Long-term outcomes after hepatectomy of huge hepatocellular carcinoma: A single-center experience in China.

BACKGROUND: Currently, hepatectomy remains the first-line therapy for hepatocellular carcinoma (HCC). However, surgery for patients with huge (>10 cm) HCCs is controversial. This retrospective study aimed to explore long-term survival after hepatectomy for patients with huge HCC. METHODS: The records of 188 patients with pathologically confirmed HCC who underwent curative hepatectomy between 2007 and 2017 were reviewed; patients were divided into three groups according to tumor size: huge (>10 cm; n = 84), large (5-10 cm; n = 51) and small (<5 cm; n = 53) HCC. Kaplan-Meier analysis was used to assess overall survival (OS) and disease-free survival (DFS), and log-rank analysis was performed for pairwise comparisons among the three groups. Risk factors for survival and recurrence were analyzed using the Cox proportional hazard model. RESULTS: The median follow-up period was 20 months. Although the prognosis of small HCC was better than that of huge and large HCC, OS and DFS were not significantly different between huge and large HCC (P = 0.099 and P = 0.831, respectively). A family history of HCC, poor Child-Pugh class, vascular invasion, diolame, pathologically positive margins, and operative time ≥240 min were identified as independent risk factors for OS and DFS in a multivariate model. Tumor size (>10 cm) had significant effect on OS, and postoperative antiviral therapy and postoperative complications also had significant effects on DFS. CONCLUSIONS: Huge HCC is not a contraindication of hepatectomy. Although most of these patients experienced recurrence after surgery, OS and DFS were not significantly different from those of patients with large HCC after resection.

Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas.

Layer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM+) non-fast-spiking interneurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM+ interneurons were non-Martinotti. These morphologically distinct SOM+ interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are used across the cortex as building blocks to assemble cortical circuits.

Author Correction: Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Wnt4 is significantly upregulated during the early phases of cisplatin-induced acute kidney injury.

Wnt4 is a secreted growth factor associated with renal tubulogenesis. Our previous studies identified that renal and urinary Wnt4 are upregulated following ischemia-reperfusion injury in mice, but the roles of Wnt4 in other forms of acute kidney injury (AKI) remain unclear. Here, we investigated the changes in Wnt4 expression using a cisplatin-induced AKI model. We found that renal and urinary Wnt4 expression increased as early as 12 hours, peaked at day 4 following cisplatin-induced AKI and was closely correlated with histopathological alterations. By contrast, the serum creatinine level was significantly elevated until day 3, indicating that Wnt4 is more sensitive to early tubular injury than serum creatinine. In addition, renal Wnt4 was co-stained with aquaporin-1 and thiazide-sensitive NaCl cotransporter, suggesting that Wnt4 can detect both proximal and distal tubular injuries. These data were further confirmed in a clinical study. Increased urinary Wnt4 expression was detected earlier than serum creatinine and eGFR in patients with contrast-induced AKI after vascular intervention. This study is the first to demonstrate that increased expression of renal and urinary Wnt4 can be detected earlier than serum creatinine after drug-induced AKI. In particular, urinary Wnt4 can potentially serve as a noninvasive biomarker for monitoring patients with tubular injury.

Efficacy and safety of percutaneous transluminal pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension / 中华心血管病杂志

Objective: To explore the efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: This prospective single arm study included 19 CTEPH patients (7 male, age(56.3±12.5)years) admitted to Wuhan Asia Heart Hospital from January 2017 to June 2019 and received PTPA interventional therapy. Baseline data, including age, sex, WHO functional class, 6-minute walk distance (6MWD), NT-proBNP, right heart catheterization values, were collected. Patients received single or repeated PTPA. Number of dilated vessels from each patient was analyzed, patients were followed up for 24 weeks and right heart catheterization was repeated at 24 weeks post initial PTPA. All-cause death, perioperative complications, and reperfusion pulmonary edema were reported. WHO functional class, 6MWD, NT-proBNP, right heart catheterization values were compared between baseline and at 24 weeks follow up. Results: Nineteen CTEPH patients received a total of 56 PTPA treatments. The pulmonary artery pressure (mPAP) decreased from (40.11±7.55) mmHg (1 mmHg=0.133 kPa) to (27.53±4.75) mmHg (P<0.001), and the total pulmonary resistance (TPR) decreased from (13.00±3.56) Wood U to (5.48±1.56) Wood U (P<0.001), cardiac output increased from (3.19±0.63) L/min to (5.23±0.94) L/minutes (P<0.01) at 24 weeks post PTPA. The WHO functional class improved significantly (P<0.001), 6MWD increased from (307.08±129.51) m to (428.00±112.64) m (P=0.002), the NT-proBNP decreased at 24 weeks post PTPA (P=0.002). During the follow-up period, there was no death; hemoptysis occurred in 4 patients during the operation, none of which resulted in serious adverse clinical consequences. One patient developed reperfusion pulmonary edema and recovered after treatment. Conclusion: PTPA treatment is safe and can significantly improve the hemodynamics and WHO functional class of patients with CTEPH.

Pharmacological characterization of recombinant N-type calcium channel (Cav2.2) mediated calcium mobilization using FLIPR.

The N-type voltage-gated calcium channel (Ca(v)2.2) functions in neurons to regulate neurotransmitter release. It comprises a clinically relevant target for chronic pain. We have validated a calcium mobilization approach to assessing Ca(v)2.2 pharmacology in two stable Ca(v)2.2 cell lines: alpha1(B), alpha2delta, beta(3)-HEK-293 and alpha1(B), beta(3)-HEK-293. Ca(v)2.2 channels were opened by addition of KCl and Ca(2+) mobilization was measured by Fluo-4 fluorescence on a fluorescence imaging plate reader (FLIPR(96)). Ca(v)2.2 expression and biophysics were confirmed by patch-clamp electrophysiology (EP). Both cell lines responded to KCl with adequate signal-to-background. Signals from both cell lines were inhibited by omega-conotoxin (ctx)-MVIIa and omega-conotoxin (ctx)-GVIa with IC(50) values of 1.8 and 1nM, respectively, for the three-subunit stable, and 0.9 and 0.6nM, respectively, for the two-subunit stable. Other known Ca(v)2.2 blockers were characterized including cadmium, flunarizine, fluspirilene, and mibefradil. IC(50) values correlated with literature EP-derived values. Novel Ca(v)2.2 pharmacology was identified in classes of compounds with other primary pharmacological activities, including Na(+) channel inhibitors and antidepressants. Novel Na(+) channel compounds with high potency at Ca(v)2.2 were identified in the phenoxyphenyl pyridine, phenoxyphenyl pyrazole, and other classes. The highest potency at Ca(v)2.2 tricyclic antidepressant identified was desipramine.

β-Thalassemia among Newborns in Wuhan Region and Its Influence Factors / 中国实验血液学杂志

OBJECTIVE@#To investigate the screening of β-thalassemia among newborns in Wuhan region, so as to explore the influencing factors of Hb A in dried blood spot.@*METHODS@#Concentrations of Hb A,Hb A2,Hb F in the dried blood spots collected from 99 275 neonates in Wuhan region were analyzed by Sebia capillary electrophoresis. The screening result of β-thalassemia was interpretated accroding to the ratio of each group, the suspicious β-thalassemia newborns were recalled and the gene of thalassemia in those newborns was checked.@*RESULTS@#Among 99 275 newborns, 1 408 positive patients were found, and the positive rate of screening was 1.41%. A total of 350 patients with gene mutation were found among 709 β-thalassemia suspicious patients. There were significantly statistical differences of positive predictive value among Hb A levels in different groups and there were also significantly statistical differences of positive predictive values among gestational weeks in different groups. No significantly statistical differences were observed among different genetic defects and phenotypes of heterozygous β-thalassemia in Hb A concentrations. Postnatal day and gestational age were significantly and positively associated with Hb A concentrations.@*CONCLUSION@#The capillary electrophoresis is an effective screening method for β-thalassemia of full-term neonate. Postnatal day and gestational age is associated with the pencentage of Hb A.

Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy.

To date, two cannabinoid receptors have been identified, CB1 and CB2. Activation of these receptors with non-selective cannabinoid receptor agonists reduces pain sensitivity in animals and humans. However, activation of CB1 receptors is also associated with central side effects, including ataxia and catalepsy. More recently, a role for selective CB2 agonists in pain modification has been demonstrated. GW405833, a selective CB2 agonist, was recently reported to partially reverse the inflammation and hyperalgesia in a rat model of acute inflammation. In the current report, we extend the characterization and therapeutic potential of this compound. For the first time, we show that GW405833 selectively binds both rat and human CB2 receptors with high affinity, where it acts as a partial agonist (approximately 50% reduction of forskolin-mediated cAMP production compared to the full cannabinoid agonist, CP55,940). We also report for the first time that intraperitoneal administration of GW405833 (0.3-100 mg/kg) to rats shows linear, dose-dependent increases in plasma levels and substantial penetration into the central nervous system. In addition, GW405833 (up to 30 mg/kg) elicits potent and efficacious antihyperalgesic effects in rodent models of neuropathic, incisional and chronic inflammatory pain, the first description of this compound in these models. In contrast, analgesia, sedation and catalepsy were not observed in this dose range, but were apparent at 100 mg/kg. Additionally, GW405833 was not antihyperalgesic against chronic inflammatory pain in CB2 knockout mice. These data support the tenet that selective CB2 receptor agonists have the potential to treat pain without eliciting the centrally-mediated side effects associated with non-selective cannabinoid agonists, and highlight the utility of GW405833 for the investigation of CB2 physiology.

[Studies of complexing action mechanism in indirect determination of cysteine by FAAS with ZnS].

Each state of cysteine and zinc ion in aqueous solution at different pH conditions was calculated by computer, giving out the distribution curve. The mechanism of complexing action in indirectly determining cysteine by flame atomic absorption spectrometry with ZnS, and the influence of solution pH were studied. The state of cysteine and zinc ion in aqueous solution at different pH is different. The reason for forming the peak is the change of concentration of cysteine and zinc ion at different pH. The soluble complexing ion of -1 is composed valence cysteine Cys- and Zn(OH)2. The theoretical analysis is well conformable with the data determined from the experiments. The structure of complexing ion is [HS-CH2CH(NH2)-COO]2Zn(OH)2.

Serum nesfatin-1 changes in osteonecrosis of the femoral head / 中国组织工程研究

BACKGROUND: Nesfatin-1, a novel feeding regulator, has been found to be closely linked to orthopedic diseases in recent years. The correlation between Nesfatin-1 and osteonecrosis of the femoral head (ONFH) remains unclear. OBJECTIVE: To determine the changes in plasma Nesfatin-1 level in patients with ONFH and to study its correlation with the development of ONFH. METHODS: From May to December 2016, we enrolled 86 patients with ONFH who were hospitalized in the Hip Preserving Ward, No. 3 Orthopedic Department, the First Affiliated Hospital of Guangzhou University of Chinese Medicine (including 13 ARCO stage II, 26 ARCO stage III, and 47 ARCO stage IV) and 86 healthy controls. In the ONFH group, there were 26 cases of steroid-induced ONFH, 40 cases of alcoholic ONFH, 12 cases of traumatic ONFH, and 8 cases of idiopathic ONFH. The levels of Nesfatin-1 in peripheral venous blood were measured by enzyme-linked immunosorbent assay (ELISA). Comparison was performed between different ARCO stages, different etiologies as well as before and after collapse. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (No. 20140307), and each patient had signed an informed consent form prior to inclusion in the study. RESULTS AND CONCLUSION: Plasma Nesfatin-1 level was significantly higher in ONFH patients than healthy controls (P=0.000). There were insignificant differences among different etiologies (P=0.956), but significant differences among different ARCO stages (P=0.011) as well as before and after collapse (P=0.003). There was a positive correlation between plasma Nesfatin-1 level and ARCO stages. Receiver operator characteristic curve analysis showed that Nesfatin-1 level had sensitivity (52.05%) and specificity (92.31%) in the diagnosis of ONFH. These findings indicate that Nesfatin-1 is closely related to the development of ONFH. It can reflect the degree of necrosis, which can provide reference for clinical diagnosis and treatment of ONFH.

Transplantation of Autologous Peritoneum Using Ileal Seromuscular Flaps for Orthotopic Neobladder Reconstruction / 中国医学科学院学报

To develop an ideal surgical procedure for neobladder reconstruction in experimental porcine models. Six experimental female pigs weighting 28-33 kg underwent transplantation of autologous peritoneum for bladder reconstruction under general anesthesia.The flaps were used to reconstruct the orthotopic neobladder by suturing with the edges of the triangle and neck of the remnant bladder.The ureteral catheters were removed on the 5 postoperative day and the balloon catheter was removed on the 7 postoperative day.Voiding behaviour was monitored.The animals were euthanized at week 12 for routine pathology,immunohistochemistry,and electron microscopy. All the pigs survived after the surgery,and no postoperative complication such as peritonitis,intestinal obstruction,or urinary fistula was observed.All the peritoneum-ileum composite free valves survived after transplantation.Voiding behaviour was normal after catheter removal,and the urine was clear.At autopsy,reconstructed bladders were healthy.Pathological examination showed the neobladder had been covered by continuous urothelium while the peritoneum disappeared and showed no ileal mucosa regrowth and residual.Scanning electron microscope showed the transitional cells of neobladder were complete and orderly,and the urothelium around suture border was continuous and showed no malposition. Reconstruction of bladder by autologous peritoneum and ileal seromuscular flaps is an ideal approach in the experimental pigs as it can prevent regrowth of ileal epithelial cells and avoid the complications of conventional enterocystoplasty.Its clinical application deserves further investigations.

Effect of chitosan neurotoxin nanoparticles on permeability of blood brain barrier by intranasal administration / 中草药

Objective: To prepare chitosan neurotoxin nanoparticles (CS-NT-NP) and study its effect on the permeability of blood brain barrier and the serum levels of S100β by intranasal administration. Methods: A formamide extraction-ultraviolet spectrophotometry method was employed to determine the concentration of Evans blue (EB) in brain by different routes of administration and preparations. Qualitative analysis of fluorescence intensity and distribution of EB in brain tissue was performed by fluorescence microscopy. The serum S100β protein concentration was determined by ELISA. Results: Compared with the control group and NT group, CS-NT-NP could significantly increase the content of EB in the brain with time-effect relation and reached the peak at 120 min (P < 0.01); Compared with muscle injection and ip injection, intranasal administration could significantly increase the content of EB and reached peak time quickly. The results were consistent with the experimental results of qualitative analysis of fluorescence intensity and distribution of EB in brain tissue by fluorescence microscopy and S100β protein in serum. It was consistent with the experimental results of S100β protein. Conclusion: CS-NT-NP by intranasal administration can significantly increase the permeability of BBB, and further increase the drug concentration in the brain, which is a good carrier of macromolecular drugs into the brain.

Research progress of antipsychotics / 药学学报

Epidemiology indicates that schizophrenia affects approximately 8‰ of the world's population. The atypical (second and third generation) antipsychotics generally endowed with D2/5-HTHT2 receptors antagonism properties are commonly used as first-line drugs for the treatment of schizophrenia presently. They have been proven effective in the treatment of positive and negative symptoms of schizophrenia, but they are largely ineffective in the treatment of cognitive deficit. Moreover, the atypical antipsychotics are usually associated with cardiovascular and metabolic side effects such as QT prolongation and weight gain. To develop more potent antipsychotics with fewer side effects, more targets have been identified such as D3, glutamate, H3 receptors and PDE10A in recent years. Herein, the research progress of antipsychotics is reviewed.

Fourier Transform Infrared Microspectroscopy of Rat Kidney with Regard to Fa- tal Hyperthermia / 法医学杂志

OBJECTIVE@#To observe the chemical groups changing in rat kidney with regard to fatal hyperthermia by Fourier transform infrared microspectroscopy (FTIR-MSP) and to provide a new method to diagnose fatal hyperthermia.@*METHODS@#Rats were sacrificed by hyperthermia, brainstem injury, massive hemorrhage and asphyxiation and divided into groups. The renal samples were dissected immediately after death. The data of infrared spectroscopy in glomerulus were measured by FTIR-MSP.@*RESULTS@#The absorbances of 3290, 3070, 2850, 1540 and 1396 cm(-1) significantly increased (P < 0.05), and the ratios of Al650/A3290 and A1650/A1540 significantly decreased (P < 0.05) in group of hyperthermia.@*CONCLUSION@#FTIR-MSP can analyze the changes of chemical groups of kidney as an auxiliary diagnosis for discriminating hyperthermia with other causes of death.

Soft Rot of Rhizopus oryzae as a Postharvest Pathogen of Banana Fruit in Korea

Soft rot on banana fruit caused by Rhizopus oryzae was identified for the first time in Korea. Colonies were white to light brown and formed numerous sporangiospores. Optimum temperature for mycelial growth was 30degrees C. Sporangia were globose and 30~200 microm. Sporangiophores were usually straight, 8~20 microm, and rhizoids usually in groups of 3~5. Columella were globose to sub-globose and 90~110 microm. Sporangiospores were sub-globose or oval and 4~10 microm. Based on its mycological characteristics, molecular analysis, and pathogenicity to host plants, this fungus was identified as Rhizopus oryzae Went & Prisen Geerligs. This is the first report of soft rot on banana caused by Rhizopus oryzae in Korea.

Research progress of anti-influenza virus agents / 药学学报

Influenza is a major threat to millions of people worldwide. Vaccines and antiviral agents are two main options available to reduce the impact of the influenza virus, while anti-influenza agents are the most effective means to prevent the transmission of the highly contagious virus and to treat the epidemics of disease. At present, four anti-influenza agents have been approved by the FDA for the treatment of influenza, including two M2 protein ion channel inhibitors-amantadine and rimantadine and two neuraminidase inhibitors-zanamivir and oseltamivir. Arbidol hydrochloride, launched in Russia, is a potent inhibitor of influenza virus, too. Neuraminidase inhibitors could be classified generally by structure into six different kinds: sialic acid derivatives, benzoic acid derivatives, cyclohexene derivatives, cyclopentane derivatives, pyrrolidine derivatives and natural products. In this paper, recent progress in the research of the action mechanisms and structure-activity relationships of these anti-influenza virus agents were reviewed.

Study on osteogenic ability of chitosan/beta-tricalcium phosphate scaffold combined with human bone morphogenetic protein / 华西口腔医学杂志

<p><b>OBJECTIVE</b>Using chitosan (CS)/beta-tricalcium phosphate (TCP)/recombinant human bone morphogenetic protein (rhBMP)-2 for the reconstruction of rabbits' mandible defect, to prove the feasibility of CS/beta-TCP as an injectable bone tissue engineering scaffold material.</p><p><b>METHODS</b>Twenty-four New Zealand white rabbits were randomized into 4 groups on average: Experimental group 1 embedding CS/beta-TCP/rhBMP-2, experimental group 2 embedding CS/ beta-TCP, control group 1 embedding autograft bone group, control group 2 embedding nothing. At 2, 4 and 8 weeks after surgery, all rabbits were executed group by group. The new bone growth situations were observed with hematoxylin-eosin staining and immunofluorescence microscopy, the bone mineral density was detected by bone sonometers.</p><p><b>RESULTS</b>After 2, 4, 8 weeks, there was significant difference among the areas of bone regeneration of all groups. The effect of experimental group 1 was better than experimental group 2. There was significant difference at different times, the areas of bone regeneration was gradually increased with time. The area of stained yellow in experimental group 1 was larger, the area of stained red was smaller. The quantities of bone density in experimental group 1 at every time after surgery were significantly higher than experimental group 1 and control group 2, but had no statistical significance with control group 1.</p><p><b>CONCLUSION</b>CS/beta-TCP/rhBMP-2 has good biocompatibility, degradability and the capacity of guided and inducing osteogenesis. CS/beta-TCP as a good injection of carrier could become a promising carrier for rhBMP-2 and potential new degradable biological material for repairing bone defect in clinical application.</p>

Design and parallel synthesis of piperidine libraries targeting the nociceptin (N/OFQ) receptor.

Based on literature structures, we proposed a pharmacophore for NOP receptor ligands and used it as a guide for the design of a focused piperidine library and an optimization library. Potent NOP receptor agonists and antagonists were obtained from these libraries as well as a few potent, mu selective agonists.

Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor.

Small molecule mu agonists based on the 4-phenyl piperidine scaffold were designed and synthesized to further investigate the therapeutic potential of loperamide analogs. The resulting compounds show excellent agonistic activity towards the human mu receptor with interesting SAR trends within the series.

Effects of supracondylar fractures of humerus treated by three different surgical methods / 中国骨伤

<p><b>OBJECTIVES</b>To research the effects of supracondylar fractures of humerus treated by three different surgical methods.</p><p><b>METHODS</b>There were 103 patients with supracondylar fractures of humerus including 58 male and 45 female. The age was from 3 to 12 years old with the average of 7.4 years. To divide the cases into three groups by the operative approach in the humerus, the inside approach were in 37 cases (group A), the outside in 35 cases (group B) and the rear in 31 cases (group C). Comparing the reduction of the stretching and bending function of elbow joint and incidence of elbow varus.</p><p><b>RESULTS</b>All patients were followed-up for 1.5 to 8 years after operation with the average of 32 months. The reduction of stretching and bending function of elbow joint occurrenced in 6 cases in group A, 6 cases in group B and 25 cases in group C, the incidenc of group C were obvious more than group A and B (P < 0.01). The elbow varus occurred in 8 cases in group A, 17 cases in group B and 7 cases in group C, the incidence of group B were obviously more than group A and C (P < 0.05).</p><p><b>CONCLUSION</b>There are different effects between three kinds of operative approaches in the humerus. The incidence of outside group is higher on the varus of elbow. The incidence of rear group is higher on the ability of elbow joint stretching and bending. The effect of inside group is sure on the operative approach in the humerus.</p>