Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Purpose: We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. Results: 2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. Conclusion EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective: To investigate the predictive factors for bronchitis obliterans in refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods: A restrospective case summary was conducted 230 patients with RMPP admitted to the Department of No.2 Respiratory Medicine of Beijing Children's Hospital, Capital Medical University from January 2013 to June 2017 were recruited. Clinical data, laboratory results, imaging results and follow-up data were collected. Based on bronchoscopy and imaging findings 1 year after discharge, all patients were divided into two groups: one group had sequelae of bronchitis obliterans (sequelae group) and the other group had not bronchitis obliterans (control group), independent sample t-test and nonparametric test were used to compare the differences in clinical features between the two groups. Receiver operating characteristic (ROC) curve to explore the predictive value of Bronchitis Obliterans in RMPP. Results: Among 230 RMPP children, there were 115 males and 115 females, 95 cases had sequelae group, the age of disease onset was (7.1±2.8) years;135 cases had control group, the age of disease onset was (6.8±2.7) years. The duration of fever, C-reative protein (CRP) and lactate dehydrogenase (LDH) levels, the proportion of ≥2/3 lobe consolidation, pleural effusion and the proportion of airway mucus plug and mucosal necrosis were longer or higher in the sequelae group than those in the control group ((17±9) vs. (12±3) d, (193±59) vs. (98±42) mg/L,730 (660, 814) vs. 486 (452, 522) U/L, 89 cases (93.7%) vs. 73 cases (54.1%), 73 cases (76.8%) vs.59 cases (43.7%), 81 cases (85.3%) vs. 20 cases (14.8%), 67 cases (70.5%) vs. 9 cases (6.7%), t=5.76, 13.35, Z=-6.41, χ²=14.64, 25.04, 22.85, 102.78, all P<0.001). Multivariate Logistic regression analysis showed that the duration of fever ≥10 days (OR=1.200, 95%CI 1.014-1.419), CRP levels increased (OR=1.033, 95%CI 1.022-1.044) and LDH levels increased (OR=1.001, 95%CI 1.000-1.003) were the risk factors for sequelae of bronchitis obliterans in RMPP. ROC curve analysis showed that CRP 137 mg/L had a sensitivity of 82.1% and a specificity of 80.1%; LDH 471 U/L had a sensitivity of 62.7% and a specificity of 60.3% for predicting the development of bronchitis obliterans. Conclusions: The long duration of fever (≥10 d), CRP increase (≥137 mg/L) may be used to predict the occurrence of sequelae of bronchitis obliterans in RMPP. It is helpful for early recognition of risk children.
Child ; Male ; Female ; Humans ; Child, Preschool ; Mycoplasma pneumoniae ; Retrospective Studies ; Pneumonia, Mycoplasma/complications* ; Disease Progression ; L-Lactate Dehydrogenase ; Fever

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.
Mice ; Male ; Animals ; NF-kappa B/metabolism* ; Interleukin-8 ; Interleukin-10 ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; I-kappa B Kinase ; Spleen ; Irbesartan ; Uridine Triphosphate ; Yang Deficiency/drug therapy* ; Kidney/pathology*

Objective: The aim of this study was to summarize the clinical and imaging characteristics of post-primary tuberculosis in children, so as to improve the early identification and diagnosis of post-primary tuberculosis. Methods: This was a retrospective study which enrolled children who were admitted to the Department No.2 of Respiratory Medicine, Beijing Children's Hospital Affiliated to Capital Medical University between January 2015 to December 2020 and with a diagnosis of post-primary tuberculosis. Results: A total of 30 patients were enrolled, including 10 males and 20 females. The age on admission were 13.0 (12.0, 13.3) years. Their common symptoms were cough and fever, there were 26 cases (87%) with cough and 23 cases (77%) with fever, but only 4 cases (13%) had other toxic symptoms (night sweat, weakness or weight loss) of tuberculosis other than fever. Blood examination showed that the white blood cell count was (10±3)×10⁹/L, accompanied by elevated proportion of neutrophils (0.69±0.11) and increased level of C-reactive protein (31 (15,81) mg/L). The common radiographic findings of CT were nodular or mass shadow with cavitation (19 cases (63%)), consolidation (13 cases (43%)), bronchogenic spread (12 cases (40%)), hilar or mediastinal lymphadenopathy (5 cases (17%)) in this cohort. The affected locations included the right upper lobe (21 cases (70%)), the left lower lobe (17 cases (57%)) and the right lower lobe (15 cases (50%)). Acid-fast bacillus smears and mycobacterial cultures were attempted for all cases, resulting in 33% (10/30) with smear positivity and 50% (15/30) with culture positivity. Conclusions: Post-primary tuberculosis in children has no specific clinical manifestations. Imaging of chest CT is mainly manifested as nodular shadow with cavitation, consolidation or bronchogenic spread. Accurate identification of post-primary tuberculosis is crucial for preventing the spread and early treatment of tuberculosis.
Child ; Cough/etiology* ; Female ; Humans ; Lung ; Lung Diseases ; Male ; Retrospective Studies ; Tuberculosis/diagnosis*

OBJECTIVE: According to 73 patients with middle clavicle fracture treated conservatively, a new classification of middle clavicle fracture was proposed, and the clinical effect of plastic splint in the treatment of middle clavicle fracture was observed. METHODS: Total 73 patients with middle clavicle fracture treated with plastic splint from September 2018 to August 2020 were analyzed retrospectively. All the patients were divided into 4 types according to the degree of fracture displacement. There were 16 cases of typeⅠ, including 7 males and 9 females, ranging in age from 18 to 37 years old, with a mean of (28.6±7.8) years old;12 cases of mild disease, 3 cases of moderate disease and 1 case of severe disease. There were 16 cases of type Ⅱ, including 6 males and 10 females, ranging in age from 25 to 49 years old, with a mean of (37.3±9.4) years old;5 cases of mild disease, 8 cases of moderate disease and 3 cases of severe disease. There were 7 cases of type Ⅲ, including 4 males and 3 females, ranging in age from 33 to 57 years old;2 cases of mild disease, 3 cases of moderate disease and 2 cases of severe disease. There were 34 cases of type Ⅳ, including 16 males and 18 females, ranging in age from 48 to 82 years old, with a mean of(66.4±14.9) years old;7 cases of mild disease, 17 cases of moderate disease and 10 cases of severe disease. All patients received plastic splint external fixation for 4 weeks. Visual analgue scale (VAS) and Constant-Murley shoulder scores before treatment and 1, 3 and 9 months after treatment were observed and recorded to evaluate the change of pain degree and shoulder function recovery before and after treatment. The patients' satisfaction with the appearance after treatment was recorded at the latest follow-up. The X-ray findings at the latest follow-up were used to judge whether the patient had fracture nonunion. And according to the fracture healing time and imaging findings, the excellent and good rate of clinical curative effect in patients with different types was obtained. RESULTS: All patients were followed up, and the duration ranged from 9 to 11 months, with a mean of (9.8±0.7) months. The VAS scores of typeⅠ, typeⅡand type Ⅳ before treatment were 2.88±0.83, 3.67±0.80 and 6.92±1.71 respectively, which were decreased to 0.54±0.19, 0.77±0.25 and 1.18±0.17 respectively after 9 months of treatment. The Constant-Murley shoulder scores of typeⅠ, typeⅡand type Ⅳ were 65.81±2.09, 63.50±2.22 and 47.93±2.91 respectively before treatment, and increased to 88.56±2.11, 85.12±2.23 and 71.25±2.16 respectively after 9 months of treatment. Five patients were not satisfied with the appearance after treatment;6 patients had no obvious continuous callus passing through after 9 months of treatment, which was fracture nonunion. CONCLUSION The classification of middle clavicle fracture is more appropriate to the clinic, which has a certain clinical guiding significance for the selection of treatment methods and prognosis of middle clavicle fracture. Plastic splint is effective in the treatment of middle clavicle fracture without obvious displacement and overlapping displacement, and the incidence of complications is low. It can be popularized in clinic.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Plates ; Clavicle/diagnostic imaging* ; Female ; Fracture Fixation, Internal/methods* ; Humans ; Male ; Middle Aged ; Plastics ; Retrospective Studies ; Splints ; Young Adult

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy