Off-label use means that the intended use of the drug is not included in the instructions approved by the National Medical Products Administration,including unapproved indication,dosage,the course of treatment,route of administration,or population.The formulation of Pharmaceutical Supply Services-Key Medications Management-Off-label Uses is based on relevant laws,regulations,normative documents,guidelines,literatures,and expert opinions,and follows the principles of scientificity,versatility,instructiveness,and operability.This standard regulates and standardizes the institutional and organizational construction,process management,and the whole process of quality management and evaluation improvement of off-label uses,which is the basis for medical institutions to carry out off-label uses management.This article introduced the formulation process of the off-label uses standard and analyzed the key contents of the standard,which would help medical institutions to better comply with and meet the requirements of this standard in the practice of off-label use management.

Objective: To examine the effect of posterior atlanto-axial intraarticular distraction technique as revision surgery for failed posterior fossa decompression in patients with basilar invagination(BI) and atlanto-axial dislocation(AAD). Methods: The clinical data of 13 cases of AAD accompanied with BI treated at Department of Neurosurgery, Xuanwu Hospital, Capital Medical University were retrospectively analyzed. There were 3 males and 10 females,aged (42.6±9.5) years (range:30 to 63 years). All cases had assimilation of atlas and once underwent posterior fossa decompression. Anterior tissue was released through posterior approach followed by cage implantation into facet joint and occipital-cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line(DCL),clivus-canal angle(CCA) and the length of syrinx were collected. Paired sample t test was used to compared the data before and after operation. Results: All patients underwent surgery successfully, the mean surgical time was (187.7±47.4) minutes (range from 116 to 261 minutes). Twenty occipital condyle screws, 26 C2 pedicle screws and 3 occipital plates were implanted. Clinical symptoms improved in all patients. Twelve patients had complete reduction of basilar invagination and atlanto-axial dislocation, 1 achieved near completely reduction of basilar invagination. The postoperative ADI, DCL and CCA significantly improved((4.3±1.1) mm vs. (1.8±0.8) mm, (11.7±5.0) mm vs. (6.4±2.8) mm, (142.4±7.9)° vs. (133.3±7.9)°, all P<0.01).There were 5 cases with syringomyelia before surgery, and shrinkage of syrinx was observed 1 week after surgery in all cases. Eight patients achieved bone fusion 3 months after surgery, all patients achieved bone fusion 6 months after surgery. The JOA score increased from 12.8±2.3 before surgery to 14.8±1.3 one year after surgery, with statistically significant difference (t=4.416, P<0.01).No implant failure, spacer subsidence and infection were observed. Conclusion: In cases of failure posterior fossa decompression of basilar invagination and atlanto-axial dislocation, using posterior atlanto-axial intraarticular distraction and cantilever technique with cage implantation could achieve complete reduction and symptomatic relief.
Atlanto-Axial Joint/surgery* ; Female ; Humans ; Joint Dislocations/surgery* ; Male ; Pedicle Screws ; Platybasia/surgery* ; Reoperation ; Retrospective Studies ; Spinal Fusion/methods*

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l

Objective To investigate the expression of semaphorin 3A (Sema3A) and its receptor neuropilin-1 (NRP-1) in gastric cancer and its correlation with microvessel density (MVD), and then to explore the effect of recombinant human Sema3A on angiogenesis of gastric cancer and the associated mechanisms. Methods Forty cases of gastric cancer tissues and its corresponding adjacent normal tissues were used to detecte the expression of Sema3A, NRP-1 and MVD in tissues by immunohistochemistry method . The expression level of Sema3A in serum of gastric cancer patient group and normal control group were measured by Enzyme-linked immuno-sorbent assay (ELISA). Western blotting was used to detect the expression of Sema3A and NRP-1 in five gastric cancer cell lines (MGC-803,HGC-27,MKN-28,SGC-7901,MKN-45) and human gastric mucosal epithelial cell (GES-1). Transwell chamber was used to construct non-contact in vitro co-culture system, in which the effects of different concentrations of recombinant human Sema3A on angiogenesis in gastric cancer were analyzed by tube formation assay preliminarily. The expression levels of vascular endothelial growth factor receptor 2 (VEGFR2) and NRP-1 in co-culture system were detected by Western blotting. Results The expression levels of Sema3A in gastric cancer tissues, cell lines and patient serum were significantly lower than that in the control group(P<0. 05), while the expression of NRP-1 in gastric cancer tissues and MKN-28 cells was significantly increased, and both of them were associated with TNM staging of gastric cancer (P < 0. 05) . In vitro co-culture system, The tube forming abilities of human umbilical vein endothelial cell (HUVEC) were decreased in recombinant human Sema3A treated group, and this phenomenon was concentration dependent. The expression of VEGFR2 protein was down-regulated by recombinant human Sema3A. Conclusion The expression of Sema3A was decreased in gastric cancer tissues, cell lines and patient serum, and negatively correlated with microvessel density. The recombinant human Sema3A could inhibit the angiogenesis of gastric cancer in vitro, which may be related to down-regulation of VEGFR2 protein expression.

BACKGROUND: It remains poorly understood whether anterior column quadrilateral wing plate exists to solve intraoperative multiple plastic and quadrilateral in vivo shift for treating acetabular anterior column and acetabular quadrilateral body fractures.OBJECTIVE: To figure out the promising application on measurement of anatomical character parameters when designing acetabular anterior column and acetabular quadrilateral body using Mimics software. METHODS: 60 pelvic CT scan data were collected and three-dimensionally reconstructed by Mimics software. The following anatomical character parameters were measured, including the angle between plane of arcuate line of true pelvis and plane of quadrilateral surface, the four boundary lines of quadrilateral body, and the thickness of substance of bone in quadrilateral region. The projection curve on quadrilateral surface of acetabular margin and dangerous zone for screw placement were both drew. Above all, the study attempted to find out the proper safe entry point of quadrilateral screw and to measure their leaning inside angles.RESULTS AND CONCLUSION: (1) The angle between plane of arcuate line of true pelvis and plane of quadrilateral surface was not significantly different between males and females. (2) The minimum thickness of quadrilateral body in males was larger than that in females. (3) The maximum leaning angle flapper plate screw P1 and P2 for quadrilateral body was significantly smaller in males than in females, but that of screw P3 was not significantly different between males and females. (4) The application of Mimics software made it easier, more intuitive and more practical for the design or development of new plate for acetabular anterior column and acetabular quadrilateral body. The common points and difference between acetabular anterior column and acetabular quadrilateral body could be specifically described by the new anatomical character parameters, which are defined by bone surface features of pelvis.

Objective:To investigate the dynamic change of left ventricular systolic synchrony in patients with atrial septal defect (ASD) before and after interventional occlusion using real-time three-dimensional echocardiography (RT-3DE).Methods:A total of 52 patients undergoing interventional occlusion in Zhongshan Hospital from September 2015 to January 2016 were enrolled in this study.All subjects were assigned to take RT-3DE one day before,one day and one month after the interventional occlusion.TomTec 4D LV-Analysis CRT 1.0 software was used to analyze volume-time curves (VTC) of the 16 segments of the left ventricle.Parameters including time to minimal segmental volume (Tmsv),time to minimal segmental volume-standard deviation (Tmsv16-SD),and time to minimal segmental volume-difference (Tmsv16-Dif) were analysed.These three parameters were standardized by dividing cardiac cycle to generate other three parameters:Tmsv％,Tmsv16 SD％,and Tmsv16-Dif％.Results:VTC before the interventional occlusion suggested dyssynchronation of the left ventricular systole;VTC of one day after the interventional occlusion suggested synchronization of the left ventricle.So did the results of one month after the interventional occlusion.Accordingly,parameters including Tmsv,Tmsv％,Tmsv16 SD,Tmsv16-SD％,Tmsv16-Dif,and Tmsv16-Dif％ were significantly improved one day after occlusion as compared with one day before occlusion.These parameters were not significantly changed one month after occlusion as compared with one day after occlusion.In terms of the contraction amplitude,only a few segments showed a significant improvement one day after the interventional occlusion,most segments did not improve until one month later.Conclusions:Interventional occlusion significantly improved left ventricular systolic synchronization in patients with ASD one day after occlusion.Additionally,the contraction amplitude was significantly improved one month after the interventional occlusion.

OBJECTIVETo investigate the efficacy and safety of sphincter-preserving procedure with transabdominal intersphincteric resection for ultra-low rectal cancer.

METHODSClinical data of 61 cases with ultra-low rectal cancer (distance from anal verge ranged from 4-5 cm) were analyzed retrospectively. The patients underwent sphincter-preserving procedure with intersphincteric resection and telescopic anastomosis.

RESULTSThere were 34 males and 27 females. The mean age was 56.7 years. The inferior border of the tumor was 4 cm above the anal verge in 21 cases, and 5 cm in 40 cases. There 55 patients with rectal adenocarcinoma in this cohort. The tumor was well-differentiated in 24 cases, moderately-differentiated in 29 cases, and poorly-differentiated in 2 cases. There were 6 cases with malignant adenoma. The TNM staging was T1N0M0 in 36 cases, T2N0M0 in 23, and T3N1M0 in 2. The ability to control defecation significantly improved in 1-3 months postoperatively, and returned to normal in 6-12 months. Two patients developed anastomotic leak (3.3%), and 3 anastomotic stenosis (4.9%) postoperatively. Fifty-four patients(88.5%) had follow-up. The median follow-up time was 6.2 years. The local recurrence rate was 5.6%, and the 5-year-survival rate was 73.5%.

CONCLUSIONSphincter-preserving procedure with intersphincteric resection and telescopic anastomosis is a safe and effective procedure for ultra-low rectal cancer.

Adult ; Aged ; Aged, 80 and over ; Anal Canal ; pathology ; surgery ; Anastomosis, Surgical ; methods ; Female ; Humans ; Male ; Middle Aged ; Rectal Neoplasms ; pathology ; surgery ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To explore the effect of ketamine on adrenal pheochromocytoma (PC12) cell proliferation inhibition and induction of apoptosis and its mechanism. METHODS: PC12 cells of rats were models for dopaminergic neuron. PC12 cells were cultured with ketamine at concentrations of 0.9, 1.2, 1.5, 1.8 and 2.1 mmol/L, respectively. The cell viability was measured by MTT method after incubation at 12, 24, 48 and 72h. Hoechst stain was used to observe the morphological changes of apoptosis. PC12 cells cultured after 48 h with different concentrations of ketamine were selected to detect apoptotic rate using flow cytometry and detect the expression of bax and bcl-2 proteins using Western blotting. RESULTS: For different concentrations of ketamine, vitality of PC12 cells significantly decreased with increase of the incubation time. Apoptosis was obviously observed using Hoechst staining. Flow cytometry showed that apoptosis rates significantly increased with increasing ketamine concentrations. CONCLUSION Ketamine can inhibit the proliferation of PC12 cell by inducing apoptosis of the PC12 cell in a concentrations-dependent manner. The underlying mechanism may be related to promoting the expression of bax and inhibiting the expression of bcl-2 in the cells.
Anesthetics, Dissociative/pharmacology* ; Animals ; Apoptosis/drug effects* ; Blotting, Western ; Cell Proliferation/drug effects* ; Dose-Response Relationship, Drug ; Flow Cytometry ; Gene Expression Regulation/drug effects* ; Ketamine/pharmacology* ; PC12 Cells ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Time Factors ; bcl-2-Associated X Protein/metabolism*

OBJECTIVETo evaluate the clinical efficacy, feasibility and safety of sphincter-preservation with telescopic anastomosis of colon and rectal mucosa in low-middle rectal cancer.

METHODSA retrospective analysis was carried out in 371 patients with low-middle rectal cancer in whom telescopic anastomosis was used. There were 224 males and 147 females, with a mean age of 57.9 (21-99) years. The lower margins of the tumors located between 5-8 cm from the anal verge. On histopathology, there were 361 adenocarcinomas, including 138 well-differentiated, 201 moderately differentiated, 11 poorly differentiated, 11 mucinous adenocarcinoma, and 10 adenomas with neoplastic changes. According to the Duke's stage classification, 120 were TNM stage I, 222 stage II, 26 stage III, and 3 stage IV.

RESULTSThree hundred and eighteen (318/371, 85.7%) cases were followed up, and the median follow up time was 5.8 years. Postoperative complications were observed, including 16(4.3%) cases with anastomotic leak, and 8 (2.1%) with anastomotic stenosis. All the patients resumed normal bowel function during 12-24 weeks after operation, with 1-3 times per day. The local recurrence rate was 6.3% (20/318). Hepatic and lung metastasis was 14.5% (46/318) and 2.5% (8/318), respectively. The 5-year survival rate was 69.7%.

CONCLUSIONThe sphincter-preservation with telescopic anastomosis procedure is safe and effective for low-middle rectal cancer, and the sphincter function can be well-preserved.

Adenocarcinoma ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Anal Canal ; surgery ; Anastomosis, Surgical ; methods ; Female ; Humans ; Male ; Middle Aged ; Rectal Neoplasms ; pathology ; surgery ; Young Adult

OBJECTIVETo investigate the restoration of erectile function by reconstructing cavernous nerves (CN) with small intestinal submucosa (SIS) grafts.

METHODSWe prepared SIS grafts, established rat models and divided the models into a CN ablation, a sham-operation and an SIS graft group. The CNs at both sides were severed with 1 cm ablated in the first group, and 0.5 cm removed in the third, followed by reconstruction with the SIS grafts. Three months after surgery, the apomorphine test was performed to evaluate the erectile function, and then all the rats were sacrificed to detect the expression of nNOS in the penis.

RESULTSPenile erection was observed in 72.73% (8/11) of the rats for (1.07 +/- 0.89) times within 30 min in the SIS graft group, as compared with 0% (0/11) of the rats for (0.00 +/- 0.00) times in the CN ablation group (P < 0.01), and 90.91% (10/11) of the rats for (2.19 +/- 1.17) times in the sham-operation group (P < 0.01). The number of nNOS nerve fibers was significantly larger in the SIS graft than in the CN ablation group (70.36 +/- 10.09 versus 22.09 +/- 4.76, P < 0.01), but both were significantly smaller than that of the sham-operation group (90.81 +/- 5.69, P < 0.01).

CONCLUSIONThe SIS grafting technique contributes to the recanalization of the severed CN and restoration of erectile function in rats after surgical injury.

Animals ; Erectile Dysfunction ; surgery ; Intestinal Mucosa ; transplantation ; Intestine, Small ; Male ; Nerve Regeneration ; Nerve Tissue ; injuries ; surgery ; Penile Erection ; Penis ; innervation ; Rats ; Rats, Sprague-Dawley