AIM To investigate the mechanism of triterpenoids quillaic acid and gypsogenin-3-O-glucuronide from Psammosilene tunicoides on tunicamycin-induced rheumatoid arthritis fibroblasts-like synoviocytes(RA-FLS)via the endoplasmic reticulum pathway.METHODS The research objects of tunicamycin-induced RA-FLS intervened with quillaic acid and gypsogenin-3-O-glucuronide had their cell proliferation activity detected;their level of tumor nerosis factor-α(TNF-α)detected by ELISA;their apoptosis detected by flow cytometry;their cell migration ability detected by Transwell experiment;their expressions of transcription activator 6(ATF-6),glucose regulatory protein 78(GRP78),C/EBP homologous protein(CHOP),cysteine protease protein-12(caspase-12)and anti-apoptosis Bcl-2 protein detected by Western blot;and their mRNA expressions of ATF-6,GRP78 and CHOP detected by RT-qPCR.RESULTS Compared with the model group,each group intervened with quillaic acid or gypsogenin-3-O-glucuronide displayed decreased levels of TNF-α(P＜0.01);weakened cell proliferation and migration ability(P＜0.01);increased apoptosis rate(P＜0.01);decreased protein expressions of ATF-6 and Bcl-2(P＜0.05,P＜0.01);and increased protein expressions of CHOP and caspase-12(P＜0.05,P＜0.01).In addition,decreased GRP78 protein expression in the low and medium dose groups(P＜0.05,P＜0.01);decreased mRNA expression of ATF-6,GRP78(P＜0.01)and increased CHOP mRNA expression(P＜0.01)in the medium dose groups of quillaic acid and gypsogenin-3-O-glucuronide were observed as well.CONCLUSION Quillaic acid and gypsogenin-3-O-glucuronide may play a protective role in rheumatoid arthritis by inhibiting the proliferation and migration of RA-FLS,inducing apoptosis and reducing the secretion of related inflammatory factors via endoplasmic reticulum signal pathway.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

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.

Objective To investigate the distribution of the traditional Chinese medicine(TCM)constitution types in the patients with nonspecific low back pain(NLBP)and to explore the correlation of the thickness of ligamentum flavum with the age,body mass index(BMI),gender,the presence of diabetes mellitus,and the grading of hypertension.Methods Sixty patients with NLBP admitted to Guangdong Second Traditional Chinese Medicine Hospital from January 2023 to June 2023 were selected as the study subjects.The TCM constitution types of the patients were identified,the thickness of the ligamentum flavum at lumbar vertebrae 4/5 segment(L4/5)disc level was measured by computerized tomography(CT)scanning,and the patients'age,genders,TCM constitution types,BMI,the presence or absence of diabetes mellitus,and hypertension grading were recorded.Correlation analysis and linear regression analysis were used for the exploration of the relevant influencing factors for the thickness of the ligamentum flavum of patients with NLBP.Results(1)The average thickness of ligamentum flavum in the 60 patients with NLBP was(2.60±0.72)mm.(2)The TCM constitutions of NLBP patients were classified into four types,of which blood stasis constitution was the most common,accounting for 21 cases(35.0%),followed by 19 cases(31.7%)of damp-heat constitution,12 cases(20.0%)of phlegm-damp constitution,and 8 cases(13.3%)of qi deficiency constitution.(3)The results of correlation analysis showed that BMI,gender,TCM constitution type and the presence or absence of diabetes mellitus had no influence on the thickness of ligamentum flavum in NLBP patients(P＞0.05),while the age and hypertension grading had an influence on the thickness of ligamentum flavum(P＜0.01).(4)The results of linear regression analysis showed that the age had an influence on the thickness of the ligamentum flavum(b = 0.034,t = 6.282,P＜0.01),while the influence of the hypertension grading had no influence on the thickness of the ligamentum flavum(P＞0.05).Conclusion The TCM constitution type of NLBP patients is predominated by blood stasis constitution,the thickness of ligamentum flavum is significantly affected by the age,and hypertension may be a potential factor affecting the thickness of ligamentum flavum.

Objective To observe the clinical efficacy of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula for the treatment of lumbar spinal stenosis(LSS)with qi deficiency and blood stasis syndrome.Methods Sixty patients with LSS of qi deficiency and blood stasis type were randomly divided into trial group and control group,with 30 cases in each group.The trial group was treated with"triple-posture positive bone-setting"chiropractic manipulation(a chiropractic manipulation performed under the positive cooperation of the patients at three postures)combined with Tongluo Huoxue Formula,while the control group was treated with"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medicine.The course of treatment for the two groups covered 4 weeks.Before and after treatment,the patients of the two groups were observed in the changes of pain visual analogue scale(VAS)score,Japanese Orthopedic Association(JOA)score of lumbar function,Oswestry Disability Index(ODI)score,straight-leg raising test results and serum interleukin 6(IL-6)and C-reactive protein(CRP)levels.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the trial group was 96.67％(29/30)and that of the control group was 63.33％(19/30).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the lumbar function indicators of pain VAS scores and ODI scores in the trial group were significantly lower(P＜0.05),and the JOA scores were significantly higher than those before treatment(P＜0.05),while in the control group,only the ODI scores were significantly lower than those before treatment(P＜0.05).The intergroup comparison showed that the decrease of VAS and ODI scores and the increase of JOA scores in the trial group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(3)After treatment,the Laseque s sign of the trial group was significantly improved compared with that before treatment(P＜0.05),while no significant improvement was presented in the control group(P＞0.05).The intergroup comparison showed that the improvement of Laseque's sign in the trial group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of serum inflammatory factors of IL-6 and CRP in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-6 level in the trial group was significantly superior to that in the control group(P＜0.05),but CRP level in the two groups after treatment did not differ from that before treatment,no statistically significant difference was shown between the two groups after treatment,either(P＞0.05).(5)The incidence of adverse reactions in the trial group was 6.67％(2/30)and that in the control group was 13.33％(4/30),and the intergroup comparison(by Fisher's exact test)showed that there was no significant difference between the two groups(P＞0.05).Conclusion The therapeutic effect of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula exert certain effect for the treatment of LSS patients with qi deficiency and blood stasis syndrome,and it has more obvious advantages in improving the lumbar function,promoting the rehabilitation of the patients,and lowering the level of serum inflammatory factors than"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medication.

Objective: To investigate the long-term outcomes of patients with unilateral vocal fold paralysis resulting in dysphonia treated with lateral vocal fold autologous fat injection. To analyze the factors that may affect the long-term efficacy of the procedure. Methods: From July 2003 to June 2020, 163 patients (86 males and 77 females), aged 9-73 years (mean (34.50±12.94) years) with unilateral vocal fold paralysis resulting in dysphonia underwent transoral laryngoscopic injection of autologous fat into the lateral vocal folds. Subjective auditory perception assessment (GRBAS scale), objective acoustic assessment, voice handicap index (VHI) evaluation and stroboscopic laryngoscopy were compared before and after the surgery. Patients were followed up for 1 to 18 years, with median follow-up time of 6 years. SPSS 22.0 software was used for statistical analysis. Results: Of 163 patients, 17 patients (10.4%) had mild hoarseness (G1) and 146 patients (89.6%) had moderate to severe hoarseness (G2-3). Stroboscopic laryngoscopy revealed an arch-shaped vocal fold on the affected side, fixed in the paramedian position or abduction position, with obvious glottic closure fissure. Postoperatively, voice recovered to normal (G0) in 139 patients (85.3%), mild hoarseness (G1) in 18 patients (11.0%) and moderate hoarseness (G2) in 6 patients (3.7%). Of these, 131 patients (80.4%) showed significant improvement in hoarseness, 29 patients (17.8%) showed mild improvement and 3 patients (1.8%) showed no significant improvement in hoarseness. Objective acoustic parameters of Jitter, Shimmer, NHR and MPT improved significantly, as did VHI scores. Stroboscopic laryngoscopy showed medialization of the affected vocal folds, improved vocal fold closure and normal or nearly normal vocal fold mucosal waves. With a fat injection volume of 3.0-4.5 ml, the patient's subjective auditory perception scores of G, R, B and A improved more significantly within 3 months after surgery, and both VHI and MPT were significantly better since 1 year after surgery. With bilateral vocal fold injection, the B and A scores improved significantly from 1 month postoperatively compared to unilateral injections(unilateral vs. bilateral injection 1 month post-operation, t_{B scores}=1.42,t_{A scores}=1.51,P<0.05). Conclusions: The long-term efficacy of autologous fat injection in the paraglottic space for the treatment of unilateral vocal fold paralysis was stable. The efficacy of the surgery was related to the amount of fat injected, unilateral or bilateral of the injection.
Male ; Female ; Humans ; Vocal Cords/surgery* ; Dysphonia/surgery* ; Hoarseness ; Treatment Outcome ; Vocal Cord Paralysis/surgery*

Glial cells, consisting of astrocytes, oligodendrocyte lineage cells, and microglia, account for >50% of the total number of cells in the mammalian brain. They play key roles in the modulation of various brain activities under physiological and pathological conditions. Although the typical morphological features and characteristic functions of these cells are well described, the organization of interconnections of the different glial cell populations and their impact on the healthy and diseased brain is not completely understood. Understanding these processes remains a profound challenge. Accumulating evidence suggests that glial cells can form highly complex interconnections with each other. The astroglial network has been well described. Oligodendrocytes and microglia may also contribute to the formation of glial networks under various circumstances. In this review, we discuss the structure and function of glial networks and their pathological relevance to central nervous system diseases. We also highlight opportunities for future research on the glial connectome.
Animals ; Neuroglia/physiology* ; Neurons/physiology* ; Astrocytes ; Microglia/physiology* ; Oligodendroglia ; Mammals

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal