OBJECTIVE:To discuss what service marketing strategies the pharmaceutical enterprises in China should choose in the face of more and more fierce competition in pharmaceutical markets.METHODS:The service characteristics of both prescription drugs and over-the-counter(OTC)drugs were analyzed and new conceptions in pharmaceutical marketing such as the development and application of the service marketing were introduced as well.RESULTS&CONCLUSION:Di?versity,standardization,materialization are the right way the pharmaceutical enterprises should follow in the prescription drugs services;however,standardization,mechanics,brands are necessary for the OTC drugs services.

Aim To investigate the role of locus coeruleus(LC)-norepinephrinergic system and sympathetic nervous system in immunosuppression under cold stress, using 6-hydroxydopamine(6-OHDA) as chemical sympathectomy.Methods Rats were maintained in cold chamber at 4℃ for 4 h.The 51Cr release assay from YAC-1 cells was used to determine the splenic NK cell activity, the double staining of ABC method was employed to observe the immunoreactive expression of Fos, arginine-vasopressin(AVP), oxytocin(OT) and tyrosine hydroxylase(TH), and conventional radioimmunoassay was used to measure plasma corticosterone (CORT) concentrations.Results Central sympathectomy with intracerebroventricular(i.c.v.) injection of 6-OHDA r educed significantly the elevation of plasma corticosterone level, the expressio n of Fos in hypothalamic paraventricular nucleus(PVN) and in locus coeruleus(LC ), as well as the suppression of NK activity induced by cold stress at 4℃ for 4 h. Peripheral sympathectomy with intraperitoneal (i.p.) injection of 6-OHDA al so reversed the cold stress-induced suppression of NK cytotoxicity, but without significant effect on Fos expression in brain. Double staining showed that amon g the Fos-positive neurons in PVN only a few co-expressed Fos and AVP or Fos a nd OT, while in LC the majority of Fos-positive neurons co-expressed Fos and T H.Conclusion The mechanism of suppression of NK activity induce d by cold stress may be mediated through HPA axis activated partially by central LC-norepinephrinergic system and through the peripheral sympathetic nervous system.

Objective To investigate the effects and the migration mechanisms of stromal derived factor-1 (SDF-1) and CXC chemokine receptor-4 (CXCR-4) in rats with white matter damage treated with human umbilical cord mesenchymal stem cells (hUC-MSCs).Methods A total of 108 three-day old Sprague-Dawley rats were randomly divided into the experimental group,control group and sham group.The left common carotid artery was ligated and then exposed to hypoxia of 6％ O2 and 94％ N2 in rats in the experimental and control groups.Rats in sham group were neither ligation nor hypoxia.After 24 hours,rats in the experimental group were administered 0.5 ml hUC-MSCs (1 × 106/ml) intraperitoneally,and rats in control and sham groups were administered 0.5 ml saline by the same way.Immunohistochemistry and reverse transcription-polymerase chain reaction were used to determine the expression of SDF-1 and CXCR-4 protein and mRNA in 5-,7-and 14-day-old rats.Analysis of variance and the LSD test were used for statistical analysis of the data.Results HE staining showed that,in 14 day-old rats of the experimental group,bilateral cerebral ventricles were similar with no cellular edema or necrocytosis.In the sham group,bilateral cerebral ventricles were also normal.However,in the control group,ventriculomegaly,cellular degeneration and necrocytosis were observed on the left side.On the 5th,7th and 14th day,SDF-1 protein levels were 0.15±0.06,0.24±0.01 and 0.12±0.01,and CXCR-4 protein levels were 0.35±0.16,0.60±0.21 and 0.72±0.25,respectively,in the experimental group; SDF-1 protein levels were 0.13 ± 0.01,0.16± 0.01 and 0.08± 0.01,and CXCR-4 protein levels were 0.18 ± 0.04,0.17 ± 0.09 and 0.25 ± 0.06,respectively,in the control group,and all were higher than those in the sham group (SDF-1 protein levels were 0.03 ± 0.01,0.04± 0.01 and 0.02±0.01; and CXCR-4 protein levels were 0.04±0.02,0.05±0.03 and 0.05±0.03,respectively) (LSD test,all P＜0.05).SDF-1 protein increased to a peak on the 7th day and decreased on the 14th day in the experimental group,however,these values were both higher than those in the control group (LSD test,both P＜0.05).CXCR-4 protein increased on the 5th day and continued to increase up to the 14th day in the experimental group,and these values were higher than those in the control group at the three time points (LSD test,all P＜0.05).In 5-,7-and 14-day-old rats,SDF-1 mRNA levels were 3.52 ± 0.33,4.18± 0.28 and 2.60± 0.21,respectively,in the experimental group,which were higher than those in the control group (2.07± 0.34,3.73 ± 0.28 and 2.08± 0.15,respectively),and were even higher than those in the sham group (0.99±0.17,1.00±0.16 and 1.31 ±0.32,respectively) (LSD test,all P＜0.05).In the experimental group,SDF-1 mRNA levels reached a peak on the 7th day,and on the 14th day,it decreased to the level lower than that on the 5th day (LSD test,all P＜0.05).In the control group,SDF-1 mRNA levels also reached a peak in 7-day-old rats,but not in 14-day-old rats,which was similar to 5-day old rats (LSD test,9＞0.05).In 5-,7 and 14-day-old rats of the experimental group,CXCR-4 mRNA levels were 1.32±0.29,1.75±0.36 and 2.33±0.49,respectively,higher than those in the sham group (1.00±0.16,0.94±0.16 and 0.81±0.14,respectively) and the control group (0.97±0.14,0.97±0.15 and 1.07±0.25,respectively) (LSD test,all P＜0.05).In the experimental group,CXCR-4 mRNA levels were higher in 14-day-old rats than that in 5-and 7-day-old rats (LSD test,both P＜0.05).Conclusions SDF-1/CXCR-4 may play a vital role in the migration of hUC-MSCs homing to damaged brain.

Objective:To compare the similarities and differences of clinical characteristics of human immunodeficiency virus (HIV)-negative and HIV-positive patients with talaromycosis marneffei (TSM).Methods:The clinical data of 175 inpatients diagnosed with TSM in First Affiliated Hospital of Guangxi Medical University from May 2012 to April 2019 were retrospectively analyzed. The patients were divided into HIV-positive group and HIV-negative group according to the results of HIV confirmation test. The clinical manifestations, laboratory examination indicators (white blood cell count, hemoglobin, albumin, CD4 + T lymphocyte count and C-reactive protein (CRP)) between the two groups were compared. Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Among 175 TSM patients, 85 were HIV-positive and 90 were HIV-negative patients. The main clinical manifestations of fever and lymphadenopathy in the HIV-positive group and HIV-negative group were 71 (83.53%) cases and 73 (81.11%) cases, 50 (58.82%) cases and 47 (52.22%) cases, respectively, and there were both no statistical differences ( χ2=0.175 and 0.771, respectively, both P>0.05), while respiratory symptoms, weight loss and subcutaneous masses were 62 (72.94%) cases and 81 (90.00%) cases, 73 (85.88%) cases and 56 (62.22%) cases, one (1.18%) case and 16 (17.78%) cases, respectively, the differences were all statistically significant ( χ2=8.514, 12.630 and 13.737, respectively, all P<0.01). Hemoglobin in HIV-positive group and HIV-negative group were 90.50 (77.00, 113.95) g/L and 88.65 (72.85, 99.93) g/L, respectively. The difference was statistically significant ( Z=2.023, P=0.043). The ratios of albumin<30 g/L, CRP>10 mg/L in the two groups were 69.41%(59/85) and 60.00%(54/90), 94.37%(67/71) and 94.19%(81/86), respectively, and the differences were both not statistically significant ( χ2=1.693 and 0, respectively, both P>0.05). The ratios of cases with white blood cell counts >10×10 9/L and CD4 + T lymphocyte count<50/μL in the positive and negative groups were 3.53%(3/85) and 81.11%(73/90), 80.77%(63/78) and 1.75%(1/57), respectively, the differences were both statistically significant ( χ2=107.095 and 82.467, respectively, both P<0.01). Conclusions:In TSM patients, HIV-negative with subcutaneous masses, and increased white blood cell counts are common. Decreased body weight and CD4 + T lymphocyte count<50/μL in HIV-positive patients are more common than HIV-negative patients.

Objective To investigate the alterations in oligodendrocyte and microglia and changes in neurobehavior after human umbilical cord mesenchymal stem cells (HUcMSCs) intervention on the newborn rat model of white matter damage (WMD) induced by hypoxia-ischemia.Methods After the operation of left common carotid artery ligation and 4 h hypoxia (6％ O2 and 94％ N2),twelve three-day-old Sprague-Dawley rats died and the remaining sixty rats were randomly divided into the experimental group and the control group.The first day was 0 to 24 h after birth.Rats of the experimental group were intraperitoneally injected the fourth generation HUcMSCs 1 × 106 (0.05 ml) on the third,fourth and fifth day respectively.At the same time,rats of the control group were intraperitoneally injected phosphate buffer (0.05 ml).Eight rats of each group were executed on the tenth and twenty first day respectively to detect the number of cells positive for myelin basic protein (MBP) and ectodermal dysplasia-1 (ED-1) staining by immunohistochemistry.Three rats of each group were executed on the tenth and twenty first day respectively to detect MBP and ED-1 expression by western blot.Eight rats of each group were weighed and underwent the neurobehavioral evaluation on the twenty eighth day.Data were analyzed using t test.Results On the tenth and twenty first day,the numbers of MBP-positive cells in the experimental group (11.8 ± 4.1 and 23.8± 8.1) were significantly higher than those in the control group (6.7±3.1 and 11.5 ± 5.8,t=-2.81 and 3.49,both P＜0.05) ; and the numbers of ED-1 positive cells in the experimental group (20.8 ± 3.4 and 19.1 ± 2.8) were significantly lower than those in the control group (32.8±4.2 and 29.5±5.2,t=6.23 and 4.93,both P＜0.01).On the tenth and twenty first day,MBP expressions in the experimental group (1.3 ± 0.1 and 1.1 ± 0.1) were higher than those in the control group (0.8±0.0 and 0.6±0.1,t=-7.53 and 6.68,both P＜0.01) ; and the ED-1 expressions in the experimental group (0.6±0.1 and 0.4±0.1) were lower than those in the control group (1.0±0.1 and 0.8±0.1,t=3.09 and 4.90,both P＜0.01).Weight on the seventh,tenth,fourteenth,twenty first and twenty eighth day in the experimental group [(15.0± 1.2),(16.6±0.9),(27.0± 1.6),(44.2±2.3) and (68.1 ±4.2) g] was significantly higher than that in the control group [(12.7 ± 1.6),(13.5 ± 2.0),(23.6 ± 1.9),(38.4± 0.9) and (60.0± 4.2) g,t=-3.11,-3.97,3.67,-6.52 and-3.72,all P＜0.05].On the twenty eighth day,the score of open field test in the experimental group was significantly higher than that in the control group (36.5 ± 2.9 vs 24.3 ± 3.6,t=7.36,P＜0.01).So was the hanging test (3.6± 1.0 vs 2.0±0.7,t=3.53,P＜0.01).In Cylinder test,the ratio of left/both and right/both forefeet in the experimental group were similar [(49.8± 13.3) ％ vs (41.4±5.9) ％,t=0.86,P＞0.05],but the ratio of left/both forefeet in the control group was higher than right/both [(49.5 ± 11.3) ％ vs (31.2±3.2) ％,t=4.38,P＜0.01].Conclusions HUcMSCs are able to enhance the number of oligodendrocytes while weaken the activity of microglias in the WMD newborn rat model,and to promote the physical development and improve the rat neurobehavior.

Objective To evaluate the impact of the re-modified Sugiura procedure on portal hemodynamics and liver function in cirrhotic patients with portal hypertension.Methods Forty patients with cirrhosis and portal hypertension who underwent the re-modified Sugiura procedure in the Yichang Second People's Hospital from June 2006 to October 2014 were studied.Changes in the free portal pressure (FPP),portal venous flow (PVF) and liver functions before and after operation were analyzed.Results (1) The FPP at different phases of the operation (after opening the abdomen,after splenectomy,and after devascularization) were (43.2 ± 1.8) cmH2O,(34.8 ± 1.6) cmH2O and (35.2 ± 1.7) cmH2O,respectively.There were significant differences in FPP between the phases of after splenectomy and after opening the abdomen,as well as after devascularization and after opening the abdomen (P ＜ 0.05).There was no significant difference in FPP between after devascularization and after splenectomy (P ＞ O.05).(2) The PVF,which were measured with Doppler sonography at 4 time points (preoperative 1 day,postoperative 10 days,postoperative 6 months,postoperative 18 months),were (1 420.4 ± 137.7) ml/min,(1 205.2 ± 126.7) ml/min,(875.8 ± 118.0) ml/min and (893.8 ± 114.7) n1/min,respectively.There were significant differences in PVF between postoperative 10 days and preoperative 1 day,between postoperative 6 months and postoperative 10 days,as well as between postoperative 18 months and preoperative 1 day (P ＜0.05).There was no significant difference in PVF between postoperative 18 months and postoperative 6 months (P ＞0.05).(3)The liver functions were evaluated using the Child-Pugh score at 4 time points (preoperative 1 day,postoperative 10 days,postoperative 6 months,postoperative 18 months).There were no significant differences among the time points,(P ＞ 0.05).Conclusion The re-modified Sugiura's procedure durably,appropriately and effectively reduced the PVF and FPP,but it did not have any negative effects on the liver functions of patients with cirrhosis.

OBJECTIVETo investigate the clinical features, surgical transcranial approaches and outcomes of giant pituitary adenomas.

METHODSA series of 112 consecutive cases of giant pituitary adenomas underwent microsurgery through transcranial approaches at People' s Liberation Army General Hospital were retrospectively analyzed. Of the 112 patients, 58 were male and 54 were female, with age ranging from 3 to 72 years(mean age 44. 3 years). There were 91 non-functioning adenomas and 21 hormone-secreting adenomas. The maximum tumor diameter varied from 4. 0 to 7. 2 cm, with mean diameter of 4. 8 cm. Unilateral subfrontal approach was chosen in 16 cases, pterional approach in 41 cases, anterior interhemispheric approach in 34 cases, transcallosal-interforniceal approach in 6 cases, transcortical- transventricular approach in 5 cases, combined approach in 6 cases and other approaches in 4 cases. Postoperative MRI and endocrine function were re-examined routinely to evaluate the therapeutic efficacy. Staged operation through transsphenoidal approach or adjuvant treatments including medical and radiation therapies were administered in patients with hormone-secreting adenomas when hormonal excess persisted after surgery and in patients with non-functioning adenomas who had postoperative MRI evidence of residual tumor.

RESULTSTotal removal of the lesion was achieved in 57 cases (50. 9%) , 26 patients (23. 2%) underwent subtotal resection, and 29 patients (25. 9%) underwent partial removal. Postoperative mortality occurred in 3 patients (2. 7%). Major surgical morbidity occurred in 38 patients (33. 9%). Vision was preserved or improved in 98 patients (87. 5%). The postsurgical follow-up period varied from 3 to 64 months (mean 19. 5 months) . Nineteen of the 21 patients with hormone-secreting adenomas were considered to be in hormonal remission, and 87. 2% of the cases were capable of normal work and life and 8 patients suffered recurrence during the followed-up period.

CONCLUSIONSSelection of appropriate transcranial approaches is the key to successful microsurgery for giant pituitary adenomas according to the morphological characteristics presented in image examinations and clinical symptoms. Staged transsphenoidal operation and/or adjuvant therapies including medical and radiation therapies offer the best chances to control the residual tumors after the maximal surgical removal of giant adenomas through transcranial approaches.

Adenoma ; surgery ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Microsurgery ; methods ; Middle Aged ; Neurosurgical Procedures ; methods ; Pituitary Neoplasms ; surgery ; Postoperative Period ; Retrospective Studies ; Young Adult

Objective To evaluate whether recombinant human erythropoietin (rh-EPO) could increase the angiogenic responses in preterm rat models with periventricular white matter damage (PWMD).Methods Three-day postnatal rats were divided into 3 groups randomly:the sham group,the hypoxic-ischemic (HI) group and the recombinant human erythropoietin(rh-EPO)treatment group.Rat pups underwent permanent ligation of the right common carotid artery followed by 60 mL/L O2 for 4 h or sham operation and normoxic exposure.Immediately after the HI,rats received a single intraperitoneal injection of rh-EPO (5 U/g)or saline.Angiogenesis-related cells (CD34 + cells),microvessel density (MVD)and arteriovenous related genes (ephrinB2 and EphB4)were examined at 48 h and 96 h after operation.Results At 48 h after operation,the proteins of CD34 in HI rats increased compared with the sham rats (HI group vs Sham group:0.54 ± 0.05 vs 0.42 ± 0.05,P ＜ 0.05).However,the MVD,the mRNA of ephrinB2 and EphB4 did not change (P ＞ 0.05).The proteins of CD34,the mRNA of ephrinB2 and EphB4 increased after rh-EPO treatment compared with HI rats.However,the MVD did not increase.As the proteins of CD34 increased further at 96 h after operation (HI group vs Sham group:0.85 ± 0.06 vs 0.62 ± 0.06,P ＜ 0.05),the MVD (3.14 ± 1.21 vs 1.50 ± 1.04),ephrinB2 (7.51 ± 1.89 vs 1.28 ± 0.24) and EphB4 (4.58 ± 0.82 vs 1.21 ± 0.22) also increased (all P ＜ 0.05).And the proteins of CD34 increased after administration of rh-EPO(EPO group vs HI group:0.98 ± 0.07 vs 0.85 ± 0.06,P ＜0.05) and MVD(EPO group vs HI group:4.71 ± 1.38 vs 3.14 ± 1.21,P ＜0.05) were increased after administration of rh-EPO.However,the ephrinB2 and EphB4 did not increased after administration of rh-EPO at 96h time point.Conclusion Endogenous regenerative response is triggered in the damaged tissues and rh-EPO increases the angiogenesis in model rats with PWMD.

Primary central nervous system lymphoma (PCNSL) is a rare,extranodal form of non-Hodgkin lymphoma that is confined to the central nervous system.It mainly involves the deep brain white matter,the lateral ventricle and the corpus callosum.A decline in cognitive function and headache are the typical clinical manifestations of the disease.We report a patient with PCNSL in bilateral middle cerebellar peduncles,whose clinical manifestations were only dizziness and unstable walking.Brain MRI manifestations were not typical in early time,with symmetrical hypointensity lesions on T1-weighted imaging,hyperintensity lesions on T2-weighted imaging,and edema zone around on FLAIR imaging.Enhanced scan showed marginal contrast enhancement,but no significant occupying effect.These changes were similar to the multiple characteristics of multiple sclerosis.The history of autoimmune diseases and cerebrospinal fluid examination highly indicated demyelinating disease.The differences of clinical manifestations,MRI characteristics,diagnosis,treatment and prognosis between PCNSL in bilateral middle cerebellar peduncles and multiple sclerosis were analyzed to imorove the understanding of the disease in clinical practice.

Objective: To explore the clinical useness of intraoperative functional neuronavigation and fluorescent indocyanine green(ICG) angiography as well as electrophysiological evaluation during microsurgical resection of cerebral arteriovenous malformations (AVM). Methods: A series of 42 consecutive cases with AVM underwent microsurgery by intraoperative functional neuronavigation at Department of Neurosurgery of People′s Liberation Army General Hospital from January 2009 to February 2015 were retrospectively analyzed. Of the 42 patients, 29 were males and 13 were females aging from 4 to 62 years (mean age 32.6 years). Preoperative assessment included functional magnetic resonance imaging and diffusion tensor imaging to identify the relationship between lesions and eloquent areas. The results of images were integrated into three-dimensional datasets to achieve intraoperative microscopic-based functional neuronavigation during AVM resection. Operations involved in motor areas and corticospinal tract were performed under continuous electrophysiological monitoring. ICG angiography was performed at pre-dissection, post-clipping of the feeders, and post-resection of the nidus. FLOW 800 software presented a color map and ICG intensity-time curve to demostrate the vascular architecture. Postoperative digital subtraction angiography was re-examined routinely to evaluate the extent of resection. Clinical outcomes were evaluated with the modified Rankin Scale. Results: All patients underwent surgery under intraoperative navigation. Of the 42 patients, total resection was achieved in 36 cases (85.7%, 36/42) including 14 cases of AVM in eloquent areas. A total of 40 ICG angiographies were successfully performed among 11 patients. Average number of ICG injections per operation was 3.6 (ranging from 3 to 6). Feeders were visualized in 10 patients and drainers were visualized in 9 cases. The post-surgical follow-up period varied from 3 months to 70 months (mean 22.5 months). 83.8% of the patients returned to normal work and life during the followed-up period. Conclusion Combining intraoperative neuronavigation and electrophysiological monitoring, as well as fluorescent ICG angiography contribute to microsurgical resection of cerebral AVM effectively in selecting suitable patients, further avoiding neurologic compromise as well.