1.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
2.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
3.Stage Ⅲ Kümmell's disease treated with injured-vertebra screw placement combined with transpedicular impaction bone grafting:quick restoration of spinal stability
Xuejing ZHENG ; Wei MEI ; Yanyu ZHU ; Xiaoxiao BAO ; Zhenhui ZHANG ; Qingde WANG
Chinese Journal of Tissue Engineering Research 2024;28(18):2865-2870
BACKGROUND:Stage Ⅲ Kümmell's disease is characterized by a high degree of vertebral compression and posterior wall defects.Most of the patients are elderly people with severe osteoporosis and various medical diseases.Clinically,some surgical methods are often at high risk and are controversial. OBJECTIVE:To investigate the clinical efficacy of screw placement combined with transpedicular impaction bone grafting in the treatment of stage Ⅲ Kümmell's disease. METHODS:The clinical data of injured vertebral screw placement combined with transpedicular impaction bone grafting in treatment of stage Ⅲ Kummell's disease from May 2016 to August 2021 were retrospectively analyzed.Visual analog scale score,Oswestry disability index,anterior vertebral heights,kyphotic Cobb angle and American Spinal Injury Association(ASIA)impairment scale were used to evaluate the effects of surgery.The operation time,intraoperative blood loss and complications were recorded.CT scans were used to evaluate the healing of injured vertebrae at the final follow-up visit. RESULTS AND CONCLUSION:(1)A total of 26 patients were included,with 7 males and 19 females,at the age range of 62-81 years[mean(69.7±4.8)years].The follow-up time was 18-60 months[mean(35.1±8.9)months].The average operative duration was 133.5 minutes(100-165 minutes),and the average intraoperative blood loss was 285.3 mL(210-350 mL).(2)Visual analog scale and Oswestry disability index scores 1 week after surgery were significantly lower than those before surgery.(3)At 1 week after surgery,the anterior vertebral height corrections and the Cobb angle were(9.0±0.7)mm and(16.2±1.0)°,respectively.During the follow-up period,the loss of vertebral height and kyphosis correction were(5.1±0.3)mm and(8.0±0.4)°,respectively.(4)14 patients(54%)had ASIA grade D before operation,which recovered to grade E at the last follow-up.CT scan showed that all patients achieved good osseous union.(5)Complications occurred in seven patients(27%),including hypostatic pneumonia in two cases,postoperative superficial wound tissue liquefaction in two cases,and adjacent vertebral compression fractures in three cases.(6)It is concluded that screw placement of the injured vertebra combined with transpedicular impaction bone grafting can rapidly rebuild spinal stability,effectively relieve pain and improve neurological function in the treatment of stage Ⅲ Kümmell's disease.This technique is an effective and relatively minimally invasive surgical option.
4.Promoting Innovative Development of Traditional Chinese Medicine Case Report Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Hongcai SHANG ; Yong ZHU ; Weijun HUANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):190-195
China Clinical Cases Library of Traditional Chinese Medicine is built to promote the establishment of a scientific and technological talent evaluation system oriented on innovative value, ability and contribution in the backgroud of breaking the four only and setting new standards required by the document jointly issued by several national administrations and commissions. In the process of the construction, in order to further consolidate the foundation and ensure the quality and authority of case reports, we need to fully understand the origin and development of Chinese medical cases. Therefore, we clarified the development situation of Chinese medical cases by combing the characteristics of ancient and modern case reports, comparing the differences between Chinese and western medical case reports in terms of content and writing requirements, finally formed the main points of systematic case report norms and quality evaluation system, aiming to fully explore the unique advantages of Chinese medical cases in the fields of discipline development, scientific research innovation, clinical practice and guidance, talent evaluation and training, so as to promote its innovative development in a broader direction.
5.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Pulmonary Nodules
Mingwei YU ; Huairui ZHANG ; Xinghan ZHANG ; Xiao LI ; Rengui WANG ; Zhiqiang LONG ; Zhen WANG ; Bo PANG ; Jianwei HUO ; Wei CHEN ; Yong ZHU ; Baoli LIU ; Yanni LOU ; Ganlin ZHANG ; Jiayun NIAN ; Mei MO ; Xiaoxiao ZHANG ; Guowang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):238-245
In recent years, the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine (TCM) in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine, the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances, TCM theories of etiology and pathogenesis, the role and advantages of TCM in the whole course management of pulmonary nodules, contents and methods of research on pulmonary nodules, and science popularization work, aiming to provide a reference for clinical practice and scientific research. After discussion, the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness, blood stasis, and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules, improving physical constitution, ameliorating multi-system nodular diseases, reducing anxiety and avoiding excessive diagnosis and treatment, and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present, the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed, which needs to be further studied from multiple perspectives such as clinical epidemiology, biology, and evidence-based medicine. The primary task of current research is to find out the advantages, effective prescriptions, and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time, basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized, scientific, and accurate effective diagnosis and treatment.
6.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
7.Application of IgG antibody combination of wild strain and epidemic strain of COVID-19 in identifying epidemic Omicron BA.5 strain infection
Jinjin CHU ; Hua TIAN ; Chuchu LI ; Zhifeng LI ; Chen DONG ; Xiaoxiao KONG ; Jiefu PENG ; Ke XU ; Jianli HU ; Changjun BAO ; Liguo ZHU
Chinese Journal of Preventive Medicine 2024;58(9):1354-1359
Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.
8.Evaluation of clinical effect of position pillows for neuraxial anesthesia
Jing ZHANG ; Jiechu WANG ; Xinyan ZHU ; Xiaoqing ZHANG ; Dong WANG ; Xueyao YU ; Jinjin HUO ; Zhukai CONG ; Yi LIU ; Wei LIU ; Liyuan HAO ; Li FAN ; Xiaoxiao LI
Chinese Journal of Anesthesiology 2024;44(9):1135-1138
Objective:To evaluate the clinical effect of the position pillows for neuraxial anesthesia.Methods:This was a prospective randomized controlled trial. Four hundred and twelve patients regardless of gender, aged ≥18 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, who underwent elective surgery under neuraxial anesthesia at Peking University Third Hospital from February to October 2023, were selected and divided into 2 groups ( n=206 each) using a random number table method: pillow group (P group) and control group (C group). Group C underwent the conventional procedure for neuraxial anesthesia. The patients were placed in a position using the position pillow on the basis of oral education before routine anesthesia in group P. The success rate of puncture at first attempt, puncture time and position placement time were recorded. The adjustment of position, body movement and occurrence of discomfort during the puncture were also recorded. The visual analogue scale score was used to evaluate the level of anxiety before positioning, after positioning and after anesthesia. The visual analogue scale score was used to evaluate the patient′s comfort and the operator′s satisfaction with position after the anesthesia was completed. Results:Compared with group C, the time for positioning was significantly shortened, the anxiety level was decreased after positioning and after anesthesia, the rate of improvement in anxiety was increased, the scores for the patient′s comfort and the operator′s satisfaction with position were increased ( P<0.05), and no significant changes were found in the success rate of puncture at first attempt, puncture time and incidence of body movement during the puncture and incidence of the adjustment of position ( P>0.05). No discomfort was observed in either group during the puncture. Conclusions:This new type of position pillows for the neuraxial anesthesia can not only optimize the effect of position placement, but also improve the patients′ comfort.
9.Application of IgG antibody combination of wild strain and epidemic strain of COVID-19 in identifying epidemic Omicron BA.5 strain infection
Jinjin CHU ; Hua TIAN ; Chuchu LI ; Zhifeng LI ; Chen DONG ; Xiaoxiao KONG ; Jiefu PENG ; Ke XU ; Jianli HU ; Changjun BAO ; Liguo ZHU
Chinese Journal of Preventive Medicine 2024;58(9):1354-1359
Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.
10.Carrier screening for 223 monogenic diseases in Chinese population:a multi-center study in 33 104 individuals
Wei HOU ; Xiaolin FU ; Xiaoxiao XIE ; Chunyan ZHANG ; Jiaxin BIAN ; Xiao MAO ; Juan WEN ; Chunyu LUO ; Hua JIN ; Qian ZHU ; Qingwei QI ; Yeqing QIAN ; Jing YUAN ; Yanyan ZHAO ; Ailan YIN ; Shutie LI ; Yulin JIANG ; Manli ZHANG ; Rui XIAO ; Yanping LU
Journal of Southern Medical University 2024;44(6):1015-1023
Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.