Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.
Humans ; Acupuncture Therapy ; Periosteum ; Analgesia ; Pain Management ; Consciousness ; Pain

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To explore the expression and clinical significance of EZH2 in DLBCL patients accompanied by HBV infection. METHODS: The clinicopathological data of 59 patients with DLBCL accompanied by HBV infection in our hospital from February 2015 to October 2017 were analyzed retrospectively. The patients were divided into HBV negative and HBV positive groups by serological testing before surgery. The expression of EZH2 was detected by immumohistochemical staining, and the clinicopathological characteristics and survival were analyzed and compared between these two groups. RESULTS: There were 30 patients (50.8%) in the HBV negative group and 29 patients (49.2%)in the HBV positive group. The differences of age, LDH level and IPI score between two groups were statistically significant (P＜0.05). The expression of EZH2 in HBV- positive group was significantly higher than that in the HBV- negative group (P＜0.05), where the expression of EZH2 correlated with the expression of the BCL-6 (r=0.282, P＜0.05), especially in the GCB-DLBCL (r=0.549, P＜0.05). PFS was not significantly different between two groups of HBV (P＞0.05), while the PFS in the R-CHOP regimen group was higher than that in the CHOP regimen group (P＜0.05). COX multivariate analysis showed that both the chemotherapy regimen without R and the increased level of LDH were the risk factors affecting the prognosis of DLBCL patients (P＜0.05). CONCLUSION EZH2 highly expresses in HBV positive group, suggesting that the significance of EZH2 in DLBCL with HBV infection is worth further explore.
Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Doxorubicin ; Enhancer of Zeste Homolog 2 Protein ; genetics ; Hepatitis B ; complications ; Hepatitis B virus ; Humans ; Lymphoma, Large B-Cell, Diffuse ; complications ; genetics ; Prognosis ; Retrospective Studies ; Rituximab ; Vincristine

OBJECTIVE: To study the expression of multiple negative costimulatory molecules on peripheral blood T cells in patients with acute myeloid leukemia (AML) and its affection on prognosis. METHODS: The peripheral blood samples from patients with newly diagnosed AML, complete remission (CR), and no-remission (NR) were collected, the expression levels PD-1、VISTA and TIM-3 in CD4 and CD8 T cells were detected by flow cytometry , and the clinical data of patients were analyzed. RESULTS: The expression levels of PD-1、VISTA and TIM-3 of CD4 and CD8 T cells in the newly diagnosed AML patients were significantly higher than those in control group (P＜0.05). The expression levels of PD-1、TIM-3 and VISTA of CD4 and CD8 T cells in the CR group were significantly lower than those in newly diagnosed and the NR group (P＜0.05). The TIM-3 expression level positively correlated with VISTA expression level of CD4 and CD8 T cells in newly diagnosed AML patients (r=0.85 and 0.73). The VISTA and PD-1 expression level of CD4 T cells in newly diagnosed AML, NR after first induction chemotherapy and high risk patients significantly increased (P＜0.05), the TIM-3 expression level of CD8 T cells in high risk group significantly increased (P＜0.05), and the VISTA expression level of CD8 T cells in CBFβ-MYH11 mutation-positive group significantly decreased (P＜0.05). CONCLUSION The expression of PD-1、TIM-3 and VISTA in AML peripheral blood T cells may be involved in the immune escape of AML and can be the targets of treatment for acute myeloid leukemia patients.
B7 Antigens ; CD8-Positive T-Lymphocytes ; Flow Cytometry ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Leukemia, Myeloid, Acute ; Programmed Cell Death 1 Receptor

OBJECTIVE: To investigate the relationship of cytogenetic features, clinical characteristics and prognosis in patients with myelodysplastic syndrome. METHODS: The clinical characteristics and prognosis of 236 patients with MDS admitted to the Affiliated Hospital of Xuzhou Medical University from January 2013 to September 2017 were analyzed retrospectively, the follow-up observation and correlation analysis were performed. RESULTS: There were 33 cases of refractory cytopenia with unilateral dysplasia (RCUD), 8 cases of refractory anemia with ring-shaped iron granulocytes (RARS), 70 cases of refractory cytopenia with multiple dysplasia (RCMD), 23 cases of refractory anemia (RA), 46 cases of refractory anemia with excessive blasts (RAEB-1), 48 cases of (RAEB-2), MDS-U 2 cases, simple del(5q) 6 cases. The detection analysis showed that the chromosome abnormality rate and complex chromosome abnormality rate in RAEB group (RAEB-1 + RAEB-2) and in non-RAEB group (RARS+RCMD+RCUD+RA) were 48.94% vs 43.94%, and 18.09% vs 12.69%, respectively, which were no statistically different. The grouping according to IPSS-R and IPSS showed that the chromosome abnormality rate gradually increased along with enhancement of risk stratifi-cation (P<0.05). The cytogenetic characteristics analysis showed that a total of 108 cases had chromosomal abnormalities, the detection rate was 45.76%, Out of 108 cases, 36 cases had complicated karyotypes, accounted for 15.25% of all patients. The types of chromosomal abnormalities mainly include numbers, structural abnormalities and mixed abnormalities. The chromosome abnormality with the highest detection rate was +8, accounted for 30.56% (33/100) of patients with chromosome abnormalities; followed by -7/7q-, del(5q), del(20q), etc. -7/7q-chromosome abnormalities accounted for 29.63% of all karyotypic abnormalities (including -7/7q-chromosome abnormalities alone and other chromosome abnormalities). The median age of the patients with MDS was 61 (13-88) years old, and the male-female ratio was 1.36∶1. Analysis of blood cell characteristics showed that the three lines were reduced or increased to varying degrees. The median WBC count was 2.8 (0.3-267.1)×10/L, the median Hb level was 69 (20-156) g/L, and the median Plt count was 55 (2-1733)×10/L. The 1 year OS rate in 32 cases of chromosome 7 abnormality and 128 cases of normal chromosome was 25% and 44.53%, respectively, the difference was statistically significant (χ=4.05, P<0.05) . CONCLUSION Chromosome karyotype is an independent factor affecting the prognosis of patients with MDS. It is important for the diagnosis, treatment and prognosis evalnation of patients with MDS. The overall prognosis of patients with abnormal chromosome 7 is poor. .
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Cytogenetics ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Myelodysplastic Syndromes ; Prognosis ; Retrospective Studies ; Young Adult

Introduction:Right-sided colon cancer (RSCC) and left-sided colorectal cancer (LSCRC) differ with respect to their biology and genomic patterns. This study aimed to examine whether the primary tumor location is associated with the response to cetuximab in patients with metastatic colorectal cancer (mCRC). Methods:Patients with mCRC treated with cetuximab and standard chemotherapy as first-or second-line treatments were compared with randomly chosen patients who were treated with chemotherapy alone between 2005 and 2013. The main outcome measures were the overal response rate (ORR), progression-free survival (PFS), and overal survival (OS). The differences in the outcome were analyzed by using the chi-squared test, Student’s t test, and Kaplan-Meier method. Results:The treatment results of 206 patients with mCRC treated with cetuximab and standard chemotherapy as first-or second-line treatments were compared with those of 210 patients who were treated with chemotherapy alone. As a first-line treatment, cetuximab with chemotherapy was associated with a significantly higher ORR (49.4%vs. 28.6%, P=0.005) as well as longer PFS (9.1 vs. 6.2 months, P=0.002) and OS (28.9 vs. 20.1 months, P=0.036) than chemotherapy alone in patients with LSCRC. However, cetuximab neither improved the ORR (36.4%vs. 26.2%, P=0.349) nor prolonged PFS (5.6 vs. 5.7 months, P=0.904) or OS (25.1 vs. 19.8 months, P=0.553) in patients with RSCC. As a second-line treatment, cetuximab exhibited a tendency to improve the ORR (23.5%vs. 10.2%, P=0.087) and prolong PFS (4.9 vs. 3.5 months, P=0.064), and it significantly prolonged OS (17.1 vs. 12.4 months, P=0.047) compared with chemotherapy alone in the patients with LSCRC. In contrast, as a second-line treatment, cetuximab neither improved the ORR (7.1%vs. 11.4%, P=0.698) nor prolonged PFS (3.3 vs. 4.2 months, P=0.761) or OS (13.4 vs. 13.0 months, P=0.652) in patients with RSCC. Conclusions:The addition of cetuximab to chemotherapy in both first-and second-line treatments of mCRC may only benefit patients with primary LSCRC.

Early Diagnosis ; Hepatitis, Autoimmune ; diagnosis ; therapy ; Humans

UNLABELLEDTo explore the clinical and pathological features of male and female autoimmune hepatitis (AIH) patients.

METHODSOne hundred and sixty-nine AIH patients were enrolled. The clinical and histological data of the male cases were compared with the female ones.

RESULTSThere were 23 (13.6%) male patients in our study. The general status, biochemical and immunological test, and histological findings between two groups had no significant difference (P more than 0.05). The IAIHG's revised original scoring system pretreatment scores of male patients (14.4+/-2.3) were lower than that of female ones (16.6+/-2.6, Z= -3.728, P=0.000), whereas the simplified scoring system scores of male patients (7.2+/-0.8) were higher than that of female ones (6.5+/-1.2, Z=-2.372, P=0.018). There were 15 male AIH patients treated with immunosuppressive therapy, then 12 of them reached complete biochemical remission, the other three cases were incomplete response. The complete biochemical remission rate in our male cases was 80%. Median duration of remission was 3 months (95% CI 2.070-3.930 months).

CONCLUSIONThere are no significant differences in clinical and pathological features of AIH between genders. The diagnosis of AIH should be suspected in male patients with any abnormality in serum aminotransferases levels. Liver biopsy examination is recommended to establish the diagnosis of AIH. The simplified criteria have good diagnostic value for male AIH patients.

Adolescent ; Adult ; Aged ; Female ; Hepatitis, Autoimmune ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Sex Factors ; Young Adult