OBJECTIVE: This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats. METHODS: Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed. RESULTS: BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05). CONCLUSION: BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats. UNLABELLED The graphical abstract is available on the website www.besjournal.com.
Rats ; Male ; Animals ; Leydig Cells/metabolism* ; Testosterone ; Glycogen Synthase Kinase 3 beta/pharmacology* ; Rats, Sprague-Dawley ; Sexual Maturation ; Testis ; Oxidative Stress ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

ObjectiveTo explore the guidance value of “treatment of disease in accordance with three conditions” theory in the prevention and treatment of corona virus disease 2019（COVID-19） based on the differences of syndromes and traditional Chinese medicine（TCM） treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. MethodDemographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system （HIS） of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. ResultA total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai，dominated by young and middle-aged males，had clinical symptoms of fever， abnormal sweating，and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat， with manifest cold， dampness， and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness， accompanied by draining depressed heat. The core Chinese medicines used are Poria，Armeniacae Semen Amarum，Gypsum Fibrosum，Citri Reticulatae Pericarpium，and Pogostemonis Herba. By contrast，the 105 patients in Ruili， dominated by young females， had atypical clinical symptoms， and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach， with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen， resolving dampness， and dispersing Qi with light drugs. The core Chinese medicines used are Poria，Atractylodis Macrocephalae Rhizoma，Glycyrrhizae Radix et Rhizoma，Coicis Semen，Platycodonis Radix，Lonicerae Japonicae Flos， and Pogostemonis Herba. ConclusionThe differences in clinical characteristics， TCM syndromes， and medication of COVID-19 patients from the two places may result from different regions，population characteristics， and the time point of the COVID-19 outbreak. The “treatment of disease in accordance with three conditions” theory can help to understand the internal correlation and guide the treatments.

OBJECTIVE: To study the clinical effect of individualized controllable stress external fixator in the treatment of open tibial fractures. METHODS: From December 2018 to July 2020, 60 patients with open tibial fractures were treated, including 35 males and 25 females;The age ranged from 23 to 58 years;The course of disease was 1.2 to 10.0 h. According to the stress stimulation on the fracture end after operation, all patients were divided into 4 groups, including non stress group (15 cases) and 3 groups with different stress stimulation(15 cases in each group). All patients with open tibial fractures were treated with controllable stress external fixator. Four weeks after operation, the stress group adjusted the elastic external fixator to apply axial stress of 1/6, 2/6 and 3/6 of their own weight to the fracture end based on the patient's weight. The wound healing of all patients after operation was observed, the plain CT images of fracture ends at 4, 6, 8, 10 and 12 weeks after operation were followed up, the average valueof callus area per 10 scanning planes was calculated, and the differences between the groups were compared. The fracture healing was observed and statistically analyzed. RESULTS: The wounds of all patients healed well, of which 7 patients underwent secondary free skin grafting and transferred myocutaneous flap. All patients were followed up for 12 to 24 months, with an average of 16.5 months. The final follow-up results showed that the fracture healing of stress groups and non stress group had significant difference( CONCLUSION When the controllable stress external fixation technique is used to treat open tibial fractures, the elastic external fixator is adjusted according to the patient's own weight after 4 weeks, and a certain axial stress is applied to the fracture end, which is conducive to the fracture healing of patients, and can reduce the incidence of delayed union or nonunion of open fractures, which has a certain application value.
Adult ; External Fixators ; Female ; Fracture Fixation ; Fracture Healing ; Fractures, Open/surgery* ; Humans ; Male ; Middle Aged ; Tibial Fractures/surgery* ; Treatment Outcome ; Young Adult

The processing of Aurantii Fructus has a long history and many methods. In addition to the current mainstream varieties of raw products and stir-fried products with bran of Aurantii Fructus, other 17 processing methods, such as stir-fried with rice, processed with salt, honey and medicinal juice, are recorded in the literature of past dynasties. Through a comprehensive review and sorting out of ancient and modern literature, this paper clarifies the historical evolution of the processing of Aurantii Fructus, through clarifying the historical evolution of processing and analyzing the present situation of modern research on Aurantii Fructus, summarizes the modern research progress on processing in production place, processing technology, chemical compositions and pharmacological effects before and after being processed, and puts forward some ideas for the follow-up research on processing of Aurantii Fructus, in order to provide reference for screening the dominant varieties, standardizing the processing technology, explaining the scientific connotation of processing, and improving the utilization ratio of medicinal resources of Aurantii Fructus.

BACKGROUNDThe established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI).

METHODSTaking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT.

RESULTSThe median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3-6]) with significantly different TTFT (median TTFT of not reached (NR), 65.0 months, 36.0 months and 19.0 months, respectively, P < 0.001).

CONCLUSIONSThis study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers with traditional clinical stage. This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.

Adult ; Aged ; Aged, 80 and over ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 17 ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Immunoglobulin Heavy Chains ; genetics ; metabolism ; In Situ Hybridization, Fluorescence ; Leukemia, Lymphocytic, Chronic, B-Cell ; diagnosis ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Prognosis

"Wise men could recognize similarities, but the fool only recognizes differences" in Su-wen, which expounded clinical thinking methods of Chinese medicine (CM). "To recognize similarities and differences simultaneously" is of important clinical significance in understanding the laws of diseases. CM pays much attention to recognize similarities, while modern medicine emphasizes the differences observed. In order to develop integrative medicine (IM), similarities recognition and differences identification must be combined together to innovate new thinking methods of IM.
Humans ; Integrative Medicine ; standards ; Medicine, Chinese Traditional

OBJECTIVETo study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques.

METHODSTwo hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis.

RESULTSThe positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis.

CONCLUSIONSVEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.

Aged ; Biomarkers, Tumor ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Microsatellite Instability ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Receptor, ErbB-2 ; metabolism ; Receptors, CXCR4 ; metabolism ; Rectal Neoplasms ; metabolism ; pathology ; Retrospective Studies ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-3 ; metabolism

Aged ; Animals ; China ; epidemiology ; Disease Outbreaks ; Female ; Humans ; Male ; Middle Aged ; Orientia tsutsugamushi ; Scrub Typhus ; epidemiology

OBJECTIVETo measure the pressure changes inside the cervical nucleus pulposus in fresh human cervical specimen by imitating different rotary manipulations.

METHODSThe load of 100 N was applied for 5 second on the six fresh male cervical samples by using material test system, which imitated the human head weigh and the strength of cervical extensor muscle. After that, traction, rotation and pulling on the samples were performed in different sequence under the force of 150, 200, 300 N respectively. Three states were included in adding the load state A: samples were loaded with traction and then rotation to the biggest angle, pulling backward for 15 degrees; state B: samples were loaded with rotary stress to the biggest angle and then loaded with traction, pulling backward for 15 degrees; state C: samples were loaded simultaneously with traction and rotary stress to the biggest angle, pulling backward for 15 degrees. The internal pressure of cervical nucleus pulposus at segment of C(3,4), C(4,5), C(5,6), and C7 was measurred by micro-pressure sensors for state A, B, C and for the imitation of head weight and the strength of cervical extensor muscle.

RESULTSThe pressure inside the cervical nucleus pulposus at segments C(5,6), C(6,7) was higher than that at segments C(3,4) and C(4,5) (P < 0.05) by loading stress with 100 N for 5 seconds. The internal pressure of the nucleus pulposus decreased with the increase of traction (P < 0.05), and increased when traction and rotary force were loaded. State A, the value of increased pressure within the nucleus pulposus became smaller and smaller while increasing of the traction force loaded (P < 0.05). State B, the increase of internal pressure in nucleus pulposus became obvious as loading pressure increased (P < 0.05). State C, the internal pressure in nucleus pulposus was not increased obviously (P > 0.05). There was a transitional pressure raise inside all cervical nucleus pulposus when pulling added after different sepuence traction and rotary strength was applied, however, the internal pressure of state A was significantly higher than that of state B or C (P < 0.05). There was also a transitional pressure raise inside all cervical nucleus pulposus when pulling added in different strength (P < 0.05),the internal pressure by pulling with 150 N was obviously higher than that with 200 N and 300 N (P < 0.05).

CONCLUSIONThe order of rotation first and traction second should be avoided when practice of rotary manupuplation in case protrusion of the nucleus pulposus. Meanwhile, proper traction should be applied along with rotary manipulation in order to increase its safety.

Adult ; Cervical Vertebrae ; Humans ; Intervertebral Disc ; Male ; Musculoskeletal Manipulations ; adverse effects ; methods ; Pressure ; Rotation ; Stress, Mechanical ; Young Adult

BACKGROUNDNon-cement femoral stems are recognized in clinical use, but there are still some problems. The aim of this research was to make non-cement femoral stems to be press-fit with the medullary cavity.

METHODSTwenty-four healthy adult mongrel dogs were randomly divided into experimental and control groups. In the right hip joint, an artificial femoral bone replacement surgery was conducted. For the experimental group, the replacement surgery of hydroxyapatite (HA)-coated femoral stems was done, while autogeneous morselized bone was implanted into the medullary cavity. For the control group, morselized bone was not implanted. At postoperative 1, 3, 6 months, a test for interfacial shear characteristics was conducted in the MTS810 Tester. The comparison between the two groups' bone-prostheses in shear strength for their interface from shearing destruction was made. A histological observation to check prosthesis-bone interface contact ratios and bone growth was carried out.

RESULTSFor the experimental group, shear strength was 0.317 MPa in 1 month, 1.447 MPa in 3 months, and 1.621 MPa in 6 months. For the control group, shear strength was 0.195 MPa in 1 month, 1.023 MPa in 3 months, and 1.483 MPa in 6 months. The difference was statistically significant. Stereomicroscope-based observation showed that the number of trabecular bones in the experimental group was larger than that of the control group, and bone growth of the former group was better than that of the latter group. Inverted microscopic observation showed that the binding degree between the prosthesis and trabecular bone of the experimental group was higher than that of the control group. Comparatively, the experimental group's trabecular bone had more stromal cells.

CONCLUSIONSThe morselized bones can effectively improve the biological bonding strength and bone-contact ratios in the short term for the HA-coated femoral stem and accelerate the bonding process. The use of morselized autogenous bones played a good role in bone in-growth of the femoral bone stem surface.

Animals ; Biomechanical Phenomena ; Coated Materials, Biocompatible ; chemistry ; Dogs ; Durapatite ; chemistry ; Female ; Femur ; pathology ; surgery ; Male ; Osseointegration ; Random Allocation ; Shear Strength