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*

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.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Aim To design the pyrimidoindole deriva-tive N-butyl-9H-pyrimido[4,5-b]indole-2-carboxamide(BFPI)and synthesize it to investigate whether it in-hibits macrophage pyroptosis and foaming effects through the NLRP3/Caspase-1 pathway.Methods BFPI was synthesized using 2,4,6-triethoxycarbonyl-l,3,5-triazine and 2-aminoindole as starting materials and structurally characterized by 1H NMR,13C NMR,and ESI-MS.The in vitro cultured mouse monocyte macro-phage cell line RAW264.7 was divided into blank,model(PA)and therapeutic(BFPI)groups,and the cells in each group were treated with the corresponding culture medium for 24 h.The proliferative viability was detected by MTT assay,and the formation of intracel-lular lipid droplets was detected by oil red O staining,and NLRP3 was detected by Western-blot and RT-qPCR,caspase-1 and MCP-1 mRNA and protein ex-pression levels by Western blot and RT-qPCR.Results Compared with the blank group,the proliferation vi-ability of cells in the model group significantly de-creased and the formation of lipid droplets significantly increased;compared with the model group,the prolif-eration viability of cells in the treatment group signifi-cantly increased and the formation of lipid droplets sig-nificantly decreased,and the differences were statisti-cally significant(P＜0.01);compared with the blank group,the cellular NLRP3,caspase-1 and MCP-1 mR-NA and protein expression levels of cells in the model group significantly increased;compared with the model group,the expression levels of the above indexes of the cells in the treatment group significantly decreased,and the difference was statistically significant(P＜0.01).Conclusions BFPI contributes to delaying macrophage-derived foam cell formation during athero-genesis by inhibiting macrophage NLRP3,caspase-1,and MCP-1 expression and thereby promoting their pro-liferation and inhibiting lipid phagocytosis.

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.
Male ; Mice ; Animals ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Glycogen ; Yang Deficiency/drug therapy* ; Yin Deficiency/drug therapy* ; Kidney ; Body Weight

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 compare the efficacy and muscle injury imaging between oblique lateral lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of single-segment degenerative lumbar spinal stenosis. METHODS: The clinical data of 60 patients with single-segment degenerative lumbar spinal stenosis who underwent surgical treatment from January 2018 to October 2019 was retrospectively analyzed. The patients were divided into OLIF groups and TLIF group according to different surgical methods. The 30 patients in the OLIF group were treated with OLIF plus posterior intermuscular screw rod internal fixation. There were 13 males and 17 females, aged from 52 to 74 years old with an average of (62.6±8.3) years old. And 30 patients in the TLIF group were treated with TLIF via the left approach. There were 14 males and 16 females, aged from 50 to 81 years old with an average of (61.7±10.4) years old. General data including operative time, intraoperative blood loss, postoperative drainage volume, and complications were recorded for both groups. Radiologic data including disc height (DH), the left psoas major muscle, multifidus muscle, longissimus muscle area, T2-weighted image hyperintensity changes and interbody fusion or nonfusion were observed. Laboratory parameters including creatine kinase (CK) values on postoperative 1st and 5th days were analyzed. Visual analogue scale(VAS) and Oswestry disability index(ODI) were used to assess clinical efficacy. RESULTS: There was no significant difference in the operative time between two groups(P>0.05). The OLIF group had significantly less intraoperative blood loss and postoperative drainage volume compared to the TLIF group(P<0.01). The OLIF group also had DH better recovery compared to the TLIF group (P<0.05). There were no significant differences in left psoas major muscle area and the hyperintensity degree before and after the operation in the OLIF group (P>0.05). Postoperativly, the area of the left multifidus muscle and longissimus muscle, as well as the mean of the left multifidus muscle and longissimus muscle in the OLIF group, were lower than those in the TLIF group (P<0.05) .On the 1st day and the 5th day after operation, CK level in the OLIF group was lower than that in the TLIF group(P<0.05). On the 3rd day after operation, the VAS of low back pain and leg pain in the OLIF group were lower than those in the TLIF group (P<0.05). There were no significant differences in the ODI of postoperative 12 months, low back and leg pain VAS at 3, 6, 12 months between the two groups(P>0.05). In the OLIF group, 1 case of left lower extremity skin temperature increased after the operation, and the sympathetic chain was considered to be injured during the operation, and 2 cases of left thigh anterior numbness occurred, which was considered to be related to psoas major muscle stretch, resulting in a complication rate of 10% (3/30). In the TLIF group, one patient had limited ankle dorsiflexion, which was related to nerve root traction, two patients had cerebrospinal fluid leakage, and the dural sac was torn during the operation, and one patient had incision fat liquefaction, which was related to paraspinal muscle dissection injury, resulting in a complication rate of 13% (4/30). All patients achieved interbody fusion without cage collapse during the 6- month follow-up. CONCLUSION Both OLIF and TLIF are effective in the treatment of single-segment degenerative lumbar spinal stenosis. However, OLIF surgery has obviously advantages, including less intraoperative blood loss, less postoperative pain, and good recovery of intervertebral space height. From the changes in laboratory indexes of CK and the comparison of the left psoas major muscle, multifidus muscle, longissimus muscle area, and high signal intensity of T2 image on imaging, it can be seen that the degree of muscle damage and interference of OLIF surgery is lower than that of TLIF.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Spinal Stenosis/surgery* ; Blood Loss, Surgical ; Lumbar Vertebrae/surgery* ; Spinal Fusion/methods* ; Treatment Outcome ; Pain, Postoperative ; Muscles ; Minimally Invasive Surgical Procedures/methods*

Objective: To explore the relevant factors of work-related musculoskeletal disorders (WMSDs) among dentists through Meta analysis, providing a basis for the prevention and control of WMSDs among dentists. Methods: In April 2022, cross-sectional research literatures on the prevalence correlation of WMSDs among Chinese dentists were searched in databases such as China National Knowledge Infrastructure, Wanfang, VIP, PubMed, Web of Science, and Em Base database. The search was conducted from the establishment of the database until April 2022, literatures were selected using keywords such as musculoskeletal disorders and dentists. To extract gender, age, length of service, disease classification and other related influencing factors as indicator, and prevalence was selected as the outcome indicator. After evaluating the quality of the literatures, RevMan 5.3 software was used to calculate the combined RD (95%CI) values of the included literatures. Results: A total of 15 articles were included, with a total sample size of 3646 people. Meta analysis results showed that the prevalence of WMSDs among dentists in China was 80%, and the top three parts of the incidence rates were 65% of the waist, 58% of the neck, and 50% of the back. Gender, age, length of service, region and disease classification all increased the risk of WMSDs, and the combined effect size were 75%, 78%, 71%, 77% and 82% respectively (P<0.05) . Conclusion: The occurrence of WMSDs among dentists in China is related to multiple factors such as gender, age, length of service and disease classification. The above risk factors should be taken into account in the workplace and preventive measures should be actively implemented to prolong the working life of dentists.
Humans ; Prevalence ; Cross-Sectional Studies ; Occupational Diseases/epidemiology* ; Surveys and Questionnaires ; Musculoskeletal Diseases/epidemiology* ; Risk Factors ; China/epidemiology* ; Dentists

Objective Based on the incidence and mortality of gastric cancer and the correlation with helicobacter pylori (Hp) infection in Enshi Tujia and Miao Autonomous Prefecture from 2011 to 2020, the prevalence trend of gastric cancer in this decade was analyzed, providing theoretical basis for the prevention and treatment of gastric cancer in Enshi Tujia and Miao Autonomous Prefecture. Methods According to the unified national examination and evaluation standards, 15 tumor registries meeting the requirements were selected in Enshi Tujia and Miao Autonomous Prefecture. The incidence and death data of gastric cancer were collected, and the incidence and death rates were analyzed by gender and age. The normalized incidence rate and Hp positive rate of enshi city, Lichuan city and six counties including Jianshi, Badong, Xuan 'en, Xianfeng, Laifeng and Hefeng were compared. Spearman correlation analysis was used to analyze the correlation between standard incidence rate and Hp positive rate of gastric cancer in each district of Tujia and Miao Autonomous Prefecture of Enshi Prefecture. Results Both male and female had an upward trend. The average rate of standard incidence of gastric cancer in male and female was 4.07% and 4.15%, respectively, and there was no significant difference in the trend of standard incidence rate in different genders (P>0.05). The gross death rates and standardized death were decreased in both male and female. The average decreasing rate of standardized death rate of gastric cancer in males and females was -3.91% and -4.12%, respectively, and there was no significant difference in the trend of standardized death rate in different genders (P>0.05). Overall, the incidence rate in age group 50-80 from 2016 to 2020 was significantly higher than that from 2011 to 2015 (P<0.05). The mortality rate in the 60-80 age group from 2016 to 2020 was significantly lower than that from 2011 to 2015 (P<0.05). The trend of morbidity and mortality in different age groups was consistent in the two periods. There was a positive correlation between the incidence standard rate of gastric cancer and Hp positive rate (r =0.473, P<0.05). Conclusion From 2011 to 2020, the incidence and mortality of gastric cancer in Enshi Tujia and Miao Autonomous Prefecture were both at a high level, with an upward trend and a downward trend. The positive rate of Hp and the new infection rate of Hp in the high incidence area of gastric cancer were higher than those in the low incidence area.