Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.
Humans ; Male ; Adult ; Female ; Xanthomatosis, Cerebrotendinous/pathology* ; Pedigree ; Cholestanetriol 26-Monooxygenase/genetics* ; Mutation ; Ataxia

OBJECTIVE: To explore the clinical therapeutic effect of light and heat of moxibustion for knee osteoarthritis (KOA). METHODS: A total of 216 patients with KOA were randomized into a traditional moxibustion group (72 cases, 8 cases dropped off), a moxibustion light group (72 cases, 9 cases dropped off) and a moxibustion heat group (72 cases, 10 cases dropped off).The special light-heat separation moxibustion cup was applied, the patients in the traditional moxibustion group received the treatment of moxibustion, the patients in the moxibustion light group received the treatment of moxibustion light and the patients in the moxibustion heat group received the treatment of moxibustion heat. The acupoint selection of the three groups was Neixiyan (EX-LE 4), Dubi (ST 35) and Zusanli (ST 36), the treatment was given 20 min each time, 3 times a week, 4 weeks were required totally, and the follow-up surveys were made 4 and 8 weeks after treatment. The scores of Western Ontario and McMaster University osteoarthritis index (WOMAC) and visual analogue scale (VAS) were observed before treatment, after 2 and 4 weeks of treatment, 4 and 8 weeks after treatment. The therapeutic effects were evaluated according to the criterion of patient global assessment (PGA) after 4 weeks of treatment and 8 weeks after treatment. RESULTS: Compared with before treatment, the pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced after 2, 4 weeks of treatment and 4 weeks after treatment in the three groups (<0.05). The pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced 8 weeks after treatment in the traditional moxibustion group and the moxibustion heat group (<0.05). The stiffness score, physical function score and total score of WOMAC were reduced 8 weeks after treatment in the moxibustion light group (<0.05). The pain score, physical function score and total score of WOMAC in the traditional moxibustion group after 4 weeks of treatment were lower than the moxibustion light group (<0.05). Compared with before treatment, the VAS scores were reduced after 2, 4 weeks of treatment and 4 , 8 weeks after treatment in the three groups (<0.05). The improvement rates in the traditional moxibustion group and the moxibustion heat group after 4 weeks of treatment and 8 weeks after treatment were superior to the moxibustion light group (<0.05). CONCLUSION The light and heat of moxibustion have therapeutic effect for KOA, and the therapeutic effect of moxibustion heat is superior to moxibustion light.
Acupuncture Points ; Hot Temperature ; Humans ; Light ; Moxibustion ; Osteoarthritis, Knee ; therapy ; Treatment Outcome

Objective To observe the efficacy difference between different needling manipulations in treating acute stroke with point-toward-point needling at scalp acupoints, for seeking the optimal treatment protocol. Method Ninety patients with acute stroke were randomized into a manual needling group, an electroacupuncture group, and a needle-retaining group, 30 cases each. In addition to the neurological treatment, the three groups were all given point-toward-point needling from Baihui (GV20) to Taiyang (EX-HN5) on the affected side, respectively with manual twisting, electroacupuncture and needle retaining methods. Before and after 14-day treatment, the Neurological Deficit Score (NDS), level of neuron specific enolase (NSE) and total efficacy were compared among the three groups. Result The NDS dropped significantly in the three groups after the intervention (P<0.05); the manual needling group showed the most significant improvement, better than the electroacupuncture group and needle retaining group. The level of NSE declined significantly in the three groups after the intervention (P<0.05); the decrease in the manual needling group was the most significant compared to that in the electroacupuncture group and needle retaining group. The total effective rate in the manual needling group (90.0%) was significantly higher than that in the electroacupuncture group and needle retaining group (P<0.05). Conclusion Point-toward-point needling at scalp acupoints with manual operation can effectively improve the neurological deficit in stroke patients, and the application of needling manipulations can further enhance the therapeutic efficacy, which is specific.

OBJECTIVETo investigate the mechanism by which heat shock protein 90 (HSP90) regulates 26S proteasome in hyperthermia.

METHODSHyperthermic HepG2 cell models established by exposure of the cells to 42 degrees celsius; for 3, 6, 12, and 24 h were examined for production of reactive oxygen species (ROS) and cell proliferation, and the changes in Hsp90α and 26S proteasome were analyzed.

RESULTSROS production in the cells increased significantly after hyperthermia (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated Hsp90α but decreased the expression level (F=164.174, P<0.001) and activity (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small interfering RNA targeting Hsp90α also showed significantly decreased expression of 26S proteasome (F=180.231, P<0.001).

CONCLUSIONThe intracellular ROS production increases as the hyperthermia time extends. Heat stress and ROS together cause protein denature, leading to increased HSP90 consumption and further to HSP90 deficiency for maintaining 26S proteasome assembly and stability. The accumulation of denatured protein causes unfolded protein reaction in the cells to eventually result in cell death.

HSP90 Heat-Shock Proteins ; metabolism ; Hep G2 Cells ; Hot Temperature ; Humans ; Proteasome Endopeptidase Complex ; metabolism ; RNA, Small Interfering ; genetics ; Reactive Oxygen Species ; metabolism ; Up-Regulation

Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa (GS) and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS (GS group, n=8) or intrahepatic via portal vein (PV group, n=5). Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation (mean survival time, 7.16±0.69 days). However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group (mean survival time, 120±28.58 days; P<0.01 vs. GS group). The results of intravenous glucose tolerance test (IVGTT) confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles.
Animals ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; therapy ; Dogs ; Gastric Mucosa ; metabolism ; transplantation ; Glucose ; metabolism ; Glucose Tolerance Test ; Graft Survival ; Humans ; Insulin ; metabolism ; Islets of Langerhans Transplantation ; Liver ; pathology ; Liver Transplantation ; Transplantation, Autologous

OBJECTIVETo investigate whether apollon immunoexpression in breast cancer tissues helps to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC).

METHODSThe expressions of Apollon, Her-2, estrogen receptor (ER) and progesterone receptor (PR) were detected immunohistochemically in biopsy tissues from 124 breast cancer patients. The clinical responses to NAC were evaluated in line with the response evaluation criteria in solid tumors (RECIST). The pCR rate was analyzed for different types of breast cancer. The correlations between Apollon status with Her-2, ER, PR, lymph node status and tumor size were analyzed. Immunohistochemistry was used to compared the changes in Apollon expression in the breast cancer tissues before and after NAC.

RESULTSThe pCR rate was 18.5% (23/124) in these patients. Negative expressions of apollon, ER and PR were all associated with a higher pCR rate after NAC. Apollon was significantly correlated with Her-2, ER, PR and lymph node involvement. Chemotherapy significantly down-regulated apollon expression in the tumor cells.

CONCLUSIONA negative apollon expression might be a predictor of pCR in patients with breast cancer.

Biopsy ; Breast Neoplasms ; drug therapy ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; metabolism ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

Adult ; Angiofibroma ; chemistry ; pathology ; Giant Cell Tumors ; chemistry ; pathology ; Humans ; Laryngeal Neoplasms ; chemistry ; pathology ; Male ; Middle Aged ; Vocal Cords

Objective To investigate the effect of excessive fluoride,aluminum on Zn,Fe,Ca,Mg,Cuin rat blood.Methods Forty eight SD rats were randomly divided into 4 groups matched with their weights:control group,high aluminum group,high fluorine group and high fluorine-aluminum group.Aluminum content in their drinking water was 0,90,0,90 mg/L respectively.Fluorine content of their feed was 5.2,5.2,106.0,106.0 mg/kg and aluminum Was 6.8,6.8,19.7,19.7 mg/kg respectively.90 days later,the level of blood Zn,Fe,Ca,Mg, Cu Was detected by the atomic absorption spectrometry.Results Compared among these groups,Zn,Fe,Mg and Cu content of the whole blood had significant difierences(F=46.25,14.74,6.10,2.93,P<0.05),while Ca content of the whole blood did not significantly change(F=2.81.P>0.05).Factorial analysis showed that excessive intake of aluminum could significantly decreased Zn,Fe,Mg content of the blood(F=42.66,5.41,7.04,P<0.05)and excessive intake of fluorine could significantly decreased Zn,Fe,Mg,Cu content of the blood(F=64.50,37.90,9.75,6.74, P<0.05).The coexistence offluorine and Muminum had interaction to the level of Zn(F=31.59,P<0.05)and did not obviously interact with other elements(F=0.91,1.63,1.51.0.00,P>0.05).Compared with the control group [(131.30 ±13.86)μmol/L,(10.24 ±1.02),(1.71 ±0.19)mmol/L,(20.43 ±4.42)μmol/L],Zn content in the high aluminum group[(90.84±9.98)μmol/L]decreased significantly(P<0.05),so did Zn,Fe,Mg content in tlle high fluorine group[(85.85 ±10.92)μmol/L,(8.49 ±0.68),(1.52 ±0.13)mmol/L],the difference being statistically significant(P<0.05)0Zn,Fe,Mg,Cu content in the high fluorine-aluminum group,being(82.82 ±11.00)μmol/L, (8.16±0.45),(1.46±0.09)mmoL/L,(15.69±2.38)μmol/L,respectively,all decreased signitlcarIdy(P<0.05). Compared with the high aluminum group[(9.43±1.09)mmol/L],Fe content of the high fluorine aluminum group[(8.16±0.45)mmol/L]decreased significantly(P<0.05).Conclusions Excessive fluoride can cause blood zn, Fe,Mg,Cu decline,so can excessive aluminum.Combination of excessive fluofine and aiuminum has 8ignificant synergic effect on the level of Zn but have rio influence on Ca.

AIMTo explore the intestinal absorption characteristics of lumbrokinase (YJM-I) in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption.

METHODSThe absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo.

RESULTSYJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1% SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5% SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD.

CONCLUSIONThe results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.

Administration, Oral ; Animals ; Area Under Curve ; Caprylates ; pharmacology ; Chitosan ; pharmacology ; Deoxycholic Acid ; pharmacology ; Duodenum ; drug effects ; metabolism ; Edetic Acid ; pharmacology ; Endopeptidases ; administration & dosage ; pharmacokinetics ; Injections, Intravenous ; Intestinal Absorption ; Male ; Metabolic Clearance Rate ; Poloxamer ; pharmacology ; Rats ; Rats, Sprague-Dawley

Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Heart Failure ; drug therapy ; physiopathology ; Hemodynamics ; Male ; Myocardial Ischemia ; drug therapy ; physiopathology ; Phytotherapy ; Rats ; Rats, Wistar ; Rhodiola