1.Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model
Xia QIU ; Hedong ZHANG ; Zhouqi TANG ; Yuxi FAN ; Wenjia YUAN ; Chen FENG ; Chao CHEN ; Pengcheng CUI ; Yan CUI ; Zhongquan QI ; Tengfang LI ; Yuexing ZHU ; Liming XIE ; Fenghua PENG ; Tuo DENG ; Xin JIANG ; Longkai PENG ; Helong DAI
Chinese Medical Journal 2024;137(12):1453-1464
Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.
2.The impact of DRGs payment on Traditional Chinese Medicine hospitals:Based on difference-in-difference analysis
Hui-Jun GUO ; Jing LIU ; Guang-Yu HU ; Yi-Wei HAO ; Xin-Mei HAO ; Ya-Nan WANG ; Hui-Dong ZHU ; Qiu-Yan LI
Chinese Journal of Health Policy 2024;17(6):47-55
Objective:This study aims to evaluate the impact of Diagnosis-Related-Groups(DRGs)payment on the average total cost,length of stay,service volume,effectiveness,and characteristics of traditional Chinese medicine(TCM)hospitals.Methods:A national medical center specializing in TCM was selected as the research subject.The Difference-in-Difference Model(DID)was utilized to analyze the differences in various indicators between insured patients(intervention group)and uninsured patients(control group)before and after the implementation of the payment reform policy.The reliability and stability of the model were verified through parallel trend tests and placebo tests.Results:The coefficients of DID interaction terms for eleven indicators including average total hospitalization cost,number of cases,length of stay,proportion of medical service revenue,and proportion of herbal medicine revenue were significant(P<0.05).The DID interaction term coefficients for four indicators including herbal medicine usage rate and proportion of non-pharmacological TCM therapy revenue were not significant(P>0.05).Conclusion:DRG payment significantly reduced the per-admission cost,with significant decreases in consumables and medical technology expenses,optimizing cost structure,and a slight decrease in the proportion of herbal medicine costs.It is necessary to further expand the sample size,track policy impacts,and comprehensively evaluate the effects of DRG payment on TCM hospitals in China.
3.Different diagnostic methods for necrospermia and correlation between the severity of sperm necrosis and sperm DNA fragmentation index
Lang FAN ; Guo-Qiong ZHANG ; Yu-Qiu TAN ; Wen-Xing ZHU ; Xi-Yan WU
National Journal of Andrology 2024;30(10):872-877
Objective:To assess the value eosin-nigrosine(E-N)staining and hypo-osmotic swelling test(HOST)in the diag-nosis of necrospermia and investigate the correlation of the degree of sperm necrosis with sperm DNA fragmentation index(DFI)and high DNA stainability(HDS).Methods:Using computer-assisted sperm analysis(CASA),we examined the sperm motility of 7 333 males seeking medical care in Maternal and Child Health Hospital of Hunan Province from May 2023 to July 2024,detected the sperm viability of those with asthenozoospermia by E-N staining and HOST,and measured the sperm DFI and HDS of those with necro-spermia by sperm chromatin structure assay(SCSA).Based on sperm progressive motility(PR%),we divided the asthenozoospermia patients into three groups(PR%20%-<30%,PR%10%-<20%and PR%<10%),assessed the value of E-N staining and HOST in the diagnosis of necrospermia,and analyzed the correlation of the severity of sperm necrosis with sperm DFI and HDS.Results:Asthenozoospermia was diagnosed in 1 374(18.74%)of the 7 333 males.The incidence rates of necrospermia revealed by E-N staining in the mild,moderate and severe asthenozoospermia groups were 0.55%(5/913),3.80%(12/316)and 35.86%(52/145),respectively,with a total incidence of 0.94%(69/7333),while those detected by HOST were 0.99%(9/913),6.96%(22/316)and 46.21%(67/145),respectively,with a total incidence of 1.34%(98/7333).There were no statistically significant differences in the results of diagnosis between the two methods(x2=0.97,P>0.05).Both E-N staining and HOST showed that sperm DFI in the necrospermia males was negatively correlated with sperm viability(r=-0.366,r=-0.333,P<0.05),and so was sperm HDS,though with no statistically significant difference(P>0.05).Conclusion:For males with PR%<30%,sperm viability test should be conducted,with E-N staining as the choice of priority for the diagnosis of necrospermia.Sperm necrosis and sperm nuclear chromatin damage may be interactive risk factors.
4.Effectiveness of three electronic fetal monitoring systems in identifying neonatal acidosis during labor
Lili QIU ; Huilian HU ; Ling YANG ; Ning GU ; Zhenhua ZHU ; Jing FANG ; Yan ZHOU ; Yimin DAI
Chinese Journal of Perinatal Medicine 2024;27(5):362-370
Objective:To analyze the effectiveness and interobserver agreement of the Parer five-tier, the National Institute of Child Health and Human Development (NICHD) three-tier, and the International Federation of Gynecology and Obstetrics (FIGO) three-tier electronic fetal monitoring (EFM) systems in identification of neonatal acidosis during labor.Methods:This retrospective study was conducted on full-term singleton cephalic deliveries with neonatal acidosis (umbilical artery blood gas pH≤7.1) and normal newborns (umbilical artery blood gas pH≥7.2) in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January to December 2020. EFM tracings during the last 30-60 min before delivery were collected. Four obstetricians independently described the features of randomly sorted and coded EFM tracings. Another obstetrician categorized these tracings using the NICHD three-tier, FIGO three-tier, and Parer five-tier evaluation systems based on the features. All researchers were masked to the clinical characteristics and maternal and neonatal outcomes. The sensitivity and specificity for identifying neonatal acidosis, as well as the interobserver agreement, were analyzed for all three systems. Independent sample t-test, Chi-square (or Fisher's exact test) and Mann-Whitney U tests were used for statistical analysis. Inter-group comparisons of sensitivity and specificity between the three evaluation systems were assessed using McNemar's test. The Kappa statistic was used to analyze interobserver agreement. Results:This study included a total of 3 558 cases. After propensity score matching, there were 44 cases of neonatal acidosis and 78 control cases. There were no significant differences in parity, gestational weeks, modes of delivery, placental abruption, or analgesia rates between the two groups. The rates of instrumental vaginal delivery and neonatal intensive care unit (NICU) admission in the acidosis group were significantly higher than those in the control group [15.8% (7/44) vs. 2.6% (2/78), χ2=8.45, P=0.003; 31.8% (14/44) vs. 12.8% (10/78), χ2=8.45, P=0.004], while the umbilical artery blood pH and mean base excess were lower in the acidosis group than in the control group [7.04±0.07 vs. 7.30±0.05, t=4.98; (-12.40±3.32) vs. (-5.64±1.95) mmol/L, t=13.61; both P<0.001]. (2) Using the NICHD three-tier system, 95.5% (42/44) of the acidosis cases and 89.7% (70/78) of the control cases were classified as having category Ⅱ EFM tracings, indicating potential fetal acid-base imbalance; category Ⅲ EFM tracings were only observed in 4.5% (2/44) of the cases in the acidosis group. With the FIGO three-tier system, 81.8% (36/44) of the acidosis cases were categorized as having "pathological" tracings, and with the Parer five-tier system, 86.4% (38/44) of the acidosis cases were correctly classified into the "orange or red" risk zones that indicated acid-base imbalance. Among the control cases, there were 28.2% (22/78) with EFM tracings of "normal patterns" categorized by the FIGO three-tier system, and 41.0% (32/78) classified into the "green or blue" risk zones by the Parer five-tier system, which indicated good fetal conditions. None of the acidosis cases were misdiagnosed as being normal by the Parer five-tier system. (3) Compared with the NICHD three-tier system, both the FIGO three-tier and the Parer five-tier systems showed increased diagnostic sensitivity [4.5% (1.2%- 14.5%) vs. 81.8% (66.8%-89.4%) and 86.4% (71.8%-92.4%)], but decreased specificity [100.0% (95.3%- 100.0%) vs. 87.2% (78.0%-92.9%) and 84.6% (75.0%-91.0%)]. There was no statistically significant difference in the sensitivity or specificity between the FIGO three-tier and Parer five-tier systems for identifying neonatal acidosis ( P=0.727 and 0.791). (4) When reading the tracings of control cases, the total agreement rate for the NICHD three-tier system by different observers was as high as 94.2%, while the total agreement rates for the FIGO three-tier and Parer five-tier systems were 69.7% and 67.7%, respectively. In the interpretation of EFHR tracings for acidosis cases, the interobserver agreement for the Parer five-tier system was excellent [Kappa (95% CI): 0.87 (0.79-0.95)], while both the NICHD three-tier and FIGO three-tier systems showed good agreement [Kappa (95% CI): 0.77 (0.66-0.88) and 0.72 (0.60-0.84)]. Conclusions:The Parer five-tier and the FIGO three-tier systems have higher sensitivity in identifying neonatal acidosis than the NICHD three-tier system, and the Parer five-tier system achieves a higher negative predictive value and a greater agreement in the interpretation of pathological EFM patterns.
5.Functional near infrared imaging of college students on speech fluency tasks in traumatized
ZHENG Minxiao, ZHU Dongmei, WEI Qiang, XIANG Nian, QIU Min, XIAO Qiang, LI Xiaonan, ZHANG Yan
Chinese Journal of School Health 2024;45(3):375-378
Objective:
The study aims to explore the neural mechanism of cognitive differences in college students with posttraumatic stress disorder under verbal fluency task based on functional near infrared spectroscopy (fNIRS), so as to provide neuroimaging support for the evaluation, diagnosis and treatment of posttraumatic stress disorder(PTSD).
Methods:
Posttaumatic Stress Disorder Checklist Combat(PCL-C) was used to screen the subjects, including 21 students in PTSD group (PCL-C≥38) and 30 students in control group from September to Novenber in 2020. A 53 channel near infrared spectroscopy device was used to collect cerebral blood oxygen signals under the verbal fluency task, and correlation analysis, Mann Whitney U test and independent sample t test were performed on the results.
Results:
The difference in the total average score of PCL-C Scale between PTSD group and the control group(46.38±6.96,25.57±6.09) was statistically significant ( t=11.33, P <0.05). Correlation analysis showed that Avg-HbO in left dorsolateral prefrontal lobe was negatively correlated with PCL-C Score ( r=-0.37, P <0.05). Mann Whitney U test showed that in the left dorsolateral prefrontal lobe (Ch6), the Avg-HbO change in PTSD group [0.19(-0.09, 0.86)mmol/(L〖KG*7〗·mm)] was significantly lower than the control group [0.79( 0.37 , 1.47)mmol/(L ·mm)] ( Z=2.16, P <0.05), which was statistically significant.
Conclusions
The degree of PTSD was negatively correlated with the index of oxygenated hemoglobin in the left dorsolateral prefrontal lobe, and the oxygenated hemoglobin content in the PTSD group was lower than that in the normal group. In the future, fNIRS may be used to collect blood oxygen signals from the left dorsolateral prefrontal lobe in cognitive tasks to provide imaging evidence for the identification of PTSD.
6.Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway.
Jun-Peng YAO ; Xiu-Mei FENG ; Lu WANG ; Yan-Qiu LI ; Zi-Yue ZHU ; Xiang-Yun YAN ; Yu-Qing YANG ; Ying LI ; Wei ZHANG
Chinese journal of integrative medicine 2024;30(3):251-259
OBJECTIVE:
To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway.
METHODS:
Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR.
RESULTS:
The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01).
CONCLUSIONS
EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats
;
Male
;
Animals
;
Rats, Sprague-Dawley
;
Electroacupuncture
;
Phosphatidylinositol 3-Kinase/metabolism*
;
Facial Nerve Injuries/therapy*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Beclin-1
;
Glial Cell Line-Derived Neurotrophic Factor
;
Signal Transduction
;
TOR Serine-Threonine Kinases/metabolism*
;
Autophagy
;
Mammals/metabolism*
7.Exploration on Acupuncture and Moxibustion Treatment Ideas for Gynecological Reproductive Diseases Based on the"Heart-kidney-Chong Ren-uterus"Reproductive Axis
Mohao ZHU ; Ling QIU ; Wenhua HAN ; Tianya YAN ; Yixuan XING ; Shi TANG ; Weiai LIU ; Zhaoling YOU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):167-172
This article mainly elaborated the acupuncture and moxibustion treatment scheme of"eighteen needles for reproduction"based on Professor You Zhaoling's reproductive axis theory of"heart-kidney-Chong Ren-uterus".The"eighteen needles for reproduction"aims to regulate the disordered reproductive axis in gynecological reproductive diseases.It selects the acupoints on the main viscera and meridians of the reproductive axis as the main acupoints,and the acupoints regulating the qi and blood of the related viscera as the matching acupoints.Through specific manipulation,it can regulate the qi and blood,dredge the meridians,and treat the viscera,so as to nourish the essence and help pregnancy,and provide ideas and reference for the treatment of gynecological reproductive diseases with acupuncture and moxibustion.
8.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
9.Study on the Knowledge-Attitude-Practice questionnaire for patients receiving oral anticoagulant therapy based on the Delphi method
Xiaomei LEI ; Na WANG ; Qiao LING ; Xinting ZHU ; Sha QIU ; Daiyi LI ; Yan QIAN
China Pharmacy 2024;35(10):1260-1265
OBJECTIVE To develop a questionnaire of the Knowledge-Attitude-Practice (KAP) for patients receiving oral anticoagulant therapy. METHODS Under the guidance of the theory of KAP, literature analysis and interview method were used to design the initial KAP questionnaire for patients treated with oral anticoagulants. Delphi method was adopted to consult the initial questionnaire and modify the questionnaire based on expert suggestions to form the final questionnaire. RESULTS Two rounds of consultation were conducted with 18 experts, and 18 questionnaires were sent out and recovered in each round, so the positive coefficient of experts was 100%. The expert authority coefficient was 0.94. The average importance scores for all dimensions, factors, and items of the questionnaire in both rounds were ≥4 points. The coefficient of variation was ≤0.25. The Kendall’s concordance coefficient for the overall questionnaire and the three dimensions of knowledge, attitude, and practice ranged from 0.09 to 0.34 (all P<0.05). Following the first round of expert consultation, four items were modified, two items were deleted, and five items were added; after the second round of expert consultation, ten items were modified. The final version of the questionnaire included three dimensions (knowledge, attitudes, and practice), 17 questionnaire factors, and 40 items. CONCLUSIONS The questionnaire has high reliability and scientific validity with relatively concentrated expert opinions. It is suitable for assessing the knowledge, attitudes, and practice status of patients receiving oral anticoagulant therapy.
10.Clinical trial of menatetrenone combined with PKP in the treatment of patients with osteoporotic vertebral compression fracture
Yan ZHU ; Lei-Yu QIU ; Xiao ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(10):1409-1413
Objective To observe the effect and safety of menatetrenone combined with percutaneous kyphoplasty(PKP)in the treatment of osteoporotic vertebral compression fracture(OVCF).Methods Patients with OVCF were divided into treatment group and control group by random number table method.The control group was treated with PKP and conventional anti-osteoporosis treatment,and the treatment group was treated with menatetrenone 15 mg,tid,on the basis of control group.The two groups were compared on the changes in T value of bone mineral density,Oswestry disability index(ODI)scores,visual analogue scale(VAS)and bone metabolism indicators[osteocalcin(OC),alkaline phosphatase(ALP),C-telopeptide of type Ⅰ collagen(CTX-Ⅰ)and 25-hydroxyvitamin D(25(OH)D)].The incidence rates of refracture and adverse reactions were recorded.Results There were 40 cases in treatment group and 40 cases in control group.After treatment,T values of bone mineral density of lumbar spine(L2-4)in treatment group and control group were-1.79±0.24 and-2.16±0.28;T values of bone mineral density of femoral neck were-1.44±0.16 and-2.01±0.22;T values of bone mineral density of femoral great trochanter were-1.76±0.18 and-1.97±0.23,all with significant difference(all P<0.05).Three months after operation,ODI scores in treatment group and control group were 34.12±3.56 and 37.67±3.89;six months after operation,ODI scores were 17.85±1.84 and 26.75±2.78;three months after operation,VAS were 2.61±0.28 and 2.84±0.31;six months after operation,VAS were 0.85±0.11 and 1.23±0.16,all with significant difference(all P<0.05).After treatment,OC levels in treatment group and control group were(9.08±0.95)and(7.64±0.79)μg·L-1;ALP levels were(86.27±8.79)and(91.33±9.25)U·L-1;CTX-Ⅰ levels were(0.21±0.04)and(0.25±0.03)ng·mL-1;the above indexes were significantly different between control group and treatment group(all P<0.05).The incidence of refracture in treatment group and control group were 10.00%and 2.50%,and the incidence of adverse drug reactions were 10.00%and 17.50%,without statistically significant difference between the two groups(all P>0.05).Conclusion Menatetrenone combined with PKP can significantly increase bone mineral density of patients with OVCF,improve bone metabolism indicators and reduce lumbar dysfunction and pain,without increasing the risks of refracture and adverse drug reactions.


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