[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

[Progress of researches on symbionts in the management of mosquito-borne infectious diseases].

Mosquitoes are the main vectors of many infectious diseases, including malaria and yellow fever, which seriously threaten human health across the world. In addition to the use of chemical insecticides, genetic control is a new attempt to currently available interventions used for mosquito vector control. In terms of ecological safety, however, symbiotic control as a novel approach has been proposed for mosquito control. Since there are multiple symbiotic microflora inhabiting in a variety of tissues of mosquitoes, including the digestive tract, they may affect the transmission of mosquito-borne infectious diseases through affecting the lifespan, reproductive competence, and vector competence of the host. In this review, the interactions between symbionts in mosquitoes were summarized, and the research progress of mosquito-associated symbionts in the management of mosquitoborne infectious diseases was reviewed.

Effect of appetite-conditioned reflex stimulation on early enteral nutrition tolerance after surgery.

OBJECTIVE: This study aimed to discuss the effects of appetite-conditioned reflex stimulation on the early enteral nutrition (EEN) tolerance, complications, and postoperative hospital stay in patients who underwent surgery. METHODS: Seventy patients who underwent laparoscopic radical resection of colorectal cancer surgery in our hospital between February and December 2017 were randomly divided into a stimulated appetite group (experimental group, including visual stimulation, nasal stimulation, taste stimulation and hearing stimulation) and a control group (n = 35). Both groups received EEN. EEN tolerance, complications, and postoperative hospital stay were then compared between the groups. RESULTS: Sixty-six patients, including 34 in the experimental group and 32 in the control group, completed the relevant experiment. The experimental group had significantly lower incidence rates of nausea, vomiting, bloating, use of prokinetic drugs, and gastric tube replacement (P < 0.05), and shorter tolerable regular eating time (5.0 ± 1.0 d vs 6.4 ± 1.9 d, P < 0.05) and postoperative hospital stay (7.0 ± 2.0 d vs 8.0 ± 1.8 d, P < 0.05) than the control group. No significant difference in complication rate was detected (P > 0.05). CONCLUSION: Appetite-conditioned reflex stimulation can improve EEN tolerance, decrease the risk of complications, and shorten ordinary diet recovery time and hospital stay.

Treatment of patients with primary myelofibrosis using dasatinib.

OBJECTIVE: Primary myelofibrosis (PMF) is a chronic clonal myeloproliferative neoplasm. It is associated with a poor prognosis, with a median survival time of approximately five years. Thus far, there are no specific targeted drugs for PMF. In this study, we evaluated the efficacy and safety of dasatinib, a second-generation tyrosine kinase inhibitor, in six PMF patients. PATIENTS AND METHODS: From June 1, 2015 to February 29, 2016, six patients with PMF in our department were enrolled into this trial. The efficacy and safety of 100 mg/d (50 mg twice daily) dasatinib were investigated in these patients. RESULTS: For patients who experienced adverse drug events, the dose was reduced to 70 or 50 mg/d, whereas for those who tolerated the drug well, the dosage was increased to 140 mg/d (70 mg twice a day). Of the six patients, two achieved bone marrow histologic remission, five showed symptomatic improvement, and one reached a stable condition. No severe hematological or non-hematological adverse events were observed thus far. CONCLUSIONS: Dasatinib treatment may be beneficial to patients with PMF and resulted in significant improvements in splenomegaly, clinical symptoms, physical condition, and quality of life. Therefore, we regard it as an effective therapy for PMF.

Magnetic resonance imaging and microsurgical treatment of intramedullary hemangioblastoma of the spinal cord.

Thirteen cases of intramedullary hemangioblastoma of the spinal cord are reported. The tumors were diagnosed with radiological studies, especially magnetic resonance imaging. Microsurgery was used to achieve gross total removal of the tumors in all cases. Signs and symptoms improved in 84.6% of the patients after surgery. The authors describe the diagnosis and microsurgical techniques for the excision of intramedullary hemangioblastoma of the spinal cord. This disease should be differentiated from hydromyelia, intramedullary ependymoma, and vascular malformation of the spinal cord. Total removal of the tumor is recommended.

Surgical treatment of solid brain stem tumors in adults: a report of 22 cases.

BACKGROUND: Brain stem tumors in adults are infrequent. Most reports of surgical treatment for these tumors involve partial tumor removal in highly selected patients. A more aggressive approach for removing tumors, especially solid and intrinsic ones, has been controversial. METHODS: Twenty-two adult patients with brain stem tumors were surgically treated. Surgical techniques, potential risks, and selection of appropriate treatment were evaluated. RESULTS: Tumors were totally or subtotally removed in 20 patients and only partially removed in two patients. Serious complications such as respiratory disturbances and circulatory dysfunction occurred in 10 patients. Eight patients with these complications recovered after appropriate treatments. Upon discharge, most signs and symptoms improved in 17 patients. CONCLUSION: Most brain stem tumors, except for malignant gliomas and small ventral tumors, are amenable to an aggressive surgical approach. Exophytic medullary tumors that present dorsally comprise the most benign subgroup of brain stem tumors. Total removal can enhance survival, improve the patient's quality of life, and offer a favorable long-term prognosis. Appropriate management of postoperative complications is essential for good results.

Aggressive surgery for intramedullary tumor of cervical spinal cord.

BACKGROUND: Intramedullary tumors of the cervical spinal cord are common and many believe they are amenable to an aggressive approach. However, surgical removal of intramedullary tumors of the cervical spinal cord is still controversial because of the great risk of respiratory dysfunction or quadriplegia or both upon resection of the tumor. METHODS: We present a consecutive series of 58 patients who underwent surgical treatment for intramedullary tumors of the cervical spinal cord. Surgical results are analyzed to refine our indications for surgery and its timing. The roles of preoperative radiotherapy and posttherapeutic cord appearance and function are discussed. RESULTS: Tumors were totally resected in 50 (86.2%), subtotally in seven and partially in one patient. Forty-five (77.6%) patients had improved neurologic status postoperatively. Intramedullary tumors in the cervical area have better results from surgery than intramedullary tumors in other levels of the spine. Patients with moderate neurologic deficits can recover remarkably well after total tumor removal. Laser surgery is especially helpful for lipoma. Preoperative radiotherapy should be avoided because it is associated with difficult surgery and poor clinical outcome. The thin spinal cord can function surprisingly well. CONCLUSIONS: We conclude that intramedullary tumors of the cervical spinal cord are amenable to total surgical removal. Surgery is suitable when a patient presents with a moderate neurologic deficit. Proficient surgical technique for total tumor resection is necessary for good results. Preoperative radiotherapy contributes to difficult surgery and poor prognosis, and is not recommended.

A new crystal form of nateglinide.

AIM: To find a new crystal structure of S-form in nateglinide [N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine]. The XRD, IR patterns and data were given and the melting point was determined. METHODS: Phase analysis was performed by X-ray powder diffraction, IR and elemental analysis and the melting point was determined by differential scan calorimetry. RESULTS: S-form nateglinide is different from H-form or B-form. The melting point is 172.04 degrees C. CONCLUSION: The S-form nateglinide is a new crystal form.

The potential site of impaired gallbladder contractility in an animal model of cholesterol gallstone disease.

BACKGROUND & AIMS: Gallbladder contractility is decreased in cholesterol gallstone disease, but the mechanism underlining this defect is unclear. The aim of this study was to determine the cellular site of this defect in an animal model of cholesterol gallstone disease. METHODS: Ground squirrels were maintained for 28 days on either a control or a 1% cholesterol diet. Gallbladder contractile responses to several known agonists were measured in vitro using smooth muscle strips. RESULTS: Gallbladder contractility in response to cholecystokinin, bethanechol, and K+ was equally decreased in cholesterol-fed animals, in concert with an increased cholesterol saturation of gallbladder bile compared with controls. In contrast, the contractile responses to A-23187 (a calcium ionophore), cyclopiazonic acid (a selective, potent inhibitor of sarcoplasmic reticulum Ca2+ pump), and barium (a calcium analogue), which readily diffuse across the intact sarcolemmal membrane, remained the same in both groups. Dose responses to a G-protein activator, aluminum fluoride, were again not different between these two groups. CONCLUSIONS: The primary smooth muscle defect in this animal model of cholesterol gallstone disease does not reside in the intracellular signal transduction pathways or in the contractile apparatus but instead involves the sarcolemmal membrane.

Cisapride improves gallbladder contractility and bile lipid composition in an animal model of gallstone disease.

BACKGROUND: The hepatic secretion of supersaturated bile and gallbladder stasis are key events in cholesterol gallstone formation. The therapeutic value of cisapride, a prokinetic agent, was assessed in ground squirrels on a 1% cholesterol diet. METHODS: Biliary lipid secretion was measured directly and bile salt pool size assessed by isotope dilution ([14C]cholic acid). Gallbladder contraction was measured in vitro in response to cholecystokinin (CCK). RESULTS: Cholesterol-fed animals had a combined hepatic secretory defect (a 53% decrease in bile salt secretion and also a 31% increase in cholesterol secretion). Adding cisapride restored bile salt secretion to control levels but did not affect cholesterol secretion. In cholesterol-fed animals, the cholesterol saturation index of gallbladder bile more than doubled and cholesterol crystals developed; cisapride markedly reduced cholesterol saturation, thus preventing crystal formation. Gallbladder contractility, measured in vitro in response to CCK, decreased 23% in animals on the 1% cholesterol diet; cisapride restored the CCK dose-response curve to normal. The bile salt pool as assessed by isotope dilution was similar in all groups. CONCLUSIONS: Thus, lithogenic bile develops in this model because of reduced bile salt secretion and increased cholesterol secretion. Cisapride renders biliary lipid composition towards normal by enhancing gallbladder (and possibly intestinal) motility and cycling of the bile salt pool, thereby increasing bile salt secretion.

Inhibition of gallbladder emptying decreases cholesterol saturation in bile in the Richardson ground squirrel.

Impaired gallbladder emptying is frequent in cholesterol gallstone disease as well as in predisposing conditions like pregnancy and obesity. Gallbladder hypomotility is considered a pathogenic factor for gallstone formation, providing the residence time for cholesterol crystal nucleation, but any effect on the enterohepatic circulation of bile acids and subsequently on biliary lipid composition is unknown. Therefore, we studied the effect of prolonged suppression of gallbladder emptying with a cholecystokinin (CCK-A) receptor antagonist on bile formation in Richardson ground squirrels fed a trace versus a 1% cholesterol diet. Biliary lipid secretion was measured directly and bile acid pool size assessed by isotope dilution ([14C]-cholic acid). Gallbladder contraction was determined in vitro in response to CCK. The CCK-antagonist (MK-329) greatly inhibited gallbladder contraction in vitro and increased gallbladder fasting volume and bile acid pool size in vivo. It significantly lowered the cholesterol saturation index by 35% and 46% in hepatic bile and by 18% and 28% in gallbladder bile in the trace and cholesterol diet groups, respectively. Bile acid secretion and bile flow doubled with the CCK-receptor antagonist. Chronic CCK receptor antagonist-induced inhibition of gallbladder emptying increases bile acid secretion and thereby decreases cholesterol saturation in bile. Extensive biliary hypomotility thus leads to a more rapid cycling of bile acids by depriving the gallbladder of its function in the enterohepatic circulation.

The basis for progesterone impairment of gallbladder contractility in male guinea pigs in vitro.

Progesterone suppresses gallbladder smooth muscle function but its exact mechanism is unknown. We sought to determine the cellular site where progesterone impairs gallbladder smooth muscle. Sixty-four adult male guinea pigs were injected with either progesterone (2 mg/kg/day sc) or normal saline (controls) for 7 days. Dose-response curves of gallbladder strips to cholecystokinin (CCK), bethanechol, and potassium (K+) were constructed in vitro. To better define the basis for the progesterone effect, gallbladder contractile response was determined to specific agonists: aluminum fluoride and mastoparan (direct G-protein activators), cyclopiazonic acid (CPA), and a calcium ionophore (A-23187). Gallbladder from animals on progesterone exhibited a marked decrease in contractile response to CCK and bethanechol compared with controls (P < 0.05). Further, gallbladder contraction remained depressed (P < 0.05) in progesterone-treated animals, when the G protein was directly activated with aluminum fluoride and mastoparan. In contrast, the responses to K+ (acting independent of receptor G-protein) and to A-23187 and CPA (agonists that bypassed the membrane) were comparable in both groups (NS). It is concluded that progesterone directly inhibits gallbladder smooth muscle contractility in vitro to a standard hormone, CCK, and a cholinergic agent. Such depressed contraction is not due to an altered contractile machinery, since it is normal with agonists that act independently of G-protein activation. Progesterone thus interferes with signaling through the G-protein, either by directly becoming closely associated with the cell membrane or by indirectly perturbing its receptor products.

Inhibitory effect of bile salts on gallbladder smooth muscle contractility in the guinea pig in vitro.

BACKGROUND & AIMS: Impaired gallbladder emptying occurs in patients undergoing bile salt therapy for cholesterol gallstone dissolution and in patients with cirrhosis who have elevated serum bile salt concentrations. To determine if bile salts directly inhibit gallbladder contractility, isometric contraction of the guinea pig gallbladder was examined in vitro. METHODS: Contractile responses to cholecystokinin (CCK), bethanechol, KCI, and field stimulation were constructed alone and in the presence of selected bile salts: taurodeoxycholate (TDC), taurochenodeoxycholate, taurocholate, and tauroursodeoxycholate (TUDC). RESULTS: More hydrophobic bile salts, such as TDC (as low as 5 micromol/L), concentration-dependently depressed (P < 0.05) both CCK- and field stimulation-induced gallbladder contractions. More hydrophilic bile salts, such as TUDC, only caused a modest depression up to a concentration of 500 micromol/L. When 5 or 50 micromol/L of TUDC was added to the organ bath before the application of equalmolar TDC, the TDC-induced impaired gallbladder contractility was reversed. Thus, this inhibitory effect on gallbladder contraction depended on the hydrophobicity of bile salts and was also specific for certain stimuli such as CCK and field stimulation (mediated by cholinergic nerves, being abolished by atropine and tetrodotoxin). CONCLUSIONS: Such direct bile salt inhibition of CCK- and cholinergic nerve-induced gallbladder contraction may contribute to the deteriorating gallbladder emptying in patients undergoing bile salt therapy for stone dissolution and in cirrhotic patients who are at risk for gallstone formation.

Slow intestinal transit: a motor disorder contributing to cholesterol gallstone formation in the ground squirrel.

Impaired gallbladder motility is an established factor in cholesterol gallstone formation. We assessed whether altered small intestinal smooth muscle contractility with slow transit might potentiate gallstone formation by further impeding enterohepatic cycling of bile acids. Ground squirrels were fed a 1% or a trace (controls) cholesterol diet. Small intestinal transit was evaluated from 51Cr distribution in conscious, fasted animals 20 minutes after infusion into the proximal jejunum. Small intestinal and gallbladder smooth muscle contractility was determined in vitro. Biliary lipid secretion was measured from the cannulated common duct and the bile salt pool size calculated by isotope dilution. Gas-liquid chromatography (GLC) assessed bile salt profile. In animals on the 1% cholesterol diet, aboral transit was significantly delayed, the maximal contractile response to bethanechol was markedly increased (P <.05) with no change in median effective concentration in either circular or longitudinal muscle strips from both the jejunum and ileum, and the gallbladder contractile responses to bethanechol and cholecystokinin (CCK) were decreased. Cholesterol saturation index and the fraction of deoxycholic acid in the pool doubled, whereas the total bile salt pool size remained unchanged in cholesterol-fed animals. In this model, a high-cholesterol diet is associated with altered small intestinal smooth muscle contractility and prolonged small intestinal transit, in addition to diminished gallbladder contractility. The resulting sluggish enterohepatic cycling of bile salts, associated with expanded deoxycholate pool, contributes to cholesterol gallstone formation.

Sustained gallbladder stasis promotes cholesterol gallstone formation in the ground squirrel.

Although gallbladder stasis exists in most patients with cholesterol gallstones, it is unknown whether stasis is a causative factor of gallstone disease or merely a consequence of it. We studied the impact of sustained gallbladder stasis induced by a cholecystokinin (CCK)-A receptor antagonist (MK-329) on gallstone formation in ground squirrels fed either a trace or a high-cholesterol diet. MK-329 markedly inhibited gallbladder contraction in vitro in response to CCK (at EC100, control: 3.6 +/- 0.5 vs. MK-329: 1.1 +/- 0.3 g; P < .05) and increased gallbladder fasting volume in vivo (control: 462 +/- 66 vs. MK-329: 1,004 +/- 121 microL; P < .05). Whereas the high-cholesterol diet alone (1%-cholesterol diet + placebo) increased the cholesterol saturation index (CSI) in control animals (trace-cholesterol diet + placebo), MK-329 significantly (P < .05) decreased the CSI in both hepatic and gallbladder bile in animals on the trace-(trace-cholesterol diet + MK-329) as well as on the high-cholesterol diets (1%-cholesterol diet + MK-329). The mucin content of the mucus layer on the epithelial surface of the gallbladder wall more than doubled (P < .05) with the high-cholesterol diet; adding MK-329 to the latter group produced a further 82% increase (P < .05). The cholesterol diet + MK-329 group had the highest (100%) incidence of cholesterol crystals that were evident in fresh gallbladder bile, coincident with a shortened nucleation time (2.5 +/- 0.6 days; P < .05 vs. the cholesterol diet + placebo group, 5.8 +/- 1.0 days or the other 2 groups, >21 days). Bile from animals on the trace-cholesterol diet, whether or not receiving MK-329, lacked crystals in bile and exhibited a normal nucleation time (>21 days). Thus, stasis per se may lower the CSI, but its detrimental effect on the gallbladder predominates locally, and so accelerates cholesterol crystal formation in this model.

Altered migrating myoelectrical complex in an animal model of cholesterol gallstone disease: the effect of erythromycin.

BACKGROUND: The ground squirrel on a high cholesterol diet exhibits prolonged intestinal transit, a pathogenetic factor in cholesterol gallstone formation. AIMS: To examine the effect of a high cholesterol diet on the characteristics of the migrating myoelectrical complex (MMC) and the potential benefit of erythromycin. METHODS: Twenty four animals received either a trace (controls) or a 1% (high) cholesterol diet. After four weeks, five bipolar jejunal and terminal ileal electrodes were implanted. Seven days later, myoelectric activity was measured in conscious, fasted animals before and after treatment with erythromycin. Biliary lipid composition was assessed. RESULTS: Compared with controls, animals fed the high cholesterol diet exhibited a prolonged MMC cycle period (70 (6) versus 83 (3) minutes; p<0.05), whereas MMC migration velocity and the proportions of the MMC represented by phases I, II, and III were unchanged. Oral erythromycin significantly shortened the MMC cycle period in animals on the control and high cholesterol diet by 59% and 54% respectively, and increased the proportion of the cycle period occupied by phase III of the MMC in both dietary groups. Gall bladder bile became saturated with cholesterol and crystals developed in nine of 12 animals on the high cholesterol diet; controls had none. CONCLUSION: Animals fed a high cholesterol diet had a prolonged MMC cycle period. This, along with diminished gall bladder motility, impairs the enterohepatic cycling of bile salts and reduces their hepatic secretion, contributing to the formation of abnormal bile. Erythromycin initiated more frequent cycling of the MMC. Its therapeutic value in cholesterol gallstone formation warrants further evaluation.

Effect of the prokinetic agent, erythromycin, in the Richardson ground squirrel model of cholesterol gallstone disease.

Impaired gallbladder motility and delayed intestinal transit contribute to cholesterol gallstone formation by impeding the enterohepatic circulation of bile salts and causing gallbladder stasis. The therapeutic value of erythromycin, a prokinetic motilin analog, was evaluated in an animal model of gallstone formation. Eighty ground squirrels were fed either a trace- (control) or a high- (1%) cholesterol diet. Half of each diet group received either erythromycin stearate or placebo orally twice daily for 4 weeks. Biliary lipid secretion and bile salt pool size were determined via common duct cannulation. Gallbladder contractile response to cholecystokinin (CCK) was studied in vitro. Intestinal transit was evaluated in vivo by 51Cr marker. In the placebo-treated group, fed the high- versus the trace-cholesterol diet, bile salt secretion decreased (trace-cholesterol + placebo, 21.0 +/- 1.8 nmol/min/g liver vs. high-cholesterol + placebo, 9.3 +/- 1.4 nmol/min/g liver), cholesterol saturation index (CSI) doubled (trace-cholesterol + placebo, 0.61 +/- 0.06 vs. high-cholesterol + placebo, 1.30 +/- 0.04), nucleation time shortened (trace-cholesterol + placebo, > 21 days vs. high-cholesterol + placebo, 6.4 +/- 1.0 days), cholesterol crystals formed, gallbladder contractility diminished, and intestinal transit was delayed (each P < .05). Erythromycin treatment of animals on the high-cholesterol diet restored gallbladder contractility and intestinal transit to control levels, increased bile salt secretion, reduced the total bile salt pool, lowered the cholesterol saturation of bile, lengthened the nucleation time, and so reduced crystal formation (each P < .05). Erythromycin enhances gallbladder motility and hastens intestinal transit, promoting more rapid enterohepatic cycling of bile salts. This increases bile salt secretion, improves cholesterol solubility, and reduces crystal development.

Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle.

Elevated cholesterol decreases agonist-induced contractility and enhances stone formation in the gallbladder. The current study was conducted to determine if and how the electrical properties and ionic conductances of gallbladder smooth muscle are altered by elevated cholesterol. Cholesterol was delivered as a complex with cyclodextrin, and effects were evaluated with intracellular recordings from intact gallbladder and whole cell patch-clamp recordings from isolated cells. Cholesterol significantly attenuated the spontaneous action potentials of intact tissue. Furthermore, calcium-dependent action potentials and calcium currents were reduced in the intact tissue and in isolated cells, respectively. However, neither membrane potential hyperpolarizations induced by the ATP-sensitive potassium channel opener, pinacidil, nor voltage-activated outward potassium currents were affected by cholesterol. Hyperpolarizations elicited by calcitonin gene-related peptide were reduced by cholesterol enrichment, indicating potential changes in receptor ligand binding and/or second messenger interactions. These data indicate that excess cholesterol can contribute to gallbladder stasis by affecting calcium channel activity, whereas potassium channels remained unaffected. In addition, cholesterol enrichment may also modulate receptor ligand behavior and/or second messenger interactions.