Proteomic analysis reveals that Polygonatum cyrtonema Hua polysaccharide ameliorates mice muscle atrophy in chemotherapy-induced cachexia.

Polygonatum cyrtonema Hua polysaccharide (PCP) is the main bioactive compound derived from the herb Polygonati Rhizoma, known for its anti-fatigue, antioxidant, immunomodulatory, and anti-inflammatory properties. However, its effectiveness on alleviating chemotherapy-induced muscle atrophy has been unclear. In this study, we utilized proteomic analysis to investigate the effects and mechanisms of PCP on gemcitabine plus cisplatin (GC) induced muscle atrophy in mice. Quality control analysis revealed that the functional PCP, rich in glucose, is a heterogeneous polysaccharide comprised of nine monosaccharides. PCP (64 mg/kg) significantly alleviated body muscle, organ weight loss, and muscle fiber atrophy in chemotherapy-induced cachectic mice. Moreover, PCP suppressed the decrease in serum immunoglobulin levels and the increase in pro-inflammatory factor interleukin-6 (IL-6). Proteomic analysis demonstrated that PCP contributed to the homeostasis of protein metabolism in gastrocnemius muscle. Diacylglycerol kinase (DGKζ) and cathepsin L (CTSL) were identified as primary PCP targets. Furthermore, the IL-6/STAT3/CTSL and DGKζ/FoxO/Atrogin1 signaling pathways were validated. Our findings suggest that PCP exerts an anti-atrophy effect on chemotherapy-induced muscle atrophy by regulating the autophagy-lysosome and ubiquitin-proteasome systems.

Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome in a Chinese family: A case report and review of literature.

BACKGROUND: Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant genetic disease characterized by severe autoimmune inflammation, caused by mutations in the PSTPIP1 gene. Due to PAPA heterogeneous clinical manifestation, misdiagnosis or delayed diagnoses are difficult to avoid. With the use of whole-exome sequencing, we identified a missense mutation in the PSTPIP1 gene in a Chinese family. To the best of our knowledge, this is the first case of PAPA reported in China. CASE SUMMARY: A 9-year-old boy suffered from recurrent aseptic pyogenic arthritis triggered by minor trauma or few obvious predisposing causes for more than 3 years. Pyogenic arthritis occurred every 3-5 mo, affecting his knees, elbows, and ankle joints. Treatments, such as glucocorticoids, antibiotics, even surgeries could alleviate joints pain and swelling to some extent but could not inhibit the recurrence of arthritis. Similar symptoms were present in his younger brother but not in his parents. According to the whole-exome sequencing, a missense mutation in exon 11 of the PSTPIP1 gene (c.748G>C; p.E250Q) was detected in the boy, his younger brother and his father. Taking into account the similar phenotypic features with PAPA syndrome reported previously, we confirmed a diagnosis of PAPA syndrome for the family. CONCLUSION: In this case, a missense mutation (c.748G>C; p.E250Q) in PSTPIP1 gene was identified in a Chinese family with PAPA syndrome. Previous studies emphasize the fact that PAPA syndrome is hard to diagnose just through the clinical manifestations owing to its heterogeneous expression. Genetic testing is an effectual auxiliary diagnostic method, especially in the early stages of pyogenic arthritis. Only if we have a deep understanding and rich experience of this rare disease can we make a prompt diagnosis, develop the best clinical treatment plan, and give good fertility guidance.

Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.

[Research progress on anti-hyperuricemia effects and mechanisms of Chinese medicines based on regulation of intestinal flora and metabolites].

Chronical hyperuricemia, a severe metabolic disease characterized by increased serum uric acid, urea nitrogen, and creatinine, has a positive correlation with the risks of gouty arthritis, diabetes, hypertension, and kidney damage. Abnormal purine metabolism and reduced uric acid excretion are the major causes of hyperuricemia, which, thus, points to a potential strategy of preventing from or delaying the progress of hyperuricemia-related diseases and its complications by effectively controlling the serum uric acid level. Increasing evidence has revealed that Chinese medicines alleviate hyperuricemia through regulating intestinal flora, which plays a pivotal role in regulating metabolites, including uric acid level. The disease treatment with traditional Chinese medicine is based on syndrome differentiation, and Chinese medicines often have multiple effects and a wide range of targets. In this review, we summarized the anti-hyperuricemia effects and mechanisms of active compounds in Chinese medicines, single Chinese medicinal herbs, and Chinese medicinal prescriptions in regulating the uric acid level via intestinal flora and metabolites, which will be helpful for further study and application of Chinese medicines in hyperuricemia treatment.

[Investigation on operation timing of limb fractures combined with severe craniocerebral trauma in children].

OBJECTIVE: To investigate the best choice of operation opportunity and operation plan for limb fractures combined with severe craniocerebral trauma in children. METHODS: From January 2005 to July 2012,36 patients with limb fractures and severe craniocerebral trauma were received,including 24 males and 12 females aged from 1 to 13 years old (mean, 6.1 +/- 3.0). The time from injury to hospital was (18.0 +/- 15.0) h. Glasgow coma score were less than 8 with an average of 6.4 +/- 1.3. AIS-ISS score were 25.9 +/- 8.1. Thirteen patients were open fracture, 23 were closed fracture. Patients were divided into immediate operation group (21 patients) received fracture fixation with 24 h, the average time was (15.0 +/- 7.4) h, and delayed operation group (15 patients) received fracture fixation after 24 h, the average time was (165.4 +/- 114.6) h. All patients were treated by open reduction, and 33 cases by internal fixation, 3 cases were external fixation. Operative time, blood loss, fracture healing time and brain trauma,physical trauma, postoperative rehabilitation situation were observed and evaluated. RESULTS: All patients were healed at stage I ,and no dead, aggravating of coma, disorders of breathing and circulation occurred during operation. Operative time,blood loss,healing time in immediate operation group was (44.5 +/- 25.3) min, (47.1 +/- 36.5) ml, (2.7 +/- 0.5) months, respectively; while in delayed operation group was (87.0 +/- 40.0) min, (112.7 +/- 67.5) ml, (3.8 +/- 1.2) months,respectively; and there were obvious differences between two groups. There was no siginificant meaning in Glasgow coma score and Fugl-Meyer motor function between immediate operation group (4.7 +/- 0.6, 97.9 +/- 2.7) and delayed operation group (4.7 +/- 0.5, 97.7 +/- 3.9) (t = 0.23, P > 0.05; t = 0.11, P > 0.05). CONCLUSION: The condition of limb fractures combined with severe craniocerebral trauma in children is seriously, comfortable surgical opportunity should according to particular case, and immediate operation can performed on the condition of stabled vital signs.

[Clinical characteristics of pediatric victims in the Lushan and Wenchuan earthquakes and experience of medical rescue].

OBJECTIVE: To get a more comprehensive understanding of the clinical characteristics of pediatric victims in earthquake and to summarize the experience of medical rescue. METHODS: The clinical information was collected from the pediatric victims who were admitted to West China Hospital, Sichuan University following the Lushan earthquake in 2013 and Wenchuan earthquake in 2008. The clinical data were compared between the pediatric victims in the two earthquakes. RESULTS: Thirty-four children under 14 years of age, who were injured in the Lushan earthquake, were admitted to the West China Hospital before April 30, 2013. Compared with the data in the Wenchuan earthquake, the mean age of the pediatric victims in the Lushan earthquake was significantly lower (P<0.01), and the mean time from earthquake to hospitalization was significantly shorter (P<0.01). In the Lushan earthquake, 67.6% of the injured children had variable limb fractures; traumatic brain injury was found in 29.4% of hospitalized children, versus 9.5% in the Wenchuan earthquake (P<0.05). Among the 34 children, no amputation and death occurred, and all the 13 severe cases started to recover. CONCLUSIONS: There were higher proportions of severely injured children and children with traumatic brain injury in the Lushan earthquake than in the Wenchuan earthquake. But these cases recovered well, which was possibly due to timely on-site rescue and transfer and multi-sector, multi-institution, and multidisciplinary cooperation.

[Study on the expression of vitamin D receptor in bone of immature rats of disuse osteoporosis].

OBJECTIVE: To study the expression of vitamin D receptor in bone of immobilized immature rat and explore the relation between disuse osteoporosis (DOP) and the expression of vitamin D receptor (VDR) in bone. METHODS: Rats aging 4 weeks were immobilized by limb-tail fixation for 2 and 4 weeks respectively, and then the wet weight, gray weight, bone mineral density of femurs and tibiae were measured, the histopathological and histomorphological parameters also were detected, which were used to evaluate the effect of immobilization on bone content and bone structure of femurs and tibiae in growing rats. The VDR expression of femurs and tibiae in the growing rats was evaluated by immunohistochemistry and image analysis. RESULTS: The wet weight, gray weight, and bone mineral density of immobilized limbs in the growing rats were all lower than those in age-matched control groups (P < 0.05). There were rare, small and broken bone trabeculae found in the histological films of proximal tibial metaphysis of immobilized limbs, with decreased trabecular area and perimeter (P < 0.05), comparing with the age-macthed control groups. Over-expression of VDR in cellular plasma and nuclear membranes of osteoblasts was also found in the proximal metaphysis of right hind limb in immobilized growing rats. CONCLUSIONS: It is a definite method to establish animal model of DOP in young rats by leg-tail fixation; over-expression of Vitamin D receptors in growing bone of immobilized rat limbs means that the disorder of vittamin D endocrine system may be related to pathogenesis of DOP.

Anatomic study of the synovial folds of the occipito-atlanto-axial joints.

This study was performed to observe and measure synovial folds of the occipito-atlanto-axial joints and to explore their clinical significance. Two hundred ninety eight occipito-atlanto-axial joints from 30 embalmed cadavers of children and 20 of adults were dissected to find the incidence, quantity, distribution, forms, dimension, and histology of synovial folds. Synovial folds were found in most joints in both groups except for the posterior median atlantoaxial joints. Most of synovial folds were crescent-shaped, distributed on the superior aspects of the anterior median atlantoaxial joints, or in the antero-lateral aspects of the atlantooccipital joints and the lateral atlantoaxial joints. Compared to the adult group, the child group had a higher incidence of synovial folds (72.5% joints). The adult incidence was found to be 58.5%. 54.3% of the synovial folds in child were medium size or large size, but only 30.1% of the synovial folds in adult were medium size and there were no large ones. Microscopically, there were three histologic types synovial folds in these cervical joints, and 78.9% of them belonged to adipose type or fibro-adipose type in child, but only 45.8% belonged to the two types in adult. Our data suggest that the larger synovial folds in children may predispose them to an increased rate of entrapment with resultant edema and subluxation of the associated joint complex. This may be the cause why some cervical spine diseases preferentially take place in children rather than in adult, such as benign paroxysmal torticollis'atlantoaxial rotatory deformity and Grisel's syndrome.