Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation.

PURPOSE: This study aimed to investigate the interactions between posaconazole (POS) and intravenously/orally administered cyclosporine A (CsA) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: We included 118 allogeneic HSCT patients who received CsA and POS simultaneously between January 2017 and June 2020 in this study. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) before and after POS initiation was compared. RESULTS: After the initiation of POS, the level of CsA increased 1 to 2 times in 66% (78/118) of patients compared to those without POS. However, the CsA C/D ratio increased by more than threefold in 6% (7/118) of patients after POS initiation, with an increase of more than fourfold in two patients. The median C/D ratio of CsA increased from 0.89 to 1.23 (P < 0.001) and 0.78 to 1.22 (P < 0.001) after POS initiation when CsA was administered intravenously and orally, respectively. In patients who received POS at the time of transition from intravenous to oral CsA, the value increased from 1.01 to 1.38 (P = 0.001). The route of administration had no significant effect on the change in the CsA C/D ratio (P = 0.615). Additionally, we observed the time required for the C/D ratio to reach a plateau after POS initiation was similar on days 13, 8, and 15 under various scenarios. CONCLUSION: POS treatment increased blood CsA levels. A large variability was found in the fold-change in the CsA C/D ratio. Therefore, CsA doses should be adjusted by closely monitoring the blood levels of CsA after POS initiation.

Clinical characteristics, treatment, and long-term outcomes in children suffering from benign convulsions with mild gastroenteritis: a retrospective study.

BACKGROUND: Benign convulsions with mild gastroenteritis (BCWG) is a common condition in children in Asia and is generally not associated with pH or electrolyte imbalances. When BCWG is diagnosed, a lumbar puncture is usually recommended to rule out potential intracranial infections. This study examined the clinical characteristics of BCWG and evaluated the necessity of lumbar puncture. METHODS: Medical records of children admitted to the First Hospital of Jilin University with BCWG between January 2018 and May 2019 were reviewed and analyzed. Children were stratified by rotavirus positivity or lumbar puncture status. Clinical characteristics and long-term outcomes were compared between groups. RESULTS: A total of 51 children were included in the analyses (55.1% rotavirus [HRV] positive). The average age of convulsion onset was 21.12 ± 7.44 months, the male-to-female ratio was 1.8:1, and convulsions occurred primarily between October 2018 and April 2019. The main clinical presentations of BCWG were convulsions, vomiting, diarrhea, and fever. Convulsions occurred predominantly two days after diagnosis of gastroenteritis, were mainly generalized tonic-clonic with 88.2% of children having ≤ 3 convulsions per episode, and had a mean duration of 2.0 minutes (interquartile range [IQR]: 1.0, 3.0). Children with BCWG had mild metabolic acidosis (HCO3- 17.82 ± 3.63 mmol/L) with an elevated anion gap (AG; 20.98 ± 3.00 mmol/L), mild hyponatremia (134.56 ± 2.85 mmol/L), and slightly increased levels of creatine kinase myocardial band (CKMB). HRV + children had more severe acidosis and higher CKMB levels. Cerebrospinal fluid (CSF) samples collected via lumbar puncture were normal. No developmental abnormalities were noted as assessed by the Social Life Ability Scale. CONCLUSIONS: BCWG is a situation-related seizure, with clinical presentations of tonic-clonic or focal convulsions and mild gastroenteritis (vomiting, diarrhea). Mild metabolic acidosis and hyponatremia may exist. The prognosis of the disease is favorable; lumbar puncture and long-term antiepileptics are unnecessary and should not be recommended.

Analysis of gene expression profiles at different stages during preadipocyte differentiation in rabbits.

Excessive accumulation of fat is harmful to human health. The preadipocyte differentiation is a critical process of fat development. Studying the expression profiles of genes related to preadipocyte differentiation contributes to understanding of the mechanism of fat accumulation. Despite being considered an ideal animal model for studying adipogenesis, little is known about the gene expression profiles at different stages during preadipocyte differentiation in rabbits. In the present study, rabbit preadipocytes were cultured in vitro and induced for differentiation, and gene expression profiles of adipocytes collected at days 0, 3, and 9 of differentiation were analyzed by RNA-seq. We identified 1352 differentially expressed genes (DEGs) when comparing day 3 with day 0 and identified 888 DEGs when comparing day 9 with day 3. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the PPAR signaling pathway and PI3K-Akt signaling pathway were significantly enriched by the DEGs that up-regulated within the period of day 0 - day 3, and the GO terms and KEGG pathways that were associated with cell cycle were enriched by the DEGs that up-regulated within the period of day 3 - day 9. The DEGs that specifically up-regulated within the period of day 0 - day 3 might play roles in the cytoplasm, and the DEGs that specifically up-regulated within the period of day 3 - day 9 might act in the nucleus. The protein-protein interaction (PPI) network constructed by DEGs showed that hub node genes might modulate rabbit preadipocyte differentiation via regulating cell cycle.

Sudden Death From Ruptured Intracranial Vascular Malformations During Mechanical Asphyxia: A Domestic Violence Case Report.

Smothering and manual strangulation are not uncommon in domestic violence against women; however, no report on the combination of mechanical asphyxia and intracranial vascular malformations has been previously published. We report a middle-aged woman who was smothered and manually strangled by her husband and subsequently died from subarachnoid hemorrhage due to ruptured intracranial vascular malformations, rather than direct mechanical asphyxiation. Smothering and manual strangulation are considered provocative conditions for rupture and contributory causes of death. In this case study, we underline the importance of meticulous autopsy in cases of mechanical asphyxia and intracranial hemorrhage. Exclusion of underlying diseases that may have caused or contributed to death is also required, despite serious asphyxiation signs and neck injuries. Postmortem angiography is a valuable complement to autopsy to detect vascular pathology, with good prospects for further development in China.

Therapeutic effect of the metaverse on mental health.

López del Hoyo et al collections reported the meta verse based on the virtual reality, augmented reality and artificial intelligence could be used in the therapy of mental health, although there were still some challenges. This manuscript reported that the meta verse is a prospective method to improve the prognosis of mental health problems.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Adverse drug interactions as a high-risk factor for lethal post-transplant complications in Chinese population.

Metabolism of triazole antifungal agents is highly competitive to conventional post-transplant immunosuppressants like cyclosporine A (CsA) via the cytochrome P450-dependent pathway. We present the first report on lethal complications that may arise due to this type of drug interaction. A retrospective survey identified 10 of 104 cases (9.62%) that suffered life-threatening complications associated with the interaction between CsA and itraconazole or voriconazole following allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center. According to the close drug monitoring, all 10 patients experienced supratherapeutic levels of CsA even with a preemptive CsA dosage reduction and prompt dose adjustment. Six patients developed grade I to III acute graft-versus-host disease (aGVHD) and eventually died from either idiopathic pneumonia syndrome or diffuse alveolar hemorrhage; another four patients died from CSA-associated neurological complications. Impaired hepatic and renal function was noted in only one of these 10 cases. The high frequency as well as the unpredictability of severe complications lead us to suggest that triazole should always be replaced by another antifungal medication (e.g., amphotericin B or Echincandins) while patients receive CsA after HSCT, especially in the Chinese population.

Low-intensity ultrasound directly modulates neural activity of the cerebellar cortex.

BACKGROUND: Low-intensity ultrasound is a noninvasive neuromodulation technique with the potential to focally manipulate deep brain activity at millimeter-scale resolution. However, there have been controversies over the direct influence of ultrasound on neurons, due to an indirect auditory activation. Besides, the capacity of ultrasound to stimulate the cerebellum remains underestimated. OBJECTIVE: To validate the direct neuromodulation effects of ultrasound on the cerebellar cortex from both cellular and behavioral levels. METHODS: Two-photon calcium imaging were used to measure the neuronal responses of cerebellar granule cells (GrCs) and Purkinje cells (PCs) to ultrasound application in awake mice. And a mouse model of paroxysmal kinesigenic dyskinesia (PKD), in which direct activation of the cerebellar cortex leads to dyskinetic movements, was used to assess the ultrasound-induced behavioral responses. RESULTS: Low-intensity ultrasound stimulus (0.1 W/cm2) evoked rapidly increased and sustained neural activity in GrCs and PCs at targeted region, while no significant changes in calcium signals were observed responding to off-target stimulus. The efficacy of ultrasonic neuromodulation relies on acoustic dose modified by ultrasonic duration and intensity. In addition, transcranial ultrasound reliably triggered dyskinesia attacks in proline-rich transmembrane protein 2 (Prrt2) mutant mice, suggesting that the intact cerebellar cortex were activated by ultrasound. CONCLUSION: Low-intensity ultrasound directly activates the cerebellar cortex in a dose-dependent manner, and thus serves as a promising tool for cerebellar manipulation.

Behavioral adaptation in an adoptive free-ranging female Tibetan macaque.

Adoption is an important form of allomaternal care in nonhuman primates, with implications for reproductive output and infant survival. Here, we report a kidnapping that became an adoption of a 3-week-old infant by a mother with her own infant in Tibetan macaques (Macaca thibetana). The adoptive mother nursed her "new" infant (allonursing), the first observation of this behavior in the species. The case provided a natural experiment for comparing how a female copes with a heavier burden of care for both her biological infant and another female's infant, compared to mothers caring for only one infant. Our results showed that the adoptive female spent more time foraging and resting, and less time in group social activity compared to females with a single infant. The adoptive female showed more instances of social bridging. Although the duration of post-bridging grooming received from group members decreased, the frequency of such grooming increased. We discuss this adoption with reference to possible factors involved in the evolution of adoption and allonursing behavior in Tibetan macaques.

Metabolomics Reveal the Regulatory Effect of Polysaccharides from Fermented Barley Bran Extract on Lipid Accumulation in HepG2 Cells.

Barley bran has potential bioactivities due to its high content of polyphenols and dietary fiber, etc. Fermentation has been considered as an effective way to promote the functional activity of food raw materials. In this study, polysaccharides from barley bran extract fermented by Lactiplantibacillus plantarum dy-1 (FBBE-PS) were analyzed, and its effects on lipid accumulation and oxidative stress in high-fat HepG2 cells induced by sodium oleate were evaluated. The results showed that the molecular weight decreased and monosaccharide composition of polysaccharides changed significantly after fermentation. In addition, 50 µg/mL FBBE-PS could reduce the triglyceride (TG) content and reaction oxygen species (ROS) level in high-fat HepG2 cells by 21.62% and 30.01%, respectively, while increasing the activities of superoxide dismutase (SOD) and catalase (CAT) represented by 64.87% and 22.93%, respectively. RT-qPCR analysis revealed that FBBE-PS could up-regulate the lipid metabolism-related genes such as ppar-α, acox-1 and cpt-1α, and oxidation-related genes such as nrf2, ho-1, nqo-1, sod1, cat, etc. The metabolomics analysis indicated that FBBE-PS could alleviate lipid deposition by inhibiting the biosynthesis of unsaturated fatty acids, which is consistent with the downregulation of scd-1 expression. It is demonstrated that fermentation can alter the properties and physiological activities of polysaccharides in barley bran, and FBBE-PS exhibited an alleviating effect on lipid deposition and oxidative stress in high-fat cells.

Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice.

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience.

Value of needle confocal laser microendoscopy combined with endobronchial ultrasound bronchoscopy in the diagnosis of hilar and mediastinal lymph node lesions.

Endobronchial ultrasound bronchoscopy (EBUS) and needle confocal laser endomicroscopy (nCLE) are techniques for screening benign and malignant lesions of the hilar and mediastinal lymph node (HMLN). This study investigated the diagnostic potential of EBUS, nCLE, and combined EBUS and nCLE in HMLN lesions. We recruited 107 patients with HMLN lesions who were examined by EBUS and nCLE. A pathological examination was performed, and the diagnostic potential of EBUS, nCLE, and combined EBUS-nCLE approach was analyzed according to the results. Among the 107 cases of HMLN lesions, 43 cases were benign and 64 cases were malignant on pathological examination, 41 cases were benign and 66 cases were malignant on EBUS examination; 42 cases were benign and 65 cases were malignant on nCLE examination; 43 cases were benign and 64 cases were malignant on combined EBUS-nCLE examination. The combination approach had 93.8% sensitivity, 90.7% specificity, and 0.922 area under the curve, which was higher than those of EBUS (84.4%, 72.1%, and 0.782, respectively) and nCLE diagnosis (90.6%, 83.7%, and 0.872, respectively). The combination approach had a higher positive predictive value (0.908), negative predictive value (0.881), and positive likelihood ratio (10.09) than that of EBUS (0.813, 0.721, and 3.03, respectively) and nCLE (0.892, 0.857, and 5.56, respectively), whereas, the negative likelihood ratio was lower than that for EBUS (0.22) and nCLE (0.11). No serious complications occurred in patients with HMLN lesions. To summarize, the diagnostic efficacy of nCLE was better than EBUS. The EBUS-nCLE combination is a suitable approach for diagnosing HMLN lesions.

Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice.

Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma-aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR-PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIRGABA+-PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIRGABA+-PVT pathway alleviates pain, whereas inhibiting the activities of the ZIRGABA+-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABAAR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIRGABA+-PVT pathway acts through GABAAR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.

Isolation and characterization mesenchymal stem cells from red panda (Ailurus fulgens styani) endometrium.

Endometrial mesenchymal stem cells (eMSCs) are undifferentiated endometrial cells with self-renewal, multidirectional differentiation and high proliferation potential. Nowadays, eMSCs have been found in a few species, but it has never been reported in endangered wild animals, especially the red panda. In this study, we successfully isolated and characterized the eMSCs derived from red panda. Red panda eMSCs were fibroblast-like, had a strong proliferative potential and a stable chromosome number. Pluripotency genes including Klf4, Sox2 and Thy1 were highly expressed in eMSCs. Besides, cultured eMSCs were positive for MSC markers CD44, CD49f and CD105 and negative for endothelial cell marker CD31 and haematopoietic cell marker CD34. Moreover, no reference RNA-seq was used to analyse the eMSCs transcriptional expression profile and key pathways. Compared with skin fibroblast cell group, 9104 differentially expressed genes (DEGs) were identified, among which are 5034 genes upregulated, 4070 genes downregulated and the top 20 enrichment pathways of DEGs in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes Genomes (KEGG) mainly associated with G-protein coupled receptor signalling pathway, carbohydrate derivative binding, nucleoside binding, ribosome biogenesis, cell cycle, DNA replication, Ras signalling pathway and purine metabolism. Among the DEGs, some representative genes about promoting MSCs differentiation and proliferation were upregulated and promoting fibroblasts proliferation were downregulated in eMSCs group. Red panda eMSCs also had multiple differentiation ability and could differentiate into adipocytes, chondrocytes and hepatocytes. In conclusion, we, for the first time, isolated and characterized the red panda eMSCs with ability of multiplication and multilineage differentiation in vitro. The new multipotential stem cell could be beneficial not only for the germ plasm resources conservation of red panda, but also for basic or pre-clinical studies in the future.

Genome-wide analysis of microRNA and mRNA expression signatures in hydroxycamptothecin-resistant gastric cancer cells.

AIM: To investigate the involvement of microRNAs (miRNAs) in intrinsic drug resistance to hydroxycamptothecin (HCPT) of six gastric cancer cell lines (BGC-823, SGC-7901, MGC-803, HGC-27, NCI-N87, and AGS). METHODS: A sulforhodamine B (SRB) assay was used to analyze the sensitivity to HCPT of six gastric cancer cell lines. The miRNA and mRNA expression signatures in HCPT-resistant cell lines were then identified using DNA microarrays. Gene ontology and pathway analysis was conducted using GenMAPP2. A combined analysis was used to explore the relationship between the miRNAs and mRNAs. RESULTS: The sensitivity to HCPT was significantly different among the six cell lines. In the HCPT-resistant gastric cancer cells, the levels of 25 miRNAs were deregulated, including miR-196a, miR-200 family, miR-338, miR-126, miR-31, miR-98, let-7g, and miR-7. Their target genes were related to cancer development, progression and chemosensitivity. Moreover, 307 genes were differentially expressed in HCPT-resistant cell lines, including apoptosis-related genes (BAX, TIAL1), cell division-related genes (MCM2), cell adhesion- or migration-related genes (TIMP2, VSNL1) and checkpoint genes (RAD1). The combined analysis revealed 78 relation pairs between the miRNAs and mRNAs. CONCLUSION: Hierarchical clustering showed that the miRNA and mRNA signatures in our results were informative for discriminating cell lines with different sensitivities to HCPT. However, there was slightly lower correlation between the expression patterns of the miRNA and those of the predicted target transcripts.

Late-onset Leigh syndrome without delayed development in China: A case report.

BACKGROUND: Leigh syndrome (LS) is one of the most common mitochondrial diseases in infants and children. LS often manifests as early-onset with delayed phenotypic development. However, late-onset LS with normal development and white matter lesions in the brain is rarely reported, thereby highlighting the phenotypic variability of LS expression. CASE SUMMARY: We report a 12-year-old boy who presented with an unusual late-onset and fulminant form of LS that is maternally inherited without developmental delay. The patient was admitted to the hospital with symptoms of ptosis and somnolence, and died within 2 mo. Analysis of peripheral blood leukocytes showed a homoplasmic m.9176T>C mutation in the patient. Magnetic resonance imaging also revealed lesions in bilateral white matter as well as symmetrical lesions in the basal ganglia and brain stem. The patient was diagnosed with LS. The patient was treated with vitamin C, vitamin D, and adenosine-triphosphate. The patient died within 2 mo of hospital admission. CONCLUSION: LS can present in both infants and older children with different phenotypes.

Case Report: m.13513 G>A Mutation in a Chinese Patient With Both Leigh Syndrome and Wolff-Parkinson-White Syndrome.

A number of causative mutations in mitochondrial and nuclear DNA have been identified for Leigh syndrome, a neurodegenerative encephalopathy, including m. 8993 T>G, m.8993 T>C, and m.3243A>G mutations in the MTATP6, MTATP6, and MT-TL1 genes, respectively, which have been reported in Leigh syndrome patients in China. The m.13513 G>A mutation has been described only a few times in the literature and not previously reported in China. Here we report the case of a 15-month-old boy who presented with ptosis and developmental delay and was diagnosed with Leigh syndrome and well as Wolff-Parkinson-White (WPW) syndrome. The m.13513 G>A mutation was found in DNA from blood. He was intubated due to respiratory failure and died at 23 months of age. The m.13513 G>A mutation in the ND5 gene of mitochondrial DNA is associated with Leigh syndrome and WPW syndrome; however, this is the first report of this mutation in a patient in China, highlighting the geographical and racial variability of Leigh syndrome.

[Effect of application at Shu-Mu acupoint on serum uric acid in hyperuricemic rats].

OBJECTIVE: To observe the effect of application at Back-Shu with Front-Mu acupoints on serum uric acid (SUA) and kidney uric acid transport related proteins in hyperuricemia rats, so as to explore the mechanism of Shu-Mu acupoint application on treatment of hyperuricemia. METHODS: SD rats were randomly divided into blank control, model, vaseline application and medication application groups, with 8 rats in each group. The hyperuricemia rat model was established by gavage of potassium oxonate. Rats in the vaseline application group received application of vaseline at bilateral "Ganshu"(BL18) and "Qimen"(LI14), "Pishu"(BL20) and "Zhangmen"(LR13), "Shenshu" (BL23) and "Jingmen"(GB25). Rats in the medication application group received application of traditional Chinese medicine at the same acupoints. The contents of SUA and creatinine (SCr) were detected by automatic biochemical analyzer. H.E. staining was used to observe the pathological changes of kidney. And the protein expression levels of organic anion transporter 1(OAT1) and adenosine triphosphate binding cassette transporter G2(ABCG2) were detected by immunohistochemistry. RESULTS: Rats in the model group showed symptoms such as polydipsia, polyuria, loose stools, fatigue, weakness, etc. The renal tubules atrophied, and urate crystals can be seen in the lumen. Compared with the control group. the SUA content in the model group increased (P<0.01)and the expressions of OAT1 and ABCG2 protein in kidney decreased (P<0.01). After intervention and in comparison with the model group showed that, the diet, excretion function, and mental state of the rats in the medication application group returned to normal, and the pathological changes of the kidney tissue were alleviated, the SUA content was down-regulated(P<0.01)and the expression levels of OAT1 and ABCG2 in the kidney up-regulated (P<0.01). There was no statistically significant difference in the SCr content among the 4 groups (P＞0.05). CONCLUSION: Medication application at Shu-Mu points can effectively reduce the SUA level of hyperuricemia rats, which may be related to its effects in up-regulating the protein expressions of OAT1 and ABCG2 in the kidney and reducing the damage to the kidneys.

[Location of acupoint Xuanzhong(GB39)].

For a long time, there have been many opinions about the location of Xuanzhong(GB39) point in the academic field. The author analyzed the location of GB39 in the main acupuncture literature in ancient times, textbooks of universities and colleges of traditional Chinese medicine after the founding of the People's Republic of China, national standards and more influential acupuncture works. From ancient times to the evolution of the location of the point, it is believed that the point should be located 3 cun above the lateral malleolus, between the tibial anterior ridge and the anterior edge of the fibula.

Projecting neurons in spinal dorsal horn send collateral projections to dorsal midline/intralaminar thalamic complex and parabrachial nucleus.

Itch is an annoying sensation that always triggers scratching behavior, yet little is known about its transmission pathway in the central nervous system. Parabrachial nucleus (PBN), an essential transmission nucleus in the brainstem, has been proved to be the first relay station in itch sensation. Meanwhile, dorsal midline/intralaminar thalamic complex (dMITC) is proved to be activated with nociceptive stimuli. However, whether the PBN-projecting neurons in spinal dorsal horn (SDH) send collateral projections to dMITC, and whether these projections involve in itch remain unknown. In the present study, a double retrograde tracing method was applied when the tetramethylrhodamine-dextran (TMR) was injected into the dMITC and Fluoro-gold (FG) was injected into the PBN, respectively. Immunofluorescent staining for NeuN, substance P receptor (SPR), substance P (SP), or FOS induced by itch or pain stimulations with TMR and FG were conducted to provide morphological evidence. The results revealed that TMR/FG double-labeled neurons could be predominately observed in superficial laminae and lateral spinal nucleus (LSN) of SDH; Meanwhile, most of the collateral projection neurons expressed SPR and some of them expressed FOS in acute itch model induced by histamine. The present results implicated that some of the SPR-expressing neurons in SDH send collateral projections to the dMITC and PBN in itch transmission, which might be involved in itch related complex affective/emotional processing to the higher brain centers.