In vitro cytological comparison of osseointegration properties between biomimetic bone trabecular and regular porous structure / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of biomimetic bone trabecular with the same porosity and pore size and regular porous structure on the adhesion, proliferation, and differentiation of osteoblasts, so as to provide theoretical basis for the improvement of osseointegration performance of titanium alloy implants. 【Methods】 The biomimetic bone trabecular and regular porous structures with the same porosity and pore size were generated by computer-aided software, and then processed into disc-shaped Ti6Al4V scaffolds with a diameter of 10 mm and a height of 3 mm by selective laser melting technology. MC3T3-E1 cells, the precursor cells of mouse osteoblasts in the logarithmic growth phase, were seeded on two kinds of scaffolds and divided into biomimetic bone trabecular group and regular porous structure group. After 3 hours of culture, acridine orange staining and phalloidin /DAPI staining were used to evaluate the number of cell adhesion. After 3 days of culture, the scaffolds were examined by scanning electron microscopy to evaluate the adhesion state of cells. After 1, 3, and 5 days of culture, the scaffolds were taken for CCK8 detection to observe the proliferation of cells. After 7 and 14 days of differentiation, alkaline phosphatase (ALP) activity was detected. After 14 days of differentiation, the expressions of osteogenesis-related genes (ALP, OCN, RUNX2) were detected by RT-PCR. After 30 days of differentiation, the scaffolds were stained with alizarin red and 100 g/L cetylpyridinium chloride was used to dissolve mineralized nodules. Calcium salt deposition was qualitatively and quantitatively detected to evaluate cell differentiation. 【Results】 The results of acridine orange and phalloidin /DAPI staining showed that the biomimetic trabecular Ti6Al4V scaffold adhered to more MC3T3-E1 cells than the regular porous structure, and the cytoskeleton of the former scaffold was more densely distributed. The results of scanning electron microscopy showed that the pseudopodia of MC3T3-E1 cells on the biomimetic bone trabecular Ti6Al4V scaffold were longer and the extension state was better than that of the regular porous structure. CCK8 test showed that the proliferation of MC3T3-E1 cells on the biomimetic trabecular bone titanium alloy scaffold was significantly higher than that on the regular porous structure on the 3rd and 5th day, and the difference gradually increased with the increase of time, with statistical significance (P<0.05). The results of cell differentiation test showed that ALP activity on the bionic trabecular scaffold was higher than that on the regular porous structure (P<0.05). The expressions of osteogenic genes (ALP, OCN, RUNX2) in MC3T3-E1 cells on the biomimetic bone trabecular titanium alloy scaffold were significantly higher than those on the regular porous structure (P<0.05). After 30 days of induction, the amount of calcium salt deposited in the bionic trabecular titanium alloy scaffold was significantly larger than that in the regular porous structure (P<0.05). 【Conclusion】 The biomimetic bone trabecular with a porosity of 65% and an equivalent pore size of 600 μm is more conducive to the adhesion, proliferation and differentiation of mouse osteoblast precursor cells MC3T3-E1 on the titanium alloy scaffold than the regular porous structure with the same porosity and pore size. It is theoretically more conducive to improving the osseointegration performance of titanium alloy implants.

Advances in the Diagnosis and Treatment of Rare Cardiovascular Diseases / 罕见病研究

The onset of rare cardiovascular diseases is early and the mortality is high. The patients of the disease face a long time of hardship in diagnosis and a low treatment rate. As a result, it is urgent to improve the diagnosis and treatment level of rare diseases and to accelerate the selection and R&D of drugs of rare cardiovascular diseases. In recent years, with the rapid development of new technology and basic research, the diagnosis and treatment of rare cardiovascular diseases have made breakthroughs. The article summarizes the research progress in diagnosis and treatment of rare cardiovascular diseases and looks into the future of the research.

Potential categories of health risk behaviors of college students in Wuling Mountain Area and its association with campus bullying / 中国学校卫生

Objective@#To understand the potential categories of harmful behaviors of college students in Wuling Mountain Area and its relationship with campus bullying, so as to provide a theoretical basis for promoting the development of college students physical and mental health.@*Methods@#The stratified random cluster sampling method was used to select 3 042 college students from six universities in Wuling Mountain Area from October to December, 2022. The "Chinese Youth Health Related/Risk Behaviors Questionnaire" (University Edition) compiled by the National Youth Health Related/Risk Behaviors Survey Group was used to investigate the health risk behaviors. The potential category analysis method was used to analyze the food preference, insecurity, fighting, loneliness, depression, insomnia, heartbreak, suicidal ideation, smoking, drinking, game addiction, Internet addiction of health risk behaviors were used to further analyze the relationship between different categories and campus bullying by using multi category Logistic regression method.@*Results@#College students in Wuling Mountain Area were classified into low risk group of category 1 (44.2%), category 2 (5.4%) substance dependent group, category 3(50.4%) emotional disorder group. The distribution of potential categories of health risk behaviors among college students was statistically significant by gender( χ 2=31.44, 11.69， P < 0.05 ). Logistic regression analysis showed that after controlling demographic variables, campus bullying was the risk factor of category 3 emotional disorder group( OR =1.88, P <0.01).@*Conclusion@#bullying. Colleges and universities should attach great importance to the occurrence of campus bullying, formulate intervention programs for different categories of health hazard behaviors, and promote the healthy development of college students physical and mental health.

Clinical study on the treatment of gastrointestinal neurosis with insomnia by combination of "stomach ten acupuncture" and domperidone tablets / 国际中医中药杂志

Objective:To study on the effect of "stomach ten acupuncture" combined with domperidone tablets on clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia based on the theory of "stomach harmonious leading to restless".Methods:Randomized controlled trial. From March 2020 to March 2021, 98 patients with gastrointestinal neurosis and insomnia in our hospital who met the inclusion criteria were randomly divided into two groups, with 49 patients in each group. The control group took domperidone tablets orally, and the observation group was treated with "stomach ten acupuncture" on the basis of the control group. Both groups were treated for 8 weeks. Before and after treatment, TCM syndromes were scored, the severity of gastrointestinal symptoms was assessed with Gastrointestinal Symptom Rating Scale (GSRS), anxiety and depression were assessed with Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), and sleep quality was assessed with Pittsburgh Sleep Quality Index Scale (PSQI).Results:After treatment, the scores and total scores of epigastric pain, belching, abdominal distension, anorexia, noisy acid regurgitation, tiredness and asthenia, constipation and loose stools in the observation group were significantly lower than those in the control group ( t values were 19.61, 19.30, 23.10, 22.05, 20.43, 21.81, 20.51, 16.38, respectively, P<0.01); the scores and total scores of typical symptoms, abdominal pain symptoms, reflux symptoms, diarrhea symptoms, constipation symptoms were significantly lower than those in the control group ( t values were 10.10, 11.14, 11.04, 9.31, 11.24, 5.30, respectively, P<0.01); HAMA and HAMD scores were significantly lower than those in the control group ( t values were 6.96 and 6.85, respectively, P<0.01). The scores of time to fall asleep (1.15 ± 0.56 vs. 2.11 ± 0.75, t=7.18), time to sleep (0.92 ± 0.63 vs. 1.52 ± 1.12, t=3.27), sleep quality (1.02 ± 0.66 vs. 1.96 ± 0.80, t=6.35), sleep efficiency (0.86 ± 0.62 vs. 1.68 ± 0.85, t=5.46), sleep disorders (0.92 ± 0.36 vs. 1.48 ± 0.55, t=5.96), daytime dysfunction (0.96 ± 0.42 vs. 1.97 ± 0.87, t=7.32), hypnotics (0.98 ± 0.45 vs. 1.81 ± 0.62, t=7.58) and total scores (6.85 ± 1.47 vs. 12.73 ± 2.95, t=12.49) were significantly lower than those in the control group ( P<0.01). Conclusion:The "stomach ten acupuncture" combined with domperidone tablets can improve the clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia.

The effect of "ten needles in the stomach" treatment on sleep perception for the patients with spleen-gastric damp-heat insomnia based on the theory of "stomach upset, sleep restlessness" / 国际中医中药杂志

Objective:To explore the effect of "ten needles in the stomach" on sleep perception of patients with spleen-gastric damp-heat insomnia based on the theory of "stomach discord, then sleep restlessness", to provide references for clinical diagnosis and treatment.Methods:The study subjects were 300 patients with insomnia from the sleep department and outpatient department of Shijiazhuang Traditional Chinese Medicine Hospital. According to the random number method, they were divided into the stomach ten needle group, the diazepam group, and the stomach ten needle plus diazepam group, with 100 in each group. Among them, the stomach ten needles group received "stomach ten needles" acupuncture treatment, the diazepam group was given diazepam therapy, and the stomach ten needles plus diazepam group was given diazepam combined with "stomach ten needles" acupuncture treatment. The Pittsburgh Sleep Quality Index (PSQI) scores, the self-rating disease symptom scale (SCL-90) scores, nighttime polysomnography (PSG) monitoring indicators, and the mean sleep latency (MSL) values were compared before and after treatment in the three groups. The difference in clinical efficacy between the two groups were observed.Results:The total effective rate was 94.0% (94/100) in the combined group, 77.0% (77/100) in the diazepam group, and 85.0% (85/100) in the stomach ten needle group. There were significant differences among the three groups ( χ2=11.56, P<0.01). After treatment, the daytime dysfunction, hypnotic drugs, sleep disturbance, sleep efficiency, sleep time, sleep time, sleep quality score and total score of the combined group were significantly lower than those in the diazepam group and the stomach ten needle group ( F=5.70, 3.65, 5.23, 6.37, 3.66, 6.19, 7.54, 6.40, all Ps<0.01); The scores of SCL-90 and MSL were significantly lower than those in the diazepam group and stomach ten needle group ( F=8.97, 7.53, all Ps<0.01). In the combined group, NWAK [(1.36 ± 0.87) times vs. (2.69 ± 1.15) times, (2.11 ± 1.05) times, F=5.88], SOL [(13.62 ± 5.85) min vs. (25.06 ± 9.42) min, (19.78 ± 7.63) min, F=6.49], N1/TST [(5.69 ± 1.09)% vs. (12.65 ± 2.58)%, (8.49 ± 2.45)%, F=5.13], N2/TST [(51.07 ± 10 2.06)% vs. (58.36 ± 2.18)%, (55.61 ± 2.04)%, F=9.86] were significantly lower than those in the diazepam group and stomach ten needle group ( P<0.01), SE [(90.33 ± 2.89)% vs. (85.39 ± 2.75)%, (87.53 ± 2.69)%, F=8.36], TST [(449.32 ± 23.65) min vs. (421.66 ± 25.33) min, (431.26 ± 25.98) min, F=8.26], REM/TST [(23.87 ± 4.52)% vs. (14.52 ± 3.87)%, (18.36 ± 3.25)%, F=5.34], N3/TST [(18.69 ± 2.02)% vs. (10.31 ± 1.64)%, (14.89 ± 1.74)%, F=7.69] were significantly higher than those in the diazepam group and stomach ten needle group ( P<0.01). Conclusion:Based on the "stomach discord, sleep restlessness" theory, the ten needles on the stomach can treat insomnia and improve psychological state and sleep quality, with the functions of clearing the damp and heat of the middle joker, regulating the lifting and lowering of qi in the middle.

Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus virus diseases 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2 infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). In order to understand the mechanism of these nAbs on neutralizing SARS-CoV-2 virus infections, we have performed cryo-EM analysis and here report cryo-EM structures of the ten most potent nAbs in their native full-length IgG or Fab forms bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBD in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and their correlation with more potent neutralization and the shedding of S1 subunit.

Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution

In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the "down" conformation, indicating they are more prone to adopt this receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. Through structure and sequence comparisons, we identified critical residues in the RBD that underlie the different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes and propose that N-linked glycans serve as conformational control elements of the RBD. These results collectively indicate that strong RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.

PAX3 Promotes Proliferation of Human Glioma Cells by WNT/ß-Catenin Signaling Pathways.

The PAX3 (paired box 3) gene plays an important role in embryonic development, diseases, and cancer formation. Our preliminary studies have shown that PAX3 gene is upregulated in glioma cells, which is associated with a worse prognosis. Moreover, PAX3, by facilitating cell proliferation and invasion and inhibiting cell apoptosis, plays an oncogenic role in glioma. However, the specific molecular mechanism of PAX3 acting as an oncogene in glioma remains unclarified. In the present study, we have found that PAX3 overexpression was observed in high grade glioma and predicted a worse prognosis. PAX3 overexpression did not correlate significantly to IDH1 mutation and MGMT methylation. Moreover, the expression of PAX3 was positively correlated with that of ß-catenin. In U87 glioma cells, PAX3 interacted with ß-catenin, as was confirmed by CO-IP. Besides, PAX3 overexpression promoted cell proliferation and cell cycle progression, while it inhibited cell apoptosis by altering the expressions of important molecules associated with the Wnt signaling pathway, including ß-catenin, Myc, VEGF, cyclinD1, MMP7, and Wnt1. In the meantime, it was also proved that PAX3 correlated to ß-catenin through a negative regulatory mechanism with respect to the promotion of U87 glioma cell proliferation and cell cycle progression and inhibition of the cell apoptosis. Our experiment demonstrated the role of PAX3 in promoting glioma growth and development, possibly by interacting directly with ß-catenin and regulating the Wnt signaling pathway.

Diagnostic value of the combinations of bronchoalveolar lavage fluid galactomannan test and serum galactomannan test in invasive pulmonary aspergillosis / 中华危重病急救医学

Objective To evaluate the accuracy and diagnostic value of bronchoalveolar lavage fluid galactomannan test (BALF-GM) combined with serum GM test on invasive pulmonary aspergillosis (IPA). Methods 190 cases of BALF-GM and 4 787 cases of serum GM specimens suspected of fungal infection in patients admitted to Affiliated Hospital of Jining Medical University from January 2016 to June 2018 were enrolled and analyzed. All patients were classified into clinically confirmed IPA, clinically diagnosed IPA, suspected IPA and excluded IPA according to the classification standard of Expert consensus on diagnosis and treatment of pulmonary mycosis. The coincidence rate of BALF and serum GM test results with clinical diagnosis was analyzed. Receiver operating characteristic (ROC) curve was performed, and the diagnostic value of BALF and serum GM test alone or in combination for IPA was evaluated. Subgroup analysis was performed in patients with normal or abnormal immune function, and the sensitivity and specificity of BALF and serum GM test were compared separately or jointly. Results The positive rate of BALF-GM was 46.8% (89/190), and 10.4% (497/4 787) on serum GM. Among them, 156 patients were both tested on BALF and serum GM. There were 44 cases with both positive in BALF and serum GM, the coincidence rate of clinical definite was 93.2% (41/44). There were 34 cases with positive BALF-GM and negative GM test in serum, and the coincidence rate of clinical definite was 64.7% (22/34). There were 56 cases positive in serum GM and negative in BALF-GM, and the coincidence rate of clinical definite was 48.2% (27/56). BALF and serum GM tests were both negative in 22 cases, and the coincidence rate of exclusion diagnosis was 90.9% (20/22). ROC curve analysis showed that the diagnostic value of BALF-GM test combined with serum GM test for IPA was better than that of BALF-GM test or serum GM test alone [area under ROC curve (AUC): 0.992 vs. 0.983, 0.976]. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.3%, 87.0%, 93.2% and 90.9%, respectively. Subgroup analysis showed that among 89 patients with positive BALF-GM test, 85 cases (95.5%) had normal immune function and 4 cases (4.5%) had unknown condition. Among 497 patients with positive serum GM test, 12 cases (2.4%) had normal immune function, 372 cases (74.9%) had abnormal immune function and 113 cases (22.7%) were uncertain. It was shown by ROC curve analysis that the sensitivity of positive BALF-GM test in diagnosis of IPA in patients with normal immune function was higher than that of positive serum GM test (95.6% vs. 88.9%), while the sensitivity of positive serum GM test in patients with abnormal immune function was higher than that of positive BALF-GM test (91.8% vs. 89.9%). Conclusion The results of BALF and serum GM tests are in good agreement with clinical diagnosis, and the combined detection of BALF and serum GM is more valuable for IPA diagnosis than single detection, especially for patients with unknown immune function.

Clinical study for stroke treated with meridian-collateral diagnosis and therapy by / 中国针灸

<p><b>OBJECTIVE</b>To compare the effect difference for stroke between meridian-collateral diagnosis and therapy byand conventional acupuncture with syndrome differentiation.</p><p><b>METHODS</b>Totally 148 patients were assigned into an observation group(72 cases) and a control group(76 cases) by random number table,with 10 cases dropping out in the observation group. In the observation group,meridians were examined and differentiated and then the treating meridians and acupoints were defined. Corresponding acupuncture was used according to them. In the control group,acupuncture was applied at acupoints by internal differentiation and experience. Treatment was given once a day and five times a week,with total 20 times. The motion function of limbs and coloboma degree of nerve function were assessed by Fugl-Meyer score and National Institutes of Health Stroke Score(NIHSS) before and after treatment as well as at three-month follow-up.</p><p><b>RESULTS</b>After treatment,the Fugl-Meyer scores increased and the NIHSS scores decreased in the two groups compared with those before treatment(all<0.05). At follow-up three months after treatment,Fugl-Meyer score upgraded in the observation group (<0.05) and NIHSS score declined in the two groups (both<0.01) than those before treatment,and NIHSS scores were statistically different between the two groups(<0.05).</p><p><b>CONCLUSIONS</b>Meridian-collateral diagnosis and therapy byhas better long-term efficacy when it is compared with conventional acupuncture with syndrome differentiation for motion function of limbs and nerve function of stroke.</p>

Effects of intracellular osmolality changes on the voltage-gated sodium channels currents of trigeminal ganglion neuron / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the biomechanical effects of intracellular changes on the voltage-gated sodium channels (VGSCs) on trigeminal ganglion neuron (TRGN).</p><p><b>METHODS</b>TRGN cells were acutely isolated from the neonatal SD rats. The voltage-dependent currents of the VGSCs on these neurons were elicited and analyzed by whole-cell patch-clamp recordings and the intracellular anisotonicity stimuli was established by adjusting the content of pipette solution. The effects of hypo-(260 mOsm) and hypertonic (350 mOsm) osmolarity on the activation and inactivation kinetics of VGSCs on TRGN were evaluated, compared with the normal intracellular environment.</p><p><b>RESULTS</b>The results demonstrated that intracellular hypotonic stimuli could influence both the activation and inactivation characteristics of VGSCs currents, including the membrane potential at half inactivation (V0.5) of the G-V and inactivation curves had obvious statistics significance (P<0.05) between hypotonicity (260mOsm) and isotonicity (306mOsm). However, only inactivation properties changed under intracellular hypertonic effects, including inactivation rate and k value.</p><p><b>CONCLUSION</b>It suggests that the kinetics of VGSCs on TRGN can be modulated both by intracellular hypo- and hypertonic with different characteristics.</p>

Clinical Study on Acupuncture Effect for Spastic Paralysis Following Cerebrovascular Disease / 针灸推拿医学（英文版）

Objective: To investigate the acupuncture effect for post-apoplectic spasticity.Methods: Modified Ashworth spasticity rating, Brunnstrom grades, Barthel ADL (Activity of Daily Living) indexes were employed to assess the spasticity, motor function and activities of daily living (ADL), and thus observe the effect of combined scalp and body acupuncture for post-apoplectic hemiplegic patients. Results: Combined scalp and body acupuncture can obtain significantly better effects than body acupuncture alone in relieving spasticity and improving the patients' motor function and ADL (P＜0.01). Conclusion: Combined scalp and body acupuncture has a distinct advantage in relieving spasticity and can improve the patients' motor function and ADL.

PFD Test in SLE & DM Cases for Determination of Pancreatic Exocrine Function / 第三军医大学学报

Pancreatic function diagnostant test (PFD) is performed with the oral administration of N-benzoyl-L-tryosyl-P-aminobenzoic acid (BT-PABA) .It is a specific test for the determination of the exocrine function of the pancreas. It can be more reliable if P-aminobenzoic acid absorbing test (PABA) is also performed to eliminate the intestinal, hepatic, and renal factors in PABA absorption and excretion.The authors used the combined method of PFD and PABA to study the pancreatic exicrine function in 32 cases of systemic lupus erythematosus (SLE) and 16 cases of dermatomyositis (DM) . It was found that lowed exocrine function of the pancreas occurred in 9.4% of SLE cases and in 18.8% of DM cases though no definite abdominal symptoms or signs could be observed in those cases. It is suggested that the combined PFD and PABA method be used in early SLE and DM cases to evaluate the pancreatic exocrine function.