day keynote forum and special academic seminars including critical care, wound repair, scar prevention and treatment, rehabilitation nursing, and disciplinary integration sessions. The congress ended successfully with abundant fruits and friendship.
6.Causes and characteristics of pre-engraftment mortality after allogeneic hematopoietic stem cell transplantation
Jing LIU ; Meng LYU ; Yuanyuan ZHANG ; Xiaodong MO ; Yuqian SUN ; Chenhua YAN ; Yu WANG ; Lanping XU ; Xiaohui ZHANG ; Kaiyan LIU ; Xiaojun HUANG
Chinese Journal of Hematology 2024;45(6):542-548
Objective:To analyze the causes and demographic characteristics of pre-engraftment mortality in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and investigate the risk factors and measures for preventing pre-engraftment mortality.Methods:A retrospective case analysis, involving a total of 7 427 patients who underwent allo-HSCT at Peking University People’s Hospital between January 2016 and July 2023, was conducted.Results:Among the 7 427 patients who underwent allo-HSCT, 56 cases (0.75% ) experienced pre-engraftment mortality. The median time to death for these 56 patients was +7 (-3 to +38) days after stem cell infusion. The median times to death for patients with acute leukemia (AL), severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS) were +11 (-1 to +38), +3 (-1 to +34), and +16 (-1 to +38) days, respectively ( P=0.013). The main causes of pre-engraftment mortality were infection (39.3% ), cardiac toxicity (28.6% ), and intracranial hemorrhage (26.8% ). Infection was the most common cause of pre-engraftment mortality in patients with AL and MDS (55.0% and 60.0% ), whereas cardiac toxicity was predominantly observed in patients with SAA (71.4% ), with no cases in patients with AL and only one case in patients with MDS. Among patients who died from intracranial hemorrhage, 53.3% had severe infections. The median times to death for infection, cardiac toxicity, and intracranial hemorrhage was +11 (-1 to +38), +2.5 (-1 to +17), and +8 (-3 to +37) days, respectively ( P<0.001) . Conclusions:Infection is the primary cause of pre-engraftment mortality in allo-HSCT, and severe cardiac toxicity leading to pre-engraftment mortality should be closely monitored in patients with SAA.
7.Clinical characteristics of human parvovirus B19 infection after allogeneic stem cell transplantation
Jin ZHANG ; Rui MA ; Xueyi LUO ; Xiaohui ZHANG ; Lanping XU ; Yu WANG ; Xiaodong MO ; Meng LYU ; Kaiyan LIU ; Xiaojun HUANG ; Yuqian SUN
Chinese Journal of Hematology 2024;45(6):591-593
Human parvovirus B19 (HPVB19) belongs to Parvoviridae, a genus of erythrovirus, and has been associated with various human diseases, and HPVB19 infection is one of the most important causes of refractory anemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study retrospectively analyzed 24 patients with HSCT combined with HPVB19 infection to collate and summarize the clinical presentation, treatment, and regression of patients with combined HPVB19 infection after allo-HSCT and provide experience in the management of HPVB19 infection after allo-HSCT. The median age of the patients with HPVB19 infection was 25 years, and the median time of infection occurrence was +107 days after transplantation, and 22 (91.7% ) had anemia with a median hemoglobin (HGB) level of 77.5 (46-149) g/L, and 13 (54.2% ) had new-onset anemia or persistent decline in HGB. The median length of hospital stay was 19 days. Among patients with new-onset anemia or persistent decline in HGB, the mean increase in HGB after treatment with intravenous immunoglobulin and/or antiviral therapy was 15.69 g/L, and treatment was effective in 10 (76.92% ) patients. HPVB19 infection should be alerted to the development of refractory anemia after HSCT; despite the lack of specific treatment, the overall prognosis of HPVB19-infected patients is good.
8.Prognostic analysis of 8 patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation
Yun HE ; Zhengli XU ; Rui MA ; Jing LIU ; Yuanyuan ZHANG ; Meng LYU ; Xiaodong MO ; Chenhua YAN ; Yuqian SUN ; Xinyu ZHANG ; Yu WANG ; Xiaohui ZHANG ; Xiaojun HUANG ; Lanping XU
Chinese Journal of Hematology 2024;45(9):816-820
Objective:To evaluate the safety of patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A retrospective analysis of the clinical characteristics and prognosis of eight patients with hepatic adenoma who underwent allo-HSCT in the Hematology Department of Peking University People’s Hospital from January 2010 to March 2024 was conducted.Results:Of the eight patients who underwent allo-HSCT with hepatic adenoma, one patient was considered MDS-h transfusion-dependent and seven had aplastic anemia. The median age of the patients was 23 years (13-48 years). The median time from the diagnosis of AA or MDS to transplantation was 14 years (6-24 years), whereas the median time from taking androgens to diagnosing hepatic adenoma was 9 years (5-13 years). Six cases underwent haplo-HSCT, one case underwent matched unrelated donor HSCT, and one case underwent matched related donor HSCT. All patients achieved neutrophil engraftment at a median time of 11.5 days (11-20 days) and PLT engraftment within 60 days at a median of 19 days (10-37 days) after haplo-HSCT. Moreover, seven patients developed CMV anemia after transplantation, three patients had hemorrhagic cystitis, and two patients developed acute GVHD. During and after transplantation, eight patients did not show severe liver function damage or rupture of hepatic adenoma. In relation to imaging size, four patients showed varying degrees of reduction in hepatic adenoma size after transplantation, whereas four patients did not show significant changes in hepatic adenoma size after transplantation. The median follow-up time was 540.5 (30-2 989) days. Of the eight patients, six survived and two died. Furthermore, no direct correlation was observed between death and hepatic adenoma.Conclusion:Patients with hepatic adenomas undergoing allo-HSCT are not contraindications for transplantation, which will not increase transplant-related mortality.
9.Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling
Li BEI ; Zhang YONG ; Liu XINYUAN ; Zhang ZIYANG ; Zhuang SHUQING ; Zhong XIAOLI ; Chen WENBO ; Hong YILIN ; Mo PINGLI ; Lin SHUHAI ; Wang SHICONG ; Yu CHUNDONG
Journal of Pharmaceutical Analysis 2024;14(4):601-614
Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is un-known.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the acti-vation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphory-lation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by acti-vating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.
10.Melatonin alleviates autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage via the PI3K/AKT pathway
Chen-Meng LIU ; Xiao-Tian GAO ; Hai-Mo ZHANG ; Hui-Ning BI ; Chen LIANG ; Jing-Ying JIANG ; Pei-Lun XIAO ; Xiao-He YU ; Xiao-Li WANG
Chinese Journal of Contemporary Pediatrics 2024;26(6):631-638
Objective To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage(HIBD)and to explore its mechanisms via the PI3K/AKT signaling pathway,aiming to provide a basis for the clinical application of melatonin.Methods Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group,an HIBD group,and a melatonin group(n=9 each).The neonatal rat HIBD model was established using the classic Rice-Vannucci method.Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining.Autophagy-related protein levels of microtubule-associated protein 1 light chain 3(LC3)and Beclin-1 were detected by immunofluorescence staining and Western blot analysis.Phosphorylated phosphoinositide 3-kinase(p-PI3K)and phosphorylated protein kinase B(p-AKT)protein expression levels were measured by immunohistochemistry and Western blot.The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis.Results Twenty-four hours post-modeling,neurons in the sham operation group displayed normal size and orderly arrangement.In contrast,neurons in the HIBD group showed swelling and disorderly arrangement,while those in the melatonin group had relatively normal morphology and more orderly arrangement.Nissl bodies were normal in the sham operation group but distorted in the HIBD group;however,they remained relatively intact in the melatonin group.The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group,but was reduced in the melatonin group compared to the HIBD group(P<0.05).The number of p-PI3K+and p-AKT+cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group(P<0.05).LC3 and Beclin-1 protein expression levels were higher,and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group(P<0.05);however,in the melatonin group,LC3 and Beclin-1 levels decreased,and p-PI3K and p-AKT increased compared to the HIBD group(P<0.05).The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+and p-AKT+cells between the two groups(P<0.05).Conclusions Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD,thereby alleviating HIBD.This mechanism is associated with the PI3K/AKT pathway.

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