Identification of the CCL2 PI3K/Akt axis involved in autophagy and apoptosis after spinal cord injury.

Spinal cord injury (SCI) is a devastating neurological disease with no cure that usually results in irreversible loss of sensory and voluntary motor functions below the injury site. We conducted an in-depth bioinformatics analysis combining the gene expression omnibus spinal cord injury database and the autophagy database and found that the expression of the autophagy gene CCL2 was significantly upregulated and the PI3K/Akt/mTOR signaling pathway was activated after SCI. The results of the bioinformatics analysis were verified by constructing animal and cellular models of SCI. We then used small interfering RNA to inhibit the expression of CCL2 and PI3K to inhibit and activate the PI3K/Akt/mTOR signaling pathway; western blot, immunofluorescence, monodansylcadaverine, and cell flow techniques were used to detect the expression of key proteins involved in downstream autophagy and apoptosis. We found that when PI3K inhibitors were activated, apoptosis decreased, the levels of autophagy-positive proteins LC3-I/LC3-II and Bcl-1 increased, the levels of autophagy-negative protein P62 decreased, the levels of pro-apoptotic proteins Bax and caspase-3 decreased, the levels of the apoptosis-inhibiting protein Bcl-2 increased. In contrast, when a PI3K activator was used, autophagy was inhibited, and apoptosis was increased. This study revealed the effect of CCL2 on autophagy and apoptosis after SCI through the PI3K/Akt/mTOR signaling pathway. By blocking the expression of the autophagy-related gene CCL2, the autophagic protective response can be activated, and apoptosis can be inhibited, which may be a promising strategy for the treatment of SCI.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅲ): classification of granule dissolving behaviors / 中国中药杂志

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(β-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly β-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.

Evaluation and classification of dissolution behavior and capability of Chinese medicine granules based on an inline turbidity sensor / 中国中药杂志

In this paper, the inline turbidity sensor technology was used to quantify the turbidity of the solution during the dissolution of Chinese medicine granules. The probe measurement position and the magnetic stirring speed were optimized. As a result, the stirring speed was 400 r·min~(-1), and the probe position was at 1/4 of the diameter of the beaker. The measurement results were accurate and reliable. Totally 105 batches of commercially available Chinese medicine granules were collected and dissolved according to the requirements of the Chinese Pharmacopoeia. At the time point of 5 min, 57 batches of granules were completely dissolved, and the corresponding turbidity values ranged between 0-70 FTU; 32 batches of granules showed a slight turbidity, and the corresponding turbidity values ranged between 70-350 FTU; 14 batches of granule solution were turbid, and the corresponding turbidity values ranged between 350-2 000 FTU; two batches of granule solution were heavily turbid, and the corresponding turbidity values were >2 000 FTU. Among the above results, the number of batches in line with the pharmacopoeia dissolution requirement was 84.76%, and the dissolution of some granules still needed to be improved. The turbidity sensor recorded the change curve of turbidity value over time(solubility behavior curve). The degree of important of disintegration and dissolution during the dissolution process showed disintegration > dissolution, disintegration≈dissolution, disintegration < dissolution. The dissolution behavior of the granules can be classified into three categories. The analysis of the mechanism in the process of granule solubility provides a basis for product process improvement.

Serum levels of immunoglobulins in an adult population and their relationship with nonalcoholic fatty liver disease.

OBJECTIVES: Few studies have reported the association between nonalcoholic fatty liver disease (NAFLD) and immunoglobulins. In this study, we aimed to investigate the relationship between serum immunoglobulin levels and NAFLD in a Chinese adult population. METHODS: We performed a cross-sectional study including 11 261 Chinese adults. NAFLD was diagnosed based on the Chinese Guidelines for the diagnosis and treatment of fatty liver diseases and an alcohol intake of <70 g/week in women and <140 g/week in men, and serum immunoglobulin (Ig) levels were determined using immune nephelometry. Multiple logistic regression analysis was done to assess relationships between concentrations of serum immunoglobulins and NAFLD. RESULTS: Of the 11 261 adults recruited from January 2010 to December 2015, the prevalence of NAFLD was 40.8% (n = 4598). The geometric mean levels of IgG, IgM, IgE and IgA were 1177.49 mg/dL (95% confidence interval [CI] 1173.07-1181.93), 93.56 mg/dL (95% CI 92.70-94.42), 30.70 IU/mL (95% CI 29.92-31.49) and 216.64 mg/dL (95% CI 214.95-218.34), respectively. Compared with the lowest quintile, the multivariable adjusted odds ratio (95% CI) of NAFLD for the highest quintile of IgG, IgM, IgE, and IgA were 0.78 (0.66-0.92), 0.71 (0.60-0.84), 0.98 (0.84-1.15) and 1.41 (1.21-1.66), respectively. CONCLUSION: Increased IgA and decreased IgG and IgM levels are independently associated with NAFLD prevalence. Further research is needed to explore the causal association between serum immunoglobulins and NAFLD.

[Clinical effects of internal fixation with Herbert screws for the treatment of Pipkin femoral head fractures].

OBJECTIVE: To explore the therapeutic effects of internal fixation with Herbert screws for the treatment of Pipkin type I and type II femoral head fractures. METHODS: From January 2008 to December 2012, 23 patients with Pipkin type I and type II femoral head fractures were treated with open reduction and internal fixation by Herbert screws through Kocher-Langenbeck approach. Twenty-three patients (aged 18 to 52 years with a mean of 35.5 years, including 18 males and 5 females patients, 8 left hips and 15 right hips) with femoral head fractures and posterior hip dislocation. The fracture was classified according to Pipkin classification based on the radiographic findings, 5 patients had type I and 18 had type II fractures. The duration time from admission to the operation ranged from 6 to 72 h (averaged 32 h). The clinical and radiographic outcomes of the patients were measured using Thompson-Epstein scoring scale. The Harris hip score(HHS) was used to evaluate and compare hip functions at the latest follow-up between affected and healthy sides. RESULTS: All the patients were followed up, and the duration ranged from 20 to 48 months (averaged 30 months). According to Thompson-Epstein system, 12 patients got an excellent result, 6 good, 4 fair and 1 poor. The average HHS at the finial follow-up was 87.80 ± 8.46 (ranged from 66 to 95), which is similar to that in the healthy side 90.10 ± 6.35 (ranged from 72 to 98) (t = 1.044, P = 0.302). The complications such as deep infection, and deep vein thrombosis were not found. At the 3rd year during follow-up,4 patients had avascular necrosis of femoral head. At the 1st year of follow-up, 1 patient had hip pain after walking,screws loosening and shift after trauma,and serious complications of traumatic arthritis. All the 5 patients were treated with total hip arthroplasties. CONCLUSION: The treatment of internal fixation with Herbert screws through the Kocher-Langenbeck approach is effective for Pipkin type I and type II femoral head fracture. The method is reliable and valuable for recommendation. However, such fracture may have avascular necrosis of femoral head and complication of traumatic arthritis, which should be observed carefully in clinic with preparation of the prevention and treatment measures.

[Treatment of fracture of fifth metatarsal base and degree III lateral ligament injury of ankle with compressed cannulated screw and suture anchors].

OBJECTIVE: To investigate the clinical outcomes of surgical treatment of fracture of the fifth metatarsal base combined with degree III lateral ligament injury of ankle. METHODS: From January 2008 to December 2011, 32 patients with fracture of the fifth metatarsal base combined with degree III lateral ligament injury of ankle were treated with surgery. Fractures were fixed with compressed canulated screw and ligaments were repaired with suture anchors. After operation, ankle joints were fixed in neutral position and slightly valgus position by plaster slab. Taking out stitch was performed at 2 weeks after operation and non-weight loading walking by double crutches support started; after the 6 weeks, remove the gypsum and part-weight loading walking by brace protection; at the 8 weeks after operation, completely weight loading walking was permitted. American Orthopaedic Foot and Ankle Society (AOFAS) was used to evaluate the clinical effect. RESULTS: Thirty-two patients were followed up from 8 to 18 months with an average of 12 months. All fractures obtained healing with an average time of 12.5 weeks (ranged, 8 to 24 weeks). According to the standard of AOFAS, 18 cases got excellent results and 14 good. CONCLUSION: The method that fracture fixation with compressed canulated screw and ligament repair with suture anchors can obtain satisfactory effects in treating fracture of the fifth metatarsal base and degree III lateral ligament injury of ankle.

Molida therapy in the out-patient department for patients with III B prostatitis / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the therapeutic effect of Molida therapy in the out-patient department for patients with III B prostatitis.</p><p><b>METHODS</b>One hundred and thirty-six patients with II B prostatis accompanied with psychological disorder of different degrees were divided into two groups: Group A (68 cases), treated with routine drug and Molida therapy, and Group B (68 cases), treated with routine drug only. The therapeutic effects of the two groups were analyzed.</p><p><b>RESULTS</b>After an 8-week treatment, the scores of self-feeling symptoms of SCL-90, SAS and SDS in Group A were 70.5 +/- 22.3, 18.7 +/- 8.5 and 21.4 +/- 9.0, respectively, significantly lower than those in Group B (P < 0.05) and the rates of efficacy and obvious efficacy in alleviating prostatodynia in Group A were 100% and 72.1%, respectively, both higher than in Group B (P < 0.05).</p><p><b>CONCLUSION</b>Molida therapy in the out-patient department is useful in improving the psychological disorder and enhancing the therapeutic effect for patients with III B prostatitis.</p>