This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.
Humans ; Animals ; Periplaneta ; Sirtuin 1/genetics* ; K562 Cells ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Mammals

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Cognition ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Monocytes/pathology* ; Polysaccharides/therapeutic use* ; Proteoglycans

OBJECTIVE: To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS: In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS: Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Moxibustion ; Osteoarthritis, Knee/therapy* ; Treatment Outcome

OBJECTIVE: To analyze the change of serum C1q in the course of multiple myeloma (MM) and its correlation with clinical characteristics. METHODS: A total of 138 newly diagnosed MM patients in Zhongnan Hospital of Wuhan University from June 2016 to December 2019 were selected as research objects, during the same period 50 age-matched anemia patients, 50 lymphoma patients, 50 leukemia patients, and 50 myelodysplastic syndrome (MDS) patients were selected as control groups. All the patients met WHO disease classification, and were definitely diagnosed by pathology or bone marrow smear/biopsy. The changes of C1q between MM patients and control group, as well as in different therapeutic responses of MM patients before and after treatment were compared, also the difference of clinical characteristics among MM patients with different C1q level, so as to analyze risk factors which led to C1q decline. RESULTS: The average value of C1q in MM patients was (128.18±51.24) mg/L, which was significantly lower than control group (P<0.01). The levels of white blood cell, platelet (PLT), hemoglobin (Hb), serum calcium, albumin, lactate dehydrogenase (LDH) in newly diagnosed high C1q group were significantly higher than those in low C1q group (P<0.05). Logistic analysis showed that the levels of PLT, Hb, albumin, and LDH in newly diagnosed high C1q group were higher than those in low C1q group (r=0.248, r=0.394, r=0.405, r=0.295). After treatment, the levels of C1q in MM patients with complete remission and very good partial remission were significantly higher than before treatment (P<0.05), while those with partial remission and stable disease also increased but not significantly (P>0.05). CONCLUSION The C1q level in MM patients is significantly lower than that in patients with other hematologic system diseases, and it increases with the remission of the disease after treatment.
Albumins ; Bone Marrow ; Complement C1q ; Humans ; Multiple Myeloma ; Risk Factors

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, CONCLUSIONS Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia ; Asphyxia Neonatorum/epidemiology* ; Humans ; Hyperglycemia ; Infant, Newborn ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the effect of total hip arthroplasty(THA) with the prosthesis of 127° small neck stem angle and 135° large neck stem angle. METHODS: From January 2014 to June 2016, 84 patients with THA were selected, including 44 males and 40 females, aged 45 to 72(53.4±8.1) years old, 68 patients with necrosis of the femoral head(32 on the left and 36 on the right), 16 patients with serious osteoarthritis of the hip caused by other reasons, and the course of disease was 9 to 36 (24.0±5.5) months. Forty-two patients in each group were evaluated by Harris score, visual analog score(VAS), length measurement of lower limbs, biomechanical evaluation of different angles of the neck stem. The complications and quality of life 24 months after operation were compared. RESULTS: Two patients in each group were lost, the rest were followed up for 30 to 36 (33.0±1.6)months. The Harris score and the length of both lower limbs were measured before and 1, 6, 12, 24 months after operation. The difference of Harris score and the length of both lower limbs in the two groups was significantly improved compared with that before operation( CONCLUSION THA with large and small neck stem angle prosthesis can better recover the function of hip joint, but large neck stem angle can reduce the degree of postoperative pain and improve the quality of life of patients.
Aged ; Arthroplasty, Replacement, Hip ; Female ; Hip Joint/surgery* ; Hip Prosthesis ; Humans ; Male ; Middle Aged ; Quality of Life ; Retrospective Studies ; Treatment Outcome

Objective To investigate the influencing factors for liver cancer by gender in Shunde region, and to explore the potential interactions among influencing factors for liver cancer in males. Methods The relative excess risk of interaction (RERI) and other indices were used to evaluate the pair-wise interaction, and the classification and regression tree (CART) model was applied to explore the potential multi-factors interaction. Results This study included 1 037 male cases and 1 069 controls, together with 166 female cases and 185 controls. Chronic hepatitis B virus infection (CHB) and family history of liver cancer were significantly associated with increased risk of liver cancer both in males and females (both P<0.001). In males, positive additive interactions were observed between CHB and smoking or alcohol drinking, as well as between smoking and drinking. The RERI for CHB and smoking was 121.90(95% CI：52.85%-190.95%). Negative additive interactions were observed between exercise and CHB or smoking. Further, the CART analysis suggested that the CHB males who smoked and drank alcohol had the highest risk of liver cancer. Conclusions CHB and family history of liver cancer are important risk factors for liver cancer in both males and females. CHB, smoking, and alcohol drinking synergistically promote the incidence of liver cancer for males. Exercise can antagonize the hepatocarcinogenic effect of CHB and smoking.

Hepatic fibrosis is a common feature of almost all chronic liver diseases. Formation of new vessels (angiogenesis) is a process strictly related to the progressive fibrogenesis which leads to cirrhosis and liver cancer. This review mainly concerns the relationship between angiogenesis and hepatic fibrosis, by considering the mechanism of angiogenesis, cells in angiogenesis, anti-angiogenic and Chinese medicine therapies.

Objective To compare the biomechanical characteristics of new assembly of locking compression plate (NALCP) and locking compression plate (LCP) in internal fixation of femoral shaft comminuted fractures.Methods The preparation of a femoral shaft wedge fracture model (AO type 32-C2.1),six pairs of (12) femoral specimens were collected and divided into two groups randomly,with six in each group.The Group A was made up of the new assembly of locking compression plate fixation model (NALCP),and Group B the locking compression plate fixation model (LCP).The biomechanical properties of steel plates in two groups were tested by axial loading and torsional loading tests.The relative maximum displacement of fracture blocks in two groups on the X,Y and Z axes (the coronal axis was set as X axis,through the medial and lateral femur;the transverse axis was set as Z axis,through the femoral intercondylar fossa,perpendicular to the X axis;the sagittal axis was set as Y axis,perpendicular to the X and Z axis),the maximum strain,and the average strain of the steel plate were recorded.Strain distribution nephogram was produced,and the axial loading fatigue test results of Group A were recorded.Results Axial loading test:the relative maximum displacement of fracture in Group A on X,Y and Z axis were smaller than those in Group B (P ＜0.05 or 0.01);the main strain of Group A was greater than that of Group B (P ＜0.01);there was no significant difference in the average strain between Group A and Group B (P ＞ 0.05).Torsional loading test:The relative maximum displacement of fracture in Group A on X and Z axis was smaller than that of Group B (P ＜ 0.01);there was no statistically significant difference between the two groups on the Y axis (P ＞ 0.05);the main strain of plate in Group A was greater than that in Group B (P ＜ 0.01);there was no statistically significant difference in the average strain between Group A and Group B (P ＞ 0.05).There was no obvious difference in strain distribution between the two groups.In Group A,the fatigue test of axial cyclic loading was performed for 1 million times,and the NALCP was intact without deformation,loosening,or rupture.Conclusion NALCP can provide strong mechanical stability for comminuted femoral fracture.The design of bridge steel plate is reasonable,which can effectively avoid stress concentration,reduce the stress shielding of steel plate,and facilitate bone healing.