Analysis of COL1A1 gene variation and clinical prevention and treatment in patients with Van der Hoeve syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinical phenotype, treatment and prevention of Van der Hoeve syndrome, and analyze the variation characteristics of its related gene COL1A1. Methods: Hearing and sequencing data of syndromic deafness patients who had undergone genetic testing for deafness at the Chinese People's Liberation Army General Hospital since January 2008 to October 2020 were retrospectively reviewed. The variation of the COL1A1 gene and return visits to traceable patients and families were summarized, the disease progress and clinical treatment effects were analyzed, and the prevention strategies were discussed. Results: A total of 7 patients with COL1A1 gene mutation underwent clinical intervention. The mutation sites were c.1342A>T (p.Lys448*), c.124C>T (p.Gln42*), c.249insG(p.Ala84*), c.668insC(p.Gly224*), c.2829+1G>C, c.1081C>T (p.Arg361*), c.1792C>T (p.Arg598*), of which c.1081C>T and c.1792C>T had been previously reported, and the remaining 5 were novo mutations that have not been reported. All the 7 probands underwent stapes implantation and received genetic counseling and prevention guidance. Conclusions: Van der Hoeve syndrome belongs to osteogenesis imperfecta type Ⅰ. The disease has high penetrance. Timely surgical intervention for hearing loss can improve the life quality in patients. Accurate genetic counseling and preimplantation genetic diagnosis can achieve the primary prevention for the disease.

Penicacids E-G, three new mycophenolic acid derivatives from the marine-derived fungus Penicillium parvum HDN17-478 / 中国天然药物

Three new mycophenolic acid derivatives, penicacids E-G (1-3), together with three known analogues, mycophenolic acid (4), 4'-hydroxy-mycophenolic acid (5) and mycophenolic methyl ester (6), were isolated from a marine-derived fungus Penicillium parvum HDN17-478 from a South China Sea marine sediment sample. The structures of compounds 1-3 were elucidated by HRMS, NMR, and Mosher's method. Among them, compounds 1 and 2 were the first examples of mycophenolic acid analogs with a double bond at C-3'/C-4' position. The cytotoxicity of 1-6 was evaluated against the HCT-116, BEL-7402, MGC-803, SH-SY5Y, HO-8910 and HL-60 cell lines, and compounds 4 and 6 showed potent cytotoxicity with IC

Selection and validation of internal reference genes for qPCR in Polygonatum cyrtonema tubers at different development stages and in response to abiotic stress / 中国中药杂志

In order to analyze the expression of genes involved in steroidal saponin biosynthesis pathway in Polygonatum cyrtonema tubers, it is very important to select internal reference genes that are stably expressed at different development stages and in response to abiotic stress. According to the previously established P. cyrtonema transcriptome database and reported internal reference genes in plant, this study systematically analyzed eight candidate internal reference genes including histone H2 A, glyceraldehyde-3-phosphate dehydrogenase, ACTIN, β-tubulin, ubiquitin-conjugating enzyme-E2-10, elongation factor 1-alpha isoform, 18 S rRNA and α-tubulin 4 for expression stability in P. cyrtonema tubers at different development stages and in response to methyl jasmonate(MeJA) stress by using Real time fluorescence quantitative PCR(qPCR). Based on the statistical analysis of qPCR results by using GeNorm, NormFinder and BestKeeper softwares, the expression of ubiquitin-conjugating enzyme-E2-10 and elongation factor 1-alpha isoform are the most stable in P. cyrtonema tubes at different development stages and in response to MeJA stress. The two internal reference genes were further validated by analyzing the expression of 4 genes involved in steroidal saponin biosynthesis pathways. In conclusion, ubiquitin-conjugating enzyme-E2-10 and elongation factor 1-alpha isoform can be used as the most appropriate internal reference genes for qPCR analysis in P. cyrtonema. This study also provide a foundation for future investigate the molecular mechanism of steroidal saponin biosynthesis pathways in P. cyrtonema.

Biotransformation and enzymatic mechanism of protoberberine alkaloids / 中国中药杂志

Protoberberine alkaloids belong to the quaternary ammonium isoquinoline alkaloids, and are the main active ingredients in traditional Chinese herbal medicines, like Coptis chinensis. They have been widely used to treat such diseases as gastroenteritis, intestinal infections, and conjunctivitis. Studies have shown that structural modification of the protoberberine alkaloids could produce derivative compounds with new pharmacological effects and biological activities, but the transformation mechanism is not clear yet. This article mainly summarizes the researches on the biotransformation and structure modification of protoberberine alkaloids mainly based on berberine, so as to provide background basis and new ideas for studies relating to the mechanism of protoberberine alkaloids and the pharmacological activity and application of new compounds.

Study of effect and mechanism of regulation of autophagy on epithelial-to-mesenchymal transition in idiopathic pulmonary fibrosis / 医学研究生学报

Objective The aim of this study was to explore the regulatory effects and mechanism of autophagy on epithelial-to-mesenchymal transition(EMT) in idiopathic pulmonary fibrosis(IPF). Methods The experiment was divided into two group: control group and experimental group(IPF group, autophagy induction group, autophagy inhibition group). A549 cells were cultivated by the conventional method in control group. The A549 cells of the experimental group were induced by TGF-β1(5 ng/mL). Then, no further treatment was given to IPF group. Rapamycin(10 μg/L) or 3-Methyladenine(10mmol/L) was given to autophagy induction group or autophagy inhibition group respectively. The hydroxyproline content of lung tissue was measured, and the mRNA and protein levels of α-SMA, LC3-Ⅱ or LC3-Ⅱ/LC3-Ⅰ, Beclin1, E-cadherin and Vimentin were tested by Realtime PCR and Western blot. Results At each time point, the hydroxyproline content of lung tissue and the mRNA and protein levels of α-SMA and Vimentin in the experimental group were significantly higher than those in the control group（all P<0.05）. The above detections in autophagy induction group or autophagy inhibition group were significantly lower or higher than those in the IPF group（all P<0.05）. The mRNA and protein levels of LC3-Ⅱor LC3-Ⅱ/LC3-Ⅰ, Beclin1 and E-cadherin in the experimental group were significantly lower than those in the control group（all P<0.05）. Moreover, the same detections in autophagy induction group or autophagy inhibition group were significantly higher or lower than those in the IPF group（all P<0.05）. Conclusion The autophagy and EMT played an important role in IPF. Induction of autophagy might inhibit the development of IPF by inhibiting EMT, and Inhibition of autophagy could promote the development of IPF by activating EMT.

Current status and future perspectives of daptomycin development / 药学学报

Due to the potent bactericidal activity and low incidence of drug resistance, the novel cyclic lipopeptide antibiotic - daptomycin has emerged as one of the first line antimicrobial agents in the treatment of serious infections caused by gram-positive resistant pathogens. This review summarizes the research advances of daptomycin in recent years, mainly including spectrum of antimicrobial activity, biosynthesis, mode of action, mechanism of drug resistance, structure-activity relationships, surotomycin and siderophore-daptomycin conjugate to kill multidrug resistant Acinetobacter baumannii. The findings summarized in this review highlight the directions of next-generation of daptomycin derivatives.

Novel antifungal agents against cryptococcal infections / 药学学报

Cryptococcal meningitis, caused by fungus Cryptococcus neoformans, is responsible for over a million infections and 600 000 deaths annually. Largely due to the limited treatment options and the intrinsic drawbacks coupled with drug resistance to current therapies, it is urgent to discover novel antifungal agents against cryptococcosis. An ideal antifungal drug should at least satisfy the following criteria: fungicidal, fungus-specific, permeable for the host barriers such as cell membranes of phagocytes and the blood-CNS barrier. Both discovery of candidates with novel mode of action and repurposing existing molecules with potent anti-cryptococcal activity are effective ways in discovery of new anti-cryptococcal agents. Here, we summarized recent advances in the study of anti-fungal activities, mechanisms of action, and clinical developments of new anti-cryptococcal drugs.

Novel liposomal drug delivery system actively targeting Cryptococcus neoformans and elimination of infection / 药学学报

The purpose of this study is to develop a liposomal drug delivery system actively targeting Cryptococcus neoformans and explore its feasibility in therapy of cryptococcal infection. The specific fungibinding peptide was screened from 12-mer random phage display library, and linked to PEG-DSPE as the functional material of liposomes. The targeting capability of peptide-modified liposomes were investigated by fungi binding assay in vitro and fluorescence imaging in vivo. Itraconazole as a model drug were then encapsulated in the liposomes and were evaluated in pharmacodynamic test in vitro and for therapeutic effects against cryptococcal meningitis complicated with pulmonary cryptococcosis in vivo. The results showed that the peptide (sequence:NNHREPPDHRTS) could selectively recognize Cryptococcus and effectively mediate the corresponding liposomal formulation to accumulate in the infection site in vivo. This peptide-modified liposome has a small particle size (mean diameter of 88.25±2.43 nm) with a homogeneous distribution and high encapsulation efficiency (88.05±0.25%) of itraconazole. After intravenous administration, the pathogens were obviously eliminated in lung and brain, and the life-span of model mice were significantly prolonged, suggesting a promising potential of this cryptococcosis targeting strategy.

Effect of aluminum phosphate gel and Kangfuxin on esophageal pathology and IL-8 and PGE2 expressions in a rat model of reflux esophagitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of aluminum phosphate gel and Kangfuxin on esophageal pathology and expressions of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in rats with reflux esophagitis and explore the possible mechanisms.</p><p><b>METHODS</b>Sixty SD rats were randomized into aluminum phosphate gel group (n=10), Kangfuxin group (n=10), aluminum phosphate gel+Kangfuxin group (n=10), model group (n=20), and control group (n=10). Except for those in the control group, all the rats were subjected to infusion of diluted lysolecithin with hydrochloric acid in the esophagus for 14 days. Ten rats in the model group and those in the control group were sacrificed to examine the pathological changes and contents of IL-8 and PGE2 in the esophagus using optical and electron microscopes and radioimmunoassay. The next day the rest rats were given corresponding treatments (saline in model group) administered into the esophagus on a daily basis for 14 days, after which esophageal pathologies and IL-8 and PGE2 contents were examined.</p><p><b>RESULTS</b>The model rats showed obvious esophageal pathologies including inflammatory cell infiltration, vacuolar degeneration of the epithelial cells, esophageal erosion and even ulceration, with severe detachment of the epithelial cells. The rats in all the intervention groups showed lessened esophageal pathologies and lowered esophageal IL-8 and PGE2 contents compared with those in the model group. Esophageal mucosal injury index and IL-8 and PGE2 contents were all significantly lower in rats receiving combined treatment with aluminum phosphate and Kangfuxin than in those receiving either of the treatments (P<0.05).</p><p><b>CONCLUSIONS</b>Both Kangfuxin and aluminum phosphate gel are effective in the treatment for reflux esophagitis induced by lysolecithin and hydrochloric acid, and their therapeutic effects are achieved possibly by reducing IL-8 and PGE2 levels in the esophagus.</p>

Treatment of depression fractures of posterolateral tibial plateau through a modified anterolateral approach / 中国骨伤

<p><b>OBJECTIVE</b>To study the therapeutic effects of posterolateral depression fractures of the tibial plateau through a modified anterolateral approach.</p><p><b>METHODS</b>From February 2011 to January 2012,13 patients with posterolateral depression fractures of the tibial plateau were treated through a modified anterolateral approach. There were 8 males and 5 females, ranging in age from 28 to 59 years old (49.2 years old on average). Data from patients were collected retrospectively as follows: X-ray, time of fracture healing and the complications of fracture healing. The patients were evaluated both clinically and radiologically according to the Rasmussen score system.</p><p><b>RESULTS</b>All the patients were followed up, and the duration ranged from 6 to 18 months (mean 13.7 months). All the patients got bony union. The average radiographic bony union time was 15.1 weeks (ranged, 11 to 17 weeks). No case of secondary articular depression was found. No complications such as malunion or joint stiffness were found. But 1 patient had superficial infection and 1 patient had common peroneal nerve injury. According to the Rasmussen score system,the mean radiological score was 16.50 ± 0.67 (ranged, 13 to 18), and the mean functional score was 25.20 ± 2.21 (ranged, 13 to 30). The mean range of knee motion was (125.3 ± 9.3)° (ranged, 0° to 135°).</p><p><b>CONCLUSION</b>Treatment of depression fractures of posterolateral tibial plateau with a modified anterolateral approach is a safe method with effective exposure, due to its stable fixation and relatively good outcome with minimal soft-tissue complications. It is regarded as an ideal procedure for depression fractures of posterolateral tibial plateau.</p>

Dendrobium officinale cliff epiphytic cultivation method / 中国中药杂志

To solve the issues of costly planting of facility cultivation method and inferior efficacy than wild herbs of Dendrobium officinale, the cliff epiphytic cultivation method was studied. To research the growth, agronomic traits, yield, polysaccharide and alcohol-soluble extract contents were measured on the D. officinale from different water regulation and cliff slope gradients treatments. The results showed that D. officinale epiphytic at 85 degrees-90 degrees cliff and sprayed water 1-2 h x d(-1) at the growing season can get better growth and obtain high yield, and the morphology has no different from wild cliff D. officinale, even in the environments without shade. The contents of polysaccharide and alcohol-soluble extract are closely related to the physiological ages, but significantly higher than the facility cultivation. It is possible that environmental stresses benefit the accumulation of polysaccharides, alcohol-soluble extract and other efficient ingredients.

Advances in studies on bear bile powder / 中国中药杂志

In this paper, a detailed analysis was made on relevant literatures about bear bile powder in terms of chemical component, pharmacological effect and clinical efficacy, indicating bear bile powder's significant pharmacological effects and clinical application in treating various diseases. Due to the complex composition, bear bile powder is relatively toxic. Therefore, efforts shall be made to study bear bile powder's pharmacological effects, clinical application, chemical composition and toxic side-effects, with the aim to provide a scientific basis for widespread reasonable clinical application of bear bile powder.

Research of Chinese herbal compound on promoting HIV immune reconstitution / 中国中药杂志

This article reviews the research reports of Chinese herbal compound on AIDS immune reconstitution for nearly 20 years, found that Chinese herbal compound has exact clinical efficacy for AIDS immune reconstitution. Therefore, we should give full play to the unique advantages of Chinese herbal compound in improving immunity, thus improving symptoms and improve quality of life, to achieve optimal clinical treatment of AIDS.

Research progress of Chinese medicine treatment of HAART-related toxic and side effect / 中国中药杂志

Highly active antiretroviral therapy (HAART) have made great progress in rapid inhibition of HIV, reduce the morbidity and mortality, etc; while it exists many limits, such as viruses rebound after discontinuation of drug, side effects, drug-resistant. With the emergence of these problems, researchers explored therapies by traditional Chinese medicine, so as to achieve target of lower antiviral drug side effect, raising antiviral treatment adherence. Through a large number of clinical tests, we achieved encouraging effects in treating HAART related side effects by Chinese medicine.

Research development of HIV drug resistance / 中国中药杂志

Highly active antiretroviral combination therapy significantly reduced the mortality, but in the high-speed copying, high genetic variation and drug selection pressure under the effect of the increasingly serious problem of drug resistance greatly weakened the role of HAART inhibit viral replication and reduce antiviral treatment. This paper reports the latest trends in HIV drug-resistance in order to develop anti-HIV drugs in clinical programs, research and development of new guidance anti-HIV-1 strategy to bring guidance.

Combined corpectomy in the treatment of multilevel cervical spondylotic myelopathy and ossified posterior longitudinal ligament / 中华骨科杂志

Objective To evaluate effect of combined corpeetomy for multilevel cervical spondylotic myelopathy (CSM) and ossified posterior longitudinal ligament (OPLL).Methods Fifteen patients with CSM or OPLL,including 9 males and 6 females,were treated with combined corpectomy which is characterized by C4 and C6 corpectomy,excision of osteophyma,protruded disc and/or ossified posterior longitudinal ligament on basis of preservation of C5 vertebral body,structural bone grafting in C3-5 and C5-7,and anterior cervical plate fixation at C3,C5,and C7.The clinical results were evaluated with Japanese Orthopaedic Association (JOA) score.X-rays and CT scans were taken to evaluate vertebral fusion,and MRI was used to access spinal canal decompression and condition of spinal cord.Results All patients were followed up for 9 to 42 months (average,26.7 months).Bony fusion was achieved in all 15 patients.The JOA score improved from preoperative 13.44±2.81 to postoperative 16.16±2.19 (P=0.0354).The cervical lordosis improved from preoperative 1.16°±11.74° to immediately postoperative 14.36°±7.85° (P=0.00217),and 12.92°+6.17° at the final follow-up (P=0.00292).The complications included temporary hoarseness in 2 cases,dysphagia in 1 case.Conclusion The combined corpectomy for treating CSM and OPLL can obtain reliable and satisfactory results.In operation,the preservation of C5 vertebral body can provide an additional screw anchoring force and strengthen stahility.

Novel inhibitors against the bacterial signal peptidase I / 药学学报

New antibiotics with novel modes of action and structures are urgently needed to combat the emergence of multidrug-resistant bacteria. Bacterial signal peptidase I (SPase I) is an indispensable enzyme responsible for cleaving the signal peptide of preprotein to release the matured proteins. Increasing evidence suggests that SPase I plays a crucial role in bacterial pathogenesis by regulating the excretion of a variety of virulent factors, maturation of quorum sensing factor and the intrinsic resistance against beta-lactams. Recently, breakthrough has been achieved in the understanding of three-dimensional structure of SPase I as well as the mechanism of enzyme-inhibitors interaction. Three families of inhibitors are identified, i.e. signal peptide derivatives, beta-lactams and arylomycins. In this article, we summarize the recent advance in the study of structure, activity and structure-activity relationship of SPase I inhibitors.

Antitumor effect of sphingosine kinase 1 inhibitor in combination with chemotherapy on SGC7901 gastric cancer cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of the sphingosine kinase 1 (SphK1) inhibitor N,N-dimethylsphingosine (DMS) in combination with chemotherapeutic drugs (DDP, 5-Fu, MMC) on the proliferation of gastric cancer cells (SGC7901) in vitro, and to evaluate whether SphK1 inhibitors could be used as synergetic agents in chemotherapy.</p><p><b>METHODS</b>SGC7901 cells were incubated in vitro with DMS (1 micromol/L) and 5-Fu, DDP, MMC at different concentrations in combination or separately for 24 h. The effects on the growth and survival of SGC7901 cells were determined by MTT assay. The inhibition rates were assessed by response surface analysis and the interactive relationships between the combined drugs were evaluated on the basis of positive/negative values of the cross product coefficients in the response surface equation.</p><p><b>RESULTS</b>The growth inhibition rate of the gastric cancer cells by treatment with DMS (1 micromol/L) was (10.23 +/- 0.74)%. The growth inhibition rates of the gastric cancer cells treated with 5-Fu (1, 5 and 25 microg/ml) for 24 h were (9.95 +/- 3.24)%, (21.04 +/- 2.19)%, and (45.49 +/- 3.60)%, respectively. The growth inhibition rates of the gastric cancer cells treated with DDP (0.5, 2.5 and 12.5 microg/ml) for 24 h were (9.38 +/- 0.79)%, (19.61 +/- 0.90)%, and (29.83 +/- 0.54)%, respectively. The growth inhibition rates of the gastric cancer cells treated with MMC (0.1, 0.5 and 2.5 microg/ml) for 24 h were (15.35 +/- 0.77)%, (24.72 +/- 0.83)%, and (30.68 +/- 0.28)%, respectively. There were significant differences among the inhibition rates caused by different concentrations of the drugs (P < 0.05). When 1 micromol/L DMS was used in combination with 5-Fu (1, 5, and 25 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (16.76 +/- 0.41)%, (27.28 +/- 0.29)% and (52.56 +/- 3.60)%, respectively. When 1 micromol/L DMS was used in combination with DDP (0.5, 2.5, and 12.5 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (15.35 +/- 0.86)%, (25.57 +/- 0.27)%, (36.37 +/- 0.51)%, respectively. When 1 micromol/L DMS was used in combination with MMC (0.1, 0.5, and 2.5 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (21.02 +/- 0.28)%, (32.10 +/- 0.27)%, (36.36 +/- 0.28)%, respectively. There were also significant differences among the growth inhibition rates caused by different concentrations of the drugs alone and in combination groups (P < 0.05).</p><p><b>CONCLUSIONS</b>DMS can suppress the proliferation of SGC7901 cells in vitro, and there are evident synergetic effects when it is used in combination with chemotherapeutic drugs. The results of this study indicate that SphK1 inhibitors may become novel and promising chemotherapeutic sensitizers.</p>

Characteristics of bone tunnel changes after anterior cruciate ligament reconstruction using Ligament Advanced Reinforcement System artificial ligament / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are different materials used for anterior cruciate ligament (ACL) reconstruction. It has been reported that both autologous grafts and allografts used in ACL reconstruction can cause bone tunnel enlargement. This study aimed to observe the characteristics of bone tunnel changes and possible causative factors following ACL reconstruction using Ligament Advanced Reinforcement System (LARS) artificial ligament.</p><p><b>METHODS</b>Forty-three patients underwent ACL reconstruction using LARS artificial ligament and were followed up for 3 years. X-ray and CT examinations were performed at 1, 3, 6, 12, 24, and 36 months after surgery, to measure the width of tibial and femoral tunnels. Knee function was evaluated according to the Lysholm scoring system. The anterior and posterior stability of the knee was measured using the KT-1000 arthrometer.</p><p><b>RESULTS</b>According to the Peyrache grading method, grade 1 femoral bone tunnel enlargement was observed in three cases six months after surgery. No grade 2 or grade 3 bone tunnel enlargement was found. The bone tunnel enlargement in the three cases was close to the articular surface with an average tunnel enlargement of (2.5 ± 0.3) mm. Forty cases were evaluated as grade 0. The average tibial and femoral tunnel enlargements at the last follow-up were (0.8 ± 0.3) and (1.1 ± 0.3) mm, respectively. There was no statistically significant difference in bone tunnel width changes at different time points (P > 0.05). X-ray and CT measurements were consistent.</p><p><b>CONCLUSIONS</b>There was no marked bone tunnel enlargement immediately following ACL reconstruction using LARS artificial ligament. Such enlargement may, however, result from varying grafting factors involving the LARS artificial ligament or from different fixation methods.</p>

Effects of cervical vertebrae degeneration on traumatic cervical cord injury / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the effects of cervical vertebrae degeneration on traumatic cervical cord injury.</p><p><b>METHODS</b>From January 2009 to December 2010, 24 patients with cervical cord injury without obvious fractures and dislocations were treated with operation, and their data were retrospectively analyzed. Among them, 16 males and 8 females, aged from 46 to 70 years old with an average of 59.1 years. Patients were divided into light degeneration group (6 cases), moderate degeneration group (10 cases) and severe degeneration group (8 cases), according to the preoperative degenerative degree of cervical vertebrae. Preoperative neurological dysfunction and postoperative neurological recovery were compared according to the JOA scores of Japanese Orthopaedic Society; quality of life were evaluated according to SF-36 scale (36-item Short Form Health Survey, SF-36).</p><p><b>RESULTS</b>All patients were followed up from 4 to 16 months with an average of 12 months. The JOA score of light, moderate, severe degeneration group were 12.1 +/- 1.5, 10.3 +/- 1.8, 7.3 +/- 1.0, respectively; and were respectively increased to 16.3 +/- 1.0, 15.3 +/- 1.4, 13.0 +/- 2.3 at the 3 months after operation. Postoperative JOA score showed the improvement rate of mid-long-term neurological level was light degeneration group (89.8%) > moderate degeneration group (76.6%) > severe degeneration group (58.8%). The results of preoperative SF-36 scale showed light degeneration group > moderate degeneration group > severe degeneration group; there was significant difference in comparison of two groups (P < 0.05 ).</p><p><b>CONCLUSION</b>Cervical degeneration is an important pathologic basis and risk factor in traumatic cervical cord injury, and the degenerative degree will directly influence the injury degree and prognosis of neurological function, the clinical relationship between them should be sufficiently paid attention to.</p>