[Clinical analysis of 16 cases of pulmonary epithelioid hemangioendothelioma].

Objective: To improve the diagnosis and treatment of pulmonary epithelioid hemangioendothelioma (P-EHE). Methods: Sixteen patients diagnosed with P-EHE in Fuzhou Pulmonary Hospital of Fujian Province from January 2009 to July 2020 were collected. Their gender, age, imaging findings, pathological characteristics, treatment protocols, survival and other clinical data were summarized and analyzed. Results: The ratio of male to female among the 16 patients was 1∶1; and the average age of onset was 47.75 years. Most cases of PEHE (9/16) were found by physical examination, while some cases developed respiratory symptoms such as cough, sputum, shortness of breath, hemoptysis, chest pain, etc. (7/16). In most patients the lesions were localized to the lungs (11/16), while bone metastasis (1/16), lymph node metastasis (1/16), and pleural metastasis (4/16) also occurred. The pathological tissues were obtained mainly through surgical thoracoscopy. Chest CT images showed multiple nodules in both lungs, with most of the nodules less than 2.0 cm in diameter, and calcifications were seen, while solitary nodules and masses were rare, and pleural metastases could be manifested as pleural thickening and pleural effusion. The pathological findings were well-defined eosinophilic nodules with irregularly arranged nest-like structures. Those eosinophilic nodules had few central cells and abundant peripheral cells, which extended into the alveolar cavity like papillae. The tumor cells were epithelioid with small atypia, and vacuoles and red blood cells could be seen in the cytoplasm of individual tumor cells. Immunohistochemically, the tumor cells were positive to CD34, CD31, Factor Ⅷ andvimentin (VIM). Follow-up of 0.5 to 11 years showed that four patients died, two lost to follow-up, and the rest of the patients were in good condition, with a median overall survival (OS) of 4.58 years. Conclusions: PEHE is a rare low-grade lung tumor with no specific clinical manifestations. It can be diagnosed with chest imaging and pathological immunohistochemistry. Moreover, there is currently no standard treatment for PEHE, and most patients have a good prognosis.

Management of vaccine cold chain delivery by international organizations / 上海预防医学

Most of serious vaccine-related adverse events in China are believed to be due to the poor management of vaccine cold chain delivery.It is an urgent need to strengthen the vaccine management system.To obtain a more comprehensive understanding of the management of vaccine cold chain delivery, including practical experience in specific regions and its supervision, we reviewed the documents/guidelines/literature, published by the WHO, GAVI and UNICEF in recent ten years, on vaccine cold chain delivery.The current study serves a good reference for the regulation, policy formulation and optimization of vaccine management.

Comparative analysis on the management of vaccine distribution in China and some other Asian countries / 上海预防医学

Objective To compare the framework of immunization programme and management of vaccine distributionin in China and some Asian countries, and further improve the immunization policy in China. Methods Using literature review, we compared the current status of immunization programme and vaccine distribution in China, Japan, Thailand, and Vietnam. Results Vaccine distribution has its own characteristics among Asian countries. Japan started early with a complete supervision system and compensation system. Thailand and Vietnam have also formed an efficient and complete cold chain transportation mode after implementing Expanded Programme on Immunization. Conclusion China can refer to the typical framework of immunization and experience of vaccine distributionfromsome Asian countries, which may improve vaccine accessand production links, standardize vaccine circulation market, and establish an efficient vaccine supervision and traceability system.

Experience of international vaccine surveillance systems management / 上海预防医学

We summarized the experiences of construction and management of vaccine safety surveillance systems in different countries and regions by using literature review, and then made the recommendations of strengthening vaccine surveillance system in China. In the study, we found that multiple existing national and regional vaccine surveillance systems, such as VAERS and EudraVigilance, can ensure vaccine safety through multi-sectoral surveillance, identification of adverse signals, and promotion of awareness of active reporting. However, the monitoring systems have some limitations, such as reporting bias and system decentralization. Therefore, China's vaccine monitoring system should establish an effective vaccine surveillance system, which achieves multi-sectoral, active, open to the public surveillance.

[Maternal-infant outcome of patients with OSAHS and gestational hypertension treated by CPAP].

Objective:To explore the clinical characteristics of obstructive sleep apnea hypopnea syndrome (OSAHS) diagnosed during pregnancy.To explore the effect on maternal and infant after treated with CPAP.Method:Data of 117 patients with OSAHS diagnosed by nocturnal blood oxygen saturation (SaO2) monitoring and PSG during pregnancy were analyzed retrospectively. All the 117 patients were voluntary and divided into intervention group [received continuous positive airway pressure (CPAP) treatment with good compliance under informed consent and conventional drug] 70 cases and control group(received conventional drug) 47 cases. Record the relevant data during the treatment about maternal and infant.Result:There was no statistical significance on the difference of cesarean delivery and postpartum hemorrhage in the pregnant women with mild OSAHS (P> 0.05), there was no statistical significance on the difference of cesarean delivery and postpartum hemorrhage in the pregnant women with moderate OSAHS (P> 0.05) and there were statistical significance on the difference of cesarean delivery and postpartum hemorrhage in the pregnant women with severe OSAHS (P< 0.05 or P< 0.01). There was no statistical significance on the difference of asphyxia neonatorum, fetal growth restriction and fetal distress in the pregnant women with mild OSAHS (P> 0.05), there were statistical significance on the difference of fetal growth restriction and fetal distress in the pregnant women with moderate OSAHS (P< 0.05), and there were statistical significance on the difference of asphyxia neonatorum, fetal growth restriction and fetal distress in the pregnant women with severe OSAHS (P< 0.05 or P< 0.01).Conclusion:Pregnant women who have OSAHS risk factors should be paid attention to during the perinatal care and nocturnal SaO2 monitoring or PSG should be performed in the suspected OSAHS patients. Strongly advise that those serious OSAHS patients should be treated by CPAP early before delivery. CPAP was a safe and effective treatment to OSAHS patients in pregnancy.

The role of ppGalNAc-T family in breast cancer development and progression.

Glycosylation of proteins is an essential process in all eukaryotes. Mucin-type O-linked glycosylation is an evolutionarily conserved protein modification as a kind of glycosylation of proteins. The role of O-glycosylation was well documented in multiple cancers. While in breast cancer, the enzymes that catalyzed the initiation of O-glycosylation remained elusive. In this review, we briefly introduced the process of the initiation of O-glycosylation and summarized the roles of enzymes that catalyzed the initiation step of O-glycosylation in the breast cancer carcinogenesis, development, and progression. Finally, we summarized some attempts exploring the therapy against aberrant O-glycosylation.

USPIO-related T1 and T2 mapping MRI of cartilage in a rabbit model of blood-induced arthritis: a pilot study.

Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation. The aims of this study were to investigate the effect of USPIO on cartilage T1 and T2 mapping, and to evaluate a proposed rapid vs. conventional T2 map method for imaging cartilage in a blood-induced arthritis model. Knees of nine arthritic (induction by intra-articular autologous blood injection) and six control rabbits were imaged over time (baseline, weeks 1, 5, 10) by 1.5 T MRI. All rabbits had USPIO (35-75 µmol Fe/kg)-enhanced MRI at each time point. T1 and T2 (conventional and rapid) maps and signal-to-noise ratios (SNR) were obtained pre- and post-USPIO administration. Cartilage biochemistry and histology were compared with MRI. Excellent correlations were noted between T1 map values and histologic scores at week 10 pre-USPIO (medial, r = 0.93, P = 0.0007; lateral, r = 0.87, P = 0.005) in the arthritic group, but not between T2 map and histology. Marginally and significant differences were observed between pre- and post-USPIO T2 values at weeks 5 (P = 0.06) and 10 (P = 0.02), but only with the administration of high USPIO doses in the arthritic group using the conventional method. No significant differences were noted between pre- and post-USPIO T1 values at any imaging time points. Cartilage T2 maps with short-TR and conventional protocols provided similar T2 values [(decreased trend)] (P > 0.05). Concomitant use of USPIO to T1 and T2 mapping of cartilage would not impair the identification of interval changes of T1 and T2 maps. Rapid T2 map provides similar results compared to conventional method, but its validation warrants further investigation.

Validation of connectivity-based thalamic segmentation with direct electrophysiologic recordings from human sensory thalamus.

Connectivity-based segmentation has been used to identify functional gray matter subregions that are not discernable on conventional magnetic resonance imaging. However, the accuracy and reliability of this technique has only been validated using indirect means. In order to provide direct electrophysiologic validation of connectivity-based thalamic segmentations within human subjects, we assess the correlation of atlas-based thalamic anatomy, connectivity-based thalamic maps, and somatosensory evoked thalamic potentials in two adults with medication-refractory epilepsy who were undergoing intracranial EEG monitoring with intrathalamic depth and subdural cortical strip electrodes. MRI with atlas-derived localization was used to delineate the anatomic boundaries of the ventral posterolateral (VPL) nucleus of the thalamus. Somatosensory evoked potentials with intrathalamic electrodes physiologically identified a discrete region of phase reversal in the ventrolateral thalamus. Finally, DTI was obtained so that probabilistic tractography and connectivity-based segmentation could be performed to correlate the region of thalamus linked to sensory areas of the cortex, namely the postcentral gyrus. We independently utilized these three different methods in a blinded fashion to localize the "sensory" thalamus, demonstrating a high-degree of reproducible correlation between electrophysiologic and connectivity-based maps of the thalamus. This study provides direct electrophysiologic validation of probabilistic tractography-based thalamic segmentation. Importantly, this study provides an electrophysiological basis for using connectivity-based segmentation to further study subcortical anatomy and physiology while also providing the clinical basis for targeting deep brain nuclei with therapeutic stimulation. Finally, these direct recordings from human thalamus confirm early inferences of a sensory thalamic component of the N18 waveform in somatosensory evoked potentials.

IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp.

IL-18, or IGIF (interferon-gamma inducing factor), is an IL-1-related, pro-inflammatory cytokine, which plays a pivotal role in systemic and local inflammation. We have identified and characterized IL-1H, a novel IL-1-related molecule. IL-1H appears to be expressed in most tissues with relatively high levels in testis, thymus and uterus. The IL-1H transcripts were stimulated by phorbol ester (PMA) in human cell lines (A431, THP-1 and KG-1) and peripheral blood mononuclear cells (HPBMC) and dendritic cells (NHDC). The protein sequence of IL-1H is mostly related to IL-1ra with a similarity of 36%. A short form of IL-1H was identified, and lacks a 40-amino acid segment in the amino-terminal region of the protein. When expressed in mammalian cells, two secreted polypeptides of IL-1H were identified: an uncleaved and a cleaved form starting with amino acid Val-46. Furthermore, IL-1H binds the IL-18 receptor, but not the IL-1 receptor. These findings suggest that IL-1H may be another ligand for the IL-18 receptor and a new player in the inflammatory and immune responses mediated by the IL-18/IL-18R axis.

Overexpression of the human 2-oxoglutarate carrier lowers mitochondrial membrane potential in HEK-293 cells: contrast with the unique cold-induced mitochondrial carrier CGI-69.

Using differential mRNA expression analysis, a previously uncharacterized gene was found to be up-regulated 2-fold in brown adipose tissue (BAT) of mice exposed to cold (4 degrees C) for 48 h. Contig and homology analysis revealed that the gene represents the murine orthologue to a sequence from a public database encoding a putative human protein (CGI-69). The presence of mitochondrial carrier domains in the human protein, its transmembrane topology and cold-induction of the mouse CGI-69 gene in BAT prompted an analysis of the idea that CGI-69 may represent a new uncoupling protein (UCP) functional homologue. However, transfection of human CGI-69 isoforms in HEK-293 cells yielded no change in mitochondrial membrane potential (Deltapsi(m)), despite localization of FLAG-tagged CGI-69 to mitochondria of MCF7 cells. Surprisingly, overexpression of the human 2-oxoglutarate carrier (OGC) protein (originally designed as a negative control) sparked a significant drop in Deltapsi(m), possibly signalling a previously unappreciated uncoupling activity for the OGC.

Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction.

Protein kinase C (PKC) inhibitors, chelerythrine (Chel, 0.6 mg) and polymyxin B (Poly B, 1.0 mg), and PKC activators, phorbol 12-myristate 13-acetate (PMA, 0.05 mg) and 1-oleoyl-2-acetyl glycerol (OAG, 0.1 mg), were used as probes to investigate the role of PKC in mediation of ischemic preconditioning (IPC) of noncontracting pig latissimus dorsi (LD) muscles against infarction in vivo. These drugs were delivered to each LD muscle flap (8 x 12 cm) by 10 min of local intra-arterial infusion. It was observed that LD muscle flaps sustained 43 +/- 5% infarction when subjected to 4 h of global ischemia and 24 h of reperfusion. IPC with three cycles of 10 min ischemia-reperfusion reduced muscle infarction to 25 +/- 3% (P < 0.05). This anti-infarction effect of IPC was blocked by Chel (42 +/- 7%) and Poly B (37 +/- 2%) and mimicked by PMA (19 +/- 10%) and OAG (14 +/- 5%) treatments (P < 0.05), given 10 min before 4 h of ischemia. In addition, the ATP-sensitive K(+) (K(ATP)) channel antagonist sodium 5-hydroxydecanoate attenuated (P < 0.05) the anti-infarction effect of IPC (37 +/- 2%), PMA (44 +/- 17%), and OAG (46 +/- 9%). IPC, OAG, and Chel treatment alone did not affect mean arterial blood pressure or muscle blood flow assessed by 15-microm radioactive microspheres. Western blot analysis of muscle biopsies obtained before (baseline) and after IPC demonstrated seven cytosol-associated isoforms, with nPKCepsilon alone demonstrating progressive cytosol-to-membrane translocation within 10 min after the final ischemia period of IPC. Using differential fractionation, it was observed that nPKCepsilon translocated to a membrane compartment other than the sarcolemma and/or sarcoplasmic reticulum. Furthermore, IPC and preischemic OAG but not postischemic OAG treatment reduced (P < 0.05) muscle myeloperoxidase activity compared with time-matched ischemic controls during 16 h of reperfusion after 4 h of ischemia. Taken together, these observations indicate that PKC plays a central role in the anti-infarction effect of IPC in pig LD muscles, most likely through a PKC-K(ATP) channel-linked signal-transduction pathway.

Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation.

Mitochondrial uncoupling proteins have been implicated in the maintenance of metabolic rate and adaptational thermoregulation. We recently reported the identification of a brain-specific mitochondrial uncoupling protein homologue, UCP4. Here we characterized another newly described member of the uncoupling protein family, termed UCP5 (also called BMCP1). UCP5 transcripts are present in multiple human and mouse tissues, with an especially high abundance in the brain and testis. Expression of UCP5 in mammalian cells reduces the mitochondrial membrane potential. Multiple isoforms of UCP5 were identified and exhibited tissue-specific distribution and different potency in reduction of membrane potential. Furthermore, the mRNA abundance of both UCP4 and UCP5 is modulated by nutritional status or temperature in a tissue-specific manner in mice. Brain UCP4 and UCP5 mRNA transcripts rose by 1.5- and 1.7-fold, respectively, and liver UCP5 expression increased by 1.8-fold in response to acute cold exposure. A high-fat diet increased UCP5 mRNA in liver by 1.6-fold selectively in the obesity-resistant A/J but not in the obesity-prone C57BL/6J mouse strain. Liver UCP5 expression decreased significantly with a 24 h fast and was restored to the normal level after refeeding. In contrast, brain transcripts for both genes were not significantly altered by fasting or high-fat diet. These findings are consistent with the notion that UCP4 and UCP5 may be involved in tissue-specific thermoregulation and metabolic changes associated with nutritional status.

Rapid mapping of protein functional epitopes by combinatorial alanine scanning.

A combinatorial alanine-scanning strategy was used to determine simultaneously the functional contributions of 19 side chains buried at the interface between human growth hormone and the extracellular domain of its receptor. A phage-displayed protein library was constructed in which the 19 side chains were preferentially allowed to vary only as the wild type or alanine. The library pool was subjected to binding selections to isolate functional clones, and DNA sequencing was used to determine the alanine/wild-type ratio at each varied position. This ratio was used to calculate the effect of each alanine substitution as a change in free energy relative to that of wild type. Only seven side chains contribute significantly to the binding interaction, and these conserved residues form a compact cluster in the human growth hormone tertiary structure. The results were in excellent agreement with free energy data previously determined by conventional alanine-scanning mutagenesis and suggest that this technology should be useful for analyzing functional epitopes in proteins.

High prevalence of hyperparathyroidism among peritoneal dialysis patients: a review of 176 patients.

OBJECTIVES: Parathyroid dysfunction continues to produce significant morbidity in dialysis patients. Since the introduction of low calcium dialysate for peritoneal dialysis (PD), no large studies have been done to determine the prevalence of parathyroid dysfunction in these patients. This study was done to assess the prevalence of parathyroid disease in the PD population and to determine the risk factors associated with this dysfunction. DESIGN: We analyzed data on 176 patients who received PD at a single center between August 1998 and February 1999. Clinical data, laboratory variables related to parathyroid function, and data pertaining to dialysis treatment and weekly drug dosing were obtained for each patient on two different occasions, approximately 3 months apart. Variables predictive of the development of parathyroid dysfunction were calculated by univariate and multivariate logistic regression analysis. RESULTS: Two-thirds of the patients surveyed had an abnormal intact parathyroid hormone (iPTH) level: 47% had an iPTH level more than three times normal, the mean was 54.6+/-35.4 pmol/L; 23% had an iPTH value below the upper limit of normal, here the mean was 3.6+/-1.8 pmol/L. Diabetic patients had lower iPTH levels (22.2+/-28.4 pmol/L) than nondiabetics (33.9+/-34.8 pmol/L) (p = 0.02). On multivariate regression analysis, we found that age, duration of dialysis, Kt/V, serum bicarbonate, and serum ionized calcium levels did not significantly affect parathyroid function. Hyperphosphatemia was the only factor that was associated with the development of secondary hyperparathyroidism in this study population (p = 0.029). CONCLUSION: There is a high prevalence of hyperparathyroidism in the current PD population. Phosphate control is suboptimal and hyperphosphatemia is an independent risk factor for the development of hyperparathyroidism.

Recurrence of hyperparathyroidism after total parathyroidectomy and autotransplantation in peritoneal dialysis patients.

OBJECTIVE: To evaluate the effectiveness of total parathyroidectomy (PTX) with autotransplantation in the treatment of secondary hyperparathyroidism (HPT), and to assess recurrence rate of HPT in this peritoneal dialysis (PD) population. DESIGN: A retrospective study in a single home PD unit. PATIENTS: Between 1994 and 1998, 19 of 574 patients on PD underwent PTX for treatment of secondary HPT. MAIN OUTCOME MEASURES: Clinical and biochemical improvement, recurrence of HPT, improvement in anemia post-PTX. RESULTS: Nineteen (3.3%) patients required PTX between 1994 and 1998. These 5 men and 14 women ranged in age from 22 to 66 years; they had been on maintenance PD pre-PTX for 47.5 +/- 38.1 months, and were followed for 26.1 +/- 15.5 months post-PTX. Sixteen patients had temporary hypocalcemia that was managed by oral (n = 10) or intravenous (n = 6) calcium supplements and calcitriol, while 3 patients had severe "hungry bone" syndrome postoperatively. One patient had recurrent laryngeal nerve palsy post-PTX. Bone pain disappeared in all 12 patients. Pruritus improved in 12/13 patients; fatigue improved in 15/16 patients. Comparison showed significant differences between hemoglobin and hematocrit values 1 month pre-PTX and 12 months post-PTX (p < 0.05). Parathyroid hormone (PTH) level in 15 (79%) patients returned to normal (< or = 7.6 pmol/L) during the first month post-PTX. In 5/12 (42%) patients, PTH level was < or = 7.6 pmol/L 2 years post-PTX, while in 2/12 (17%), PTH was > 22.8 pmol/L (three times normal) 2 years post-PTX, and 3/5 (60%) patients had a PTH > 22.8 pmol/L 3 years post-PTX. CONCLUSIONS: Total PTX with autotransplantation is associated with a tendency for recurrence of HPT. Our findings suggest that total PTX with autotransplantation may be an ineffective procedure in controlling HPT over the long term.

[Prognostic value of serum CA125 level in patients with advanced non-small cell lung cancer].

OBJECTIVE: To judge the prognostic value of serum CA125 level in patients with advanced non-small cell lung cancer. METHODS: Sixty-six untreated patients with advanced non-small cell lung cancer (NSCLC) confirmed histologically were studied. They received two to four cycles of chemotherapy, some of them combined with radiotherapy. All these patients were assayed for serum CA125 before treatment. The cut-off value of serum CA125 level was 35 U/ml. RESULTS: Increased serum CA125 levels were observed in 24 out of 66 patients (36.4%). Patients with increased serum CA125 levels had an average survival rate of 12.5% at 1 year and 0 at 2 years, whereas that of patients with normal serum CA125 levels was of 57.1% at 1 years, 14.3% at 2 years and 7.1% at 3 years. Cox proportion hazard multivariate analysis showed that the prognosis of patients was related to serum CA125 levels (P = 0.000) and effects of treatment (P = 0.046). CONCLUSION: CA125 can be used as an independent prognostic parameter in advanced NSCLC.

UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells.

Uncoupling proteins (UCPs) are a family of mitochondrial transporter proteins that have been implicated in thermoregulatory heat production and maintenance of the basal metabolic rate. We have identified and partially characterized a novel member of the human uncoupling protein family, termed uncoupling protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins. Unlike other known UCPs, UCP4 transcripts are exclusively expressed in both fetal and adult brain tissues. UCP4 maps to human chromosome 6p11.2-q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain.

[Adenosine is effective to improve the viability of the transverse rectus abdominis myocutaneous (TRAM) flap in the pig].

OBJECTIVE: The aim of this experiment was to investigate the adenosine treatment for augmentation of TRAM flap viability in pigs. METHODS: This TRAM flap model was based on the deep inferior epigastric vascular pedicle, with the center of the transverse skin pedicle attached to the underlying rectus abdominis muscle at the superior end of the muscle and extending bilaterally from its attached muscle. The transverse skin pedicle (6 x 30 cm) included a contralateral and ipsilateral random portion of skin. Prior to raising the TRAM flap, 1 mg, 2 mg or 5 mg adenosine was injected through the superior epigastric artery in the experiment group. RESULTS: Treatment with 2 mg or 5 mg adenosine increased skin viability of the transverse skin flap in the experiment group compared with the sham-operated control (P < 0.05, n = 5). CONCLUSION: Adenosine treatment through a dominant vascular pedicle prior to raising the TRAM flap is effective in augmenting skin viability of the flap.