Fumarate hydratase deficient uterine leiomyoma: a clinicopathological and molecular analysis of 80 cases / 中华病理学杂志

Objective: To investigate the clinicopathologic and molecular characteristics of fumarate hydratase (FH) deficient uterine leiomyoma. Methods: Eighty cases of FH deficient uterine leiomyoma were diagnosed from April 2018 to September 2022 in Department of Pathology, Peking University Third Hospital. Sanger sequencing of FH gene exons (exon 1-10) were performed on tumor tissues and matched non-tumor tissues/peripheral blood for all cases. FH immunohistochemistry were performed in 74 cases; S-(2-succino)-cysteine (2SC) were also detected by immunohistochemistry in five cases. Results: Patients' age ranged from 18 to 54 (36.0±7.5) years, with more than 60% exhibiting clinical symptoms of multiple and large leiomyomas (the median diameter was 70 mm). More than four histologic features, including staghorn vasculature, alveolar-pattern edema, bizarre nuclei, oval nuclei arranged in chains, prominent eosinophilic nucleoli with perinucleolar haloes and eosinophilic intracytoplasmic globules were observed in 98.5% (67/68) patients. The immunohistochemical sensitivity of FH and 2SC were 97.3% and 100%, respectively. Based on the Sanger sequencing results, the cases were divided into germline variant group (31 cases), somatic variant group (29 cases) and no variant group (20 cases). Sixty-nine percent (20/29) of the patients with FH germline variation had clear family history. Conclusions: Clinical features, histological morphology, FH and 2SC immunohistochemistry and Sanger sequencing have their own significance and limitations in differential diagnosis of FH deficient uterine leiomyoma. In clinical practice, the above information should be fully integrated and studied for accurate pathologic diagnosis and selection of patients with FH germline variation.

Application of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain / 中国当代儿科杂志

OBJECTIVES@#To study the clinical efficacy of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain.@*METHODS@#A retrospective analysis was performed on the medical data of 30 children with the chief complaint of chronic abdominal pain who were admitted from August 2019 to May 2021. All the children were found to have inflammation of the appendix or intracavitary stool and fecalith by ultrasound and underwent ultrasound-guided endoscopic retrograde appendicitis therapy. The medical data for analysis included clinical manifestations, endoscopic findings, white blood cell count, neutrophil percentage, length of hospital stay, and cure rate.@*RESULTS@#Among the 30 children with chronic abdominal pain, there were 13 boys (43%) and 17 girls (57%), with a mean age of (9±3) years (range 3-15 years) at diagnosis. The median duration of the disease was 12 months, and the median length of hospital stay was 3 days. The children had a median white blood cell count of 6.7×109/L and a neutrophil percentage of 50%±13%. Fecalith and a large amount of feces were flushed out of the appendix cavity for 21 children (70%) during surgery. The follow-up rate was 97% (29/30), and the median follow-up time was 11 months (range 5-26 months). Of the 29 children, abdominal pain completely disappeared in 27 children (93%).@*CONCLUSIONS@#Ultrasound-guided endoscopic retrograde appendicitis therapy is effective in children with chronic abdominal pain caused by feces or fecalith in the appendix cavity.

Effect of FcRn on in vivo pharmacokinetics of a novel monoclonal antibody against West Nile virus MIL94 / 中国药理学通报

Aim To investigate the effects of different species Fc receptors (FcRn) on pharmacokinetic characteristics of MIL94, a monoclonal antibody against West Nile virus developed by Academy of Military Sciences, which has a neutralizing effect on West Nile virus and whose maintenance time in vivo is closely related to its antiviral effect. Methods The pharmacokinetic characteristics of MIL94 in mice expressing FcRn of different species (wild-type mice, hFcRn mice and FcRn knockout mice) were compared-. Wild-type mice and FcRn knockout mice were injected intravenously with MIL94 respectively. HFcRn mice were randomly divided into four groups. Two groups were injected intravenously with MIL94, and the other two groups were injected intravenously with intravenous immunoglobulin (IVIG) and then intravenously with MIL94. Indirect ELISA was used to determine the MIL94 concentration in mouse serum. WinNonlin software was used to calculate the pharmacokinetic parameters. Results After intravenous injection with MIL94, the in vivo pharmacokinetics were basically linear. The distribution volume of MIL94 in animals was related to FcRn. The half-life in vivo varied greatly between different groups. Conclusions FcRn can affect the half-life of MIL94 in different species mainly via alternation of its elimination and distribution. It is expected that the half-life of FcRn in human will be longer than that in preclinical animals.

Effects of anesthesia mode on the perioperative period and postoperative outcome in patients with traumatic fractures / 解放军医学杂志

Objective To retrospectively analyze the effects of anesthesia mode on the perioperative period and postoperative outcome in patients with traumatic fractures. Methods A total of 699 patients with traumatic shoulder fractures and hip fractures, admitted in the Fourth Medical Center of PLA General Hospital from Mar. 2016 to Aug. 2018, were divided into general anesthesia (GA) group (n=331) and regional block anesthesia (RA) group (n=368) according to different anesthesia mode. The preoperative basic conditions, change rates of intra-operative mean arterial pressure (MAP) and heart rate (HR), amount of blood loss and transfusion, and postoperative outcome were recorded for analyzing whether different anesthesia methods affected the outcome of fracture patients in the real world. Results There was no significant difference in the preoperative comorbidity between the two groups (P>0.05); Compared with the GA group, patients in RA group were older (P0.05), but age analysis indicated that, regardless of the mode of anesthesia, the incidence of postoperative complications increases with age (P<0.05). Compared with GA, patients older than 80 years reduced the incidence of postoperative complications significantly when they chose RA, and the difference was statistically significant (P=0.039). Meanwhile, compared with GA group, patients in RA group was lower and shorter in preoperative time, operative time, length of stay and cost in hospital, showing statistical difference (P<0.05). Conclusions Although there was no significant difference in postoperative outcomes of patients with overall fractures under different anesthesia modes, postoperative complications will increase with age. The advantages of regional block anesthesia are mainly reflected in fracture patients ≥80 years.

Effect of eicosapentaenoic acid on mRNA expression of tight junction protein ZO-1 in intestinal epithelial cells after Escherichia coli LF82 infection / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection.</p><p><b>METHODS</b>The Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant.</p><p><b>RESULTS</b>After EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant inhibitory effect on the proliferation of Caco-2 cells in a dose-dependent manner. The survival rates of the cells were significantly lower than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant increase in cell apoptosis rate compared with the control group (P<0.05). The 6- and 12-hour E.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (P<0.05). The Caco-2 cells treated with E.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated Caco-2 cells (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed a reduction in the secretion of TNF-α with the increasing concentration of EPA and had significantly lower secretion than the Caco-2 cells treated with E.coli LF82 alone (P<0.05).</p><p><b>CONCLUSIONS</b>EPA can effectively prevent the destruction of tight junction of intestinal epithelial cells induced by E.coli LF82 infection and inhibit the secretion of inflammatory factors. Therefore, it has a certain protective effect on intestinal mucosal barrier.</p>

Rebound depolarization of substantia gelatinosa neurons and its modulatory mechanisms in rat spinal dorsal horn / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the rebound depolarization of substantia gelatinosa (SG) neurons in rat spinal dorsal horn and explore its modulatory mechanisms to provide better insights into rebound depolarization-related diseases.</p><p><b>METHODS</b>Parasagittal slices of the spinal cord were prepared from 3- to 5-week-old Sprague-Dawley rats. The electrophysiologic characteristics and responses to hyperpolarization stimulation were recorded using whole-cell patch-clamp technique. The effects of hyperpolarization-activated cyclic nucleotide gated cation (HCN) channel blockers and T-type calcium channel blockers on rebound depolarization of the neurons were studied.</p><p><b>RESULTS</b>A total of 63 SG neurons were recorded. Among them, 23 neurons showed no rebound depolarization, 19 neurons showed rebound depolarization without spikes, and 21 neurons showed rebound depolarization with spikes. The action potential thresholds of the neurons without rebound depolarization were significantly higher than those of the neurons with rebound depolarization and spikes (-28.7∓1.6 mV vs -36.0∓2.0 mV, P<0.05). The two HCN channel blockers CsCl and ZD7288 significantly delayed the latency of rebound depolarization with spike from 45.9∓11.6 ms to 121.6∓51.3 ms (P<0.05) and from 36.2∓10.3 ms to 73.6∓13.6 ms (P<0.05), respectively. ZD7288 also significantly prolonged the latency of rebound depolarization without spike from 71.9∓35.1 ms to 267.0∓68.8 ms (P<0.05). The T-type calcium channel blockers NiCl2 and mibefradil strongly decreased the amplitude of rebound depolarization with spike from 19.9∓6.3 mV to 9.5∓4.5 mV (P<0.05) and from 26.1∓9.4 mV to 15.5∓5.0 mV (P<0.05), respectively. Mibefradil also significantly decreased the amplitude of rebound depolarization without spike from 14.3∓3.0 mV to 7.9∓2.0 mV (P<0.05).</p><p><b>CONCLUSION</b>Nearly two-thirds of the SG neurons have rebound depolarizations modulated by HCN channel and T-type calcium channel.</p>

Hereditary Transthyretin Amyloidosis in Eight Chinese Families / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.</p><p><b>METHODS</b>Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed.</p><p><b>RESULTS</b>The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2.</p><p><b>CONCLUSIONS</b>Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.</p>

Research on allelopathic effects of phellamurine / 中国中药杂志

Conducted research on new allelochemicals phellamurine extracted from deciduous of Phellodendron amurense, which worked in allelopathy effect to seed germination and growth process of P. amurense and P. chinense in order to interpret the causes of rare seedlings of wild populations of P. amurense. Extracted and separated phellamurine from P. amurense deciduous, and treated the seeds of P. amurense and P. chinense in after-ripening stage and germination stage with different concentrations of phellamurine solution, then detection of the seed germination rate, germination index, seedling height, root length and seed vigor index to evaluate the allelopathic effect of phellamurine. The results show that: phellamurine solution at 0.30 g x L(-1) produce significant inhibition to seed after-ripening of P. amurense, and also the solution at 0.15 g x L(-1) produce significant inhibition to seeds germination of P. amurense; the solution at 0.15 g x L(-1) produce significant inhibition to seeds after-ripening and seeds germination of P. chinense, inhibition intensity increased with the concentration and enhanced. For both species, the presence of phellamurine can lower the seed germination rate, extend the germination time, reduce the ability of seedlings to adapt to the environment, thus the phellamurine may be one of the causes of rare seedlings in the wild population of P. amurense.

Genetic characterization of echovirus 25 isolated from Henan / 病毒学报

This research firstly reported the molecular analysis of ECHO25 (Entric Cytopathic Human Orphanviruses Type 25). To clarify molecular characteristics of the ECHO25 virus isolates in Henan Province and its relationship with the rest of world's isolates,the complete VP1 sequences of the 4 isolates in Henan were successfully amplified by RT-PCR and were compared with other ECHO25 isolates available from GenBank. Compared with the prototype strain JV-4, the nucleotide sequence identity was 79.2%-80.1%, and the amino sequence identity was 89.0%-92.4, the nucleotide sequence identity among the 4 strains isolates in Henan Province was 93.0%-99.0%, the amino sequence identity was 92.4%-97.5%. HN-01 and HN-26 strains had the highest level of homology, the nucleotide homology was 99.0%; All the 4 strains belonged to the B1 genotype.

Effect of interstitial cells of Cajal on gastrointestinal motility induced by motilin receptor agonist ABT-229 / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of interstitial cells of Cajal (ICC) on contraction of intestinal tract smooth muscle induced by motilin receptor agonist.</p><p><b>METHODS</b>Two kinds of smooth muscle segments were isolated from the duodenum and colon of rabbit. Both kinds of smooth muscle were divided into two groups: group a (normal ICC group of duodenum); group c (impaired ICC group of duodenum); group b (normal ICC group of colon); group d (impaired ICC group of colon), each group contained 20 segments. The impairment of ICC was induced by selectively destroying ICC in the smooth muscle via treatment with methylene blue plus light. Then the frequency and amplitude of contraction of group a and c, group b and d was compared. Then motilin receptor agonist (ABT-229) was added into the Krebs solution, the frequency and amplitude of smooth muscle contraction before and after adding ABT-229 were recorded and compared.</p><p><b>RESULTS</b>The electron microscopy demonstrated that ICC in methylene blue plus light group were destroyed; the smooth muscle cells and neuron scattered close to ICC were normal. In group a, the contraction frequency, (17.89 +/- 1.88) times/min, was significantly lower as compared with that measured after ABT-229 was added [(18.76 +/- 1.18) times/min (P > 0.05)]; the amplitude of group a was (343 +/- 28) mg, which was lower as compared with that after adding ABT-229 [(597 +/- 68) mg (P < 0.001)]; in group b, the frequency was (5.89 +/- 1.03) times/min, the amplitude was (724 +/- 85) mg, after ABT-229 was added, the construction frequency increased to (8.45 +/- 0.69) times/min (P < 0.001), and the amplitude was (897 +/- 89) mg (P < 0.05), which was not affected by pretreatment with TTX, however it could be weakened by nifedipine significantly. In group c and d, the rhythmic contraction almost disappeared: in group c the contraction frequency was (1.06 +/- 0.24) times/min, and the amplitude were (50 +/- 10) mg. In group d, the amplitude and frequency significantly decreased as compared with the normal group (P < 0.001), in group c, and d, no significant difference in amplitude and frequency was found between the values measured before and after adding ABT-229 (P > 0.05). After Ach (100 micromol/L) was added, both group c and d could generate contraction.</p><p><b>CONCLUSION</b>ICC may play an important role in the rhythmic contraction of intestinal tract. The promoting effect of motilin receptor agonist on intestinal tract may be mediated by ICC. ICC deficiency may cause functional impairment of gastrointestinal tract motivation. The medication may become ineffective when the number of ICC is reduced to a certain extent or the network of ICC is incomplete.</p>