Effects of water-sodium balance and regulation of electrolytes associated with antidiabetic drugs.

As the prevalence of diabetes rises, the use of antidiabetic drugs becomes more frequent. Thus, focusing on the effects of these drugs on water-sodium balance and electrolyte regulation is necessary. This review discusses the effects and the mechanisms behind them. Several sulfonylureas, such as chlorpropamide, methanesulfonamide, and tolbutamide, exhibit water-retaining properties. Other sulfonylureas, such as glipizide, glibenclamide, acetohexamide, and tolazamide, are not antidiuretic or even diuretic. Numerous clinical studies showed that metformin can reduce serum magnesium concentrations and may have an effect on the cardiovascular system, but the specific mechanism remains to be discussed. Different opinions exist about the mechanisms of thiazolidinedione-induced fluid retention. Sodium-glucose cotransporter 2 inhibitors can cause osmotic diuresis and natriuresis and elevated serum potassium and magnesium concentrations. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors can enhance urine sodium excretion. At the same time, increased urinary sodium caused by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors reduce blood pressure and plasma volume, thereby protecting the heart. Insulin has a sodium-retaining effect and is also associated with hypokalemia, hypomagnesemia, and hypophosphatemia. Several of the aforementioned pathophysiological changes and mechanisms have been discussed, and conclusions have been drawn. However, further investigation and discussion are still warranted.

[The effects of high risk of ovarian hyperstimulation syndrome and duration of embryo cryopreservation on perinatal outcomes of single live births in the first frozen embryo transfer cycle after whole embryo cryopreservation].

Objective: To investigate the effects of high risk of ovarian hyperstimulation syndrome (OHSS) and duration of embryo cryopreservation on perinatal outcomes of the first frozen-thawed cycle after whole embryo cryopreservation. Methods: The clinical data of 1 804 patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation and achieved singleton live births in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to June 2021 were retrospectively analyzed. According to whether there was high risk of OHSS in the oocyte retrieval cycle, the patients were divided into high-risk group (n=790) and non-high-risk group (n=1 014). The baseline data and perinatal outcomes were compared between the two groups. Multivariate linear regression was applied to analyze the relative factors affecting neonatal weight. And the high-risk group was divided into three subgroups according to different cryopreservation time: the embryos of 96 cycles with a cryopreservation time less than 60 days were defined as group A; the embryos of 587 cycles with a cryopreservation time around 60 to 120 days were defined as group B; the embryos of 107 cycles with a cryopreservation time more than 120 days were defined as group C. The perinatal outcomes were compared among the three groups. The measurement data in this study were represented byï¼»M（Q1，Q3）］. Results: The female age in the high-risk group was 30.0 (27.0, 32.0) years old, which was lower than that in the non-high-risk group 31.0 (29.0, 34.0) (P<0.001). The male age in high-risk group was 30.0 (28.0, 33.0), lower than that in non-high-risk group 32.0 (29.0, 35.0) (P<0.001). The birth weight of high-risk group [3 500.0 (3 200.0,3 800.0) g] was higher than that of control group [3 400.0 (3 150.0,3 800.0) g](P=0.045). Multivariate linear regression analysis showed that female BMI was correlated with neonatal weight, ß (95%CI) was 15.37(8.33, 22.41) (P<0.001), and the high risk of OHSS was not correlated with neonatal weight, ß (95%CI) was 19.40 (-38.07, 76.87) (P=0.508). There was significant difference in the incidence of low birth weight and very low birth weight among groups A, B and C (all P values<0.05), and the incidence of low birth weight and very low birth weight in group C was higher than that in group B (all P values<0.017). Conclusions: The risk of adverse perinatal outcomes in high-risk OHSS patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation was not increased. However, prolonged cryopreservation of embryos may lead to increased risk of low birth weight and very low birth weight.

[Diffuse midline glioma with H3K27 alteration in adults: a clinicopathological analysis].

Objective: To investigate the clinicopathological characteristics, pathological diagnosis and prognosis of diffuse midline glioma (DMG) with H3K27 alteration in adults. Methods: Twenty cases of H3K27-altered adult DMG diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2017 to 2022. All cases were evaluated by clinical and imaging presentations, HE, immunohistochemical staining and molecular genetics; and the relevant literature was reviewed. Results: The ratio of male to female was 1∶1, and the median age was 53 years (range from 25 to 74 years); the tumors were located in the brainstem (3/20, 15%) and non-brainstem (17/20, 85%; three in thoracolumbar spinal cord and one in pineal region). The clinical manifestations were non-specific, mostly dizziness, headache, blurred vision, memory loss, low back pain, limb sensation and/or movement disorders, etc. Microscopically, the tumors showed infiltrative growth, with WHO grade 2 (3 cases), grade 3 (12 cases), and grade 4 (5 cases). The tumors showed astrocytoma-like and oligdendroglioma-like, pilocytic astrocytoma-like and epithelioid-like patterns. Immunohistochemically, the tumor cells were positive for GFAP, Olig2 and H3K27M, and H3K27me3 expression was variably lost. ATRX expression was lost in four cases, p53 was strongly positive in 11 cases. Ki-67 index was about 5%-70%. Molecular genetics showed p. k27m mutation in exon 1 of H3F3A gene in 20 cases; BRAF mutation in two cases: V600E and L597Q mutation in one case each. Follow up intervals ranged from 1 to 58 months, and the survival time for brainstem (6.0 months) and non-brainstem (30.4 months) tumors was significantly different (P<0.05). Conclusions: DMG with H3K27 alteration is uncommonly found in adults, mostly occurs in non-brainstem, and can present in adults of all ages. Owing to the wide histomorphologic features, mainly astrocytic differentiation, routine detection of H3K27me3 in midline glioma is recommended. Molecular testing should be performed on any suspected cases to avoid missed diagnosis. Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.

[Clinicopathological features of polymorphous low-grade neuroepithelial tumor of the young].

Objective: To investigate the clinicopathological features and differential diagnosis of polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Methods: Five cases of PLNTY diagnosed at the First Affiliated Hospital and Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China from 2019 to 2021 were collected. All cases were evaluated using clinical and imaging data, histology, immunohistochemical staining and molecular genetics. The relevant literature was reviewed. Results: There were two male and three female patients, aged 10 to 39 years, with an average age of 25 years. Clinically, the tumors were in the temporal lobe (3 cases), the lateral ventricle (1 case) and the left head of caudate nucleus (1 case). The clinical manifestations included epilepsy in 3 cases, right visual disturbance in 1 case, and post-trauma incidental finding in 1 case. Microscopically, the lesions were characterized with infiltrative growth, cellular pleomorphism (oligodendroglioma-like cells were always present, with low-grade, pleomorphic nuclei) and variable calcifications. Immunohistochemically, the tumor cells were positive for GFAP and Olig2. They also showed intense and diffuse expression of CD34 while CD34 expressing ramified neural elements were present in regional cortex. Ki-67 proliferation index was less than 3%. Molecular genetics showed the BRAF V600E mutation in 2 cases, the PAK5-Q337R missense mutation in 1 case, the FGFR2-CTNNA3 fusion in 1 case, and the FGFR2-INA and FGFR2-PPRC1 concomitant fusion in 1 case. No postoperative chemoradiotherapy was given. Follow-up intervals ranged from 3 to 29 months while no recurrence or metastasis was identified. Conclusions: PLNTY is uncommon. A definite diagnosis of PLNTY relies on histopathological examination and molecular genetics. It is important to distinguish PLNTY from high grade gliomas and avoid overtreatment. The recently reported the PAK5-Q337R missense mutation and the FGFR2-PPRC1 gene fusion in PLNTY may help diagnose and understand the pathogenesis of PLNTY.

The morphological and histological study of chicken left ovary during growth and development among Hy-line brown layers of different ages.

Chicken ovaries are known to develop asymmetrically and only the left ovary fully develops. Although both have been greatly investigated, a gap in scientific reports is still felt between 2-mo-old and sexual maturity. In this study, we aimed at investigating the changes in components that occur during growth to analyze the morphohistological correlation between the left ovary and the follicle development at different age stages in Gallus domesticus. The ovaries were harvested from 60 chickens aged 1 and 3-wk-old, 1, 2, 3, and 4-mo-old (n = 10 per age group), then fixed in AAF solution. Hematoxylin-and Eosin protocol was used to stain the tissue for microscopic observations. Results revealed that the left ovary exhibited an ovarian tissue, a site of follicular growth that displayed various shapes from smooth to greatly indented as the follicles differentiated. Atretic follicles at various regression stages were noticed frequently as the chicks grew in age from 3-wk-old onward along with their differentiation. Rete ovarii, remnants from the male homologs were observed throughout the whole study showing epoöphoron, connecting rete, and gland-like structures that tend to diminish with age. The feature of the left ovary is closely related to the follicular developmental stage, and the bigger and differentiated the follicles are, the more indented and irregular its epithelium appears. Atresia is a normal physiological process that we observed throughout the whole study. Also that, rete ovarii do not spontaneously arise in the ovary but it develops and grows in juvenile chicken as well as in adult ones.

[Pulmonary artery intimal sarcoma: a clinicopathological analysis of three cases].

Objective: To investigate the clinicopathological characteristics, genetic features, diagnosis and differential diagnosis of pulmonary artery intimal sarcoma (PAIS). Methods: Three cases of PAIS were collected from Jiangsu Province People's Hospital (from February 2016 to November 2019). The clinical data, imaging examination, morphology, immunostaining, and molecular changes were retrospectively analyzed. Results: There were 1 male and 2 females (age: 32, 50, 60 years), who had symptoms of cough, asthma or chest tightness. Imaging findings indicated low density filling defects which were suspected as thrombus, embolism or myxoma. Grossly, the main tumor was located in the elastic arteries and their lobar branches, also extended into the atrium and ventricle, with lung parenchymal infiltration focally. Microscopically, tumor cells were predominantly composed of abundant spindle cells with obvious atypia and myxoid background, resembling fibroblastic or myofibroblastic differentiation. Active mitotic figures and necrosis could be seen in some areas. Immunohistochemical staining of vimentin was strongly positive, while pan-cytokeratin, S-100, desmin, Fli-1, CD31, SMA and ERG etc were variably positive only in focal areas. FISH detection showed amplification of MDM2 gene in three cases and EGFR gene in two cases. Metastatic lesions were found in one case by 18, 32 and 42 months after surgery respectively. There was no recurrence or metastasis in the other two cases. Conclusions: PAIS is one of exceptionally poor differentiated mesenchymal tumor that arises from the arterial intima of elastic pulmonary arteries. There was no definite differention in morphology. Gene detection shows amplification of MDM2 and EGFR gene. This tumor often has poor prognosis with aggressive behavior. Complete resection is the only effective therapeutic option. There is disagreement as to whether chemotherapy and radiotherapy can improve survival.

[Concordance of PD-L1 expression detected by two immunohistochemical platforms and antibodies].

Objective: To evaluate the concordance of PD-L1 expression in various tissues using antibodies 28-8 and SP263 on their respective detection platforms. Methods: Three hundred seventy four specimens of surgical resection of pulmonary diseases in the First Affiliated Hospital of Nanjing Medical University from January 1, 2012 to January 31, 2017 were collected. Totally 374 cases were tested for PD-L1 expression using the two antibodies, 28-8 and SP263, by respective detection platforms (Dako and Ventana). Finally, 336 cases were used for further evaluation, and the results were statistically analyzed for concordance. Results: For non-small cell lung carcinoma (NSCLC), the positive rate of PD-L1 was 57.5% (177/308) using SP263, and 57.5% (177/308) using 28-8 antibody. The correlation coefficient was 0.97 (P<0.01). The positive rate of both benign lung diseases and paracancerous tissues was about 10.7% (3/28), and the positive concordance rate was 100.0%. The distribution of both antibodies was also relatively consistent. Conclusions: The expression levels of 28-8 and SP263 antibodies in NSCLC and other tissues are relatively consistent, suggesting both antibodies may be complementary and substitute for each other, which may be useful in guiding clinical management.

Galanin receptor 1 plays an antinociceptive effect via inhibiting PKA activation in the nucleus accumbens of rats with neuropathic pain.

Galanin and galanin receptors (GalRs) have been reported to be involved in the transmission and modulation of nociceptive information in the central nervous system (CNS). However, the underlying mechanism of the antinociception of GalRs in neuropathic pain remains unclear. This study investigated the antinociception induced by galanin receptor 1 (GalR1) via protein kinase A (PKA) signaling pathway in the nucleus accumbens (NAc) of rats with neuropathic pain. A mononeuropathy model was replicated by ligation of the left sciatic nerve, following which the expression of phospho-PKA (p-PKA) in the NAc were markedly up-regulated at 14(th) and 28(th) day after ligation of sciatic nerve, and p-PKA expression was down-regulated by intra-NAc injection of GalR1 agonist M617, but the GalR1 antagonist M35 did not have an effect. We also found that M35 in the NAc blocked the M617-induced increase in the hind paw withdrawal latencies (HWLs) of rats with mononeuropathy, but M35 alone had no effect on HWLs, and PKA inhibitor H-89 attenuated the M617-induced an increase in the HWLs. These results suggested that GalR1 induced an antinociception via inhibiting PKA activation, implying that GalR agonists may be potential and potent therapeutic options to treat chronic neuropathic pain.

[Construction of chemical information database based on optical structure recognition technique].

OBJECTIVE: To create a protocol that could be used to construct chemical information database from scientific literature quickly and automatically. METHODS: Scientific literature, patents and technical reports from different chemical disciplines were collected and stored in PDF format as fundamental datasets. Chemical structures were transformed from published documents and images to machine-readable data by using the name conversion technology and optical structure recognition tool CLiDE. In the process of molecular structure information extraction, Markush structures were enumerated into well-defined monomer molecules by means of QueryTools in molecule editor ChemDraw. Document management software EndNote X8 was applied to acquire bibliographical references involving title, author, journal and year of publication. Text mining toolkit ChemDataExtractor was adopted to retrieve information that could be used to populate structured chemical database from figures, tables, and textual paragraphs. After this step, detailed manual revision and annotation were conducted in order to ensure the accuracy and completeness of the data. In addition to the literature data, computing simulation platform Pipeline Pilot 7.5 was utilized to calculate the physical and chemical properties and predict molecular attributes. Furthermore, open database ChEMBL was linked to fetch known bioactivities, such as indications and targets. After information extraction and data expansion, five separate metadata files were generated, including molecular structure data file, molecular information, bibliographical references, predictable attributes and known bioactivities. Canonical simplified molecular input line entry specification as primary key, metadata files were associated through common key nodes including molecular number and PDF number to construct an integrated chemical information database. RESULTS: A reasonable construction protocol of chemical information database was created successfully. A total of 174 research articles and 25 reviews published in Marine Drugs from January 2015 to June 2016 collected as essential data source, and an elementary marine natural product database named PKU-MNPD was built in accordance with this protocol, which contained 3 262 molecules and 19 821 records. CONCLUSION: This data aggregation protocol is of great help for the chemical information database construction in accuracy, comprehensiveness and efficiency based on original documents. The structured chemical information database can facilitate the access to medical intelligence and accelerate the transformation of scientific research achievements.

Liver Tissue-related Metabolic Mechanism of Different Infusion Volumes for Hemorrhagic Shock.

OBJECTIVES: To investigate the curative effects of various infusion volumes on liver-related metabolic mechanism in the treatment of hemorrhagic shock. METHODS: A severe hemorrhagic shock rabbit model was established in 30 rabbits. The rabbits were randomly divided into three groups： non-infusion group （A）, conventional infusion group （B）, and excessive infusion group （C） （n=10 in each group）. Taking group B as the control, groups A and C were observed for the damage of non-infusion and excessive infusion, respectively. The outcomes in the three groups and their relations with liver tissue metabolism changes were analyzed with gas chromatograph-mass spectrometer （GC-MS）. RESULTS: The mortality in groups A, B, and C group were 80%, 0%, and 70%, respectively. The liver tissue metabolic profile in group B showed statistically significant difference compared with that in groups A and B. In group C, the levels of 21 metabolites were lower than those in group B, and the levels of 8 metabolites were lower than those in group A. The relative contents of various metabolites were correlated with infusion volumes, and the succinic acid content was associated with death events （P<0.05）. CONCLUSIONS: The conventional infusion has significant curative effect on hemorrhagic shock. The metabolites of liver tissues with excessive infusion are generally decompensated and have longer survival time than those in non-infusion group, which may caused by the excessive infusion-induced blood volume increase after hemorrhagic shock. Tissue fluid dilution is an important cause of death.

Cortical response of the projected-thumb tactile sensation under TENS by MEG.

The existence of projected finger territories (PFTs) near the stump provides an essential way to realize the tactile sensation of lost fingers by transcutaneous electrical nerve stimulation (TENS). After amputation, the somatosensory cortex corresponding to lost fingers might be invaded by other cortical areas due to cortical plasticity. However, it was seldom observed how the amputees could feel the projected or lost finger tactile sensation in the cerebral cortex under TENS. To answer this question, by using magnetoencephalography (MEG), we investigated the cortical response under TENS of the projected thumb territory and normal thumb with 2 Hz current pulses. One subject with long-term left forearm amputation was recruited. The temporal and spatial characteristics of the activated cortical magnetic signals were analyzed. The Equivalent Current Dipoles (ECDs) corresponding to the strongest strength were mapped in the cerebral cortex, and the current density distribution were clearly illustrated. We found that the latencies at the maximum ECD strength were 60 ± 1.41 ms for the projected thumb and 46 ± 1.25 ms for the normal counterpart. The strongest ECD corresponding to projected thumb was located in the central sulcus near the mirror location of the normal thumb counterpart. And the response strengths of projected thumb cortex were stronger than normal thumb counterpart.

Association of genetic variations in the ACLY gene with growth traits in Chinese beef cattle.

ATP citrate lyase (ACLY) is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA, which is a key precursor of both fatty acid and mevalonate synthesis pathways. Genetic variation of the ACLY gene may influence multiple traits associated with animal production. Here, we identified three non-synonymous mutations in ACLY exons in five beef cattle populations using DNA pool sequencing and high-resolution melting analysis. Results from association analyses revealed that the single nucleotide polymorphism (SNP) g.17127C>T is significantly associated with chest girth (P < 0.01) and body height (P < 0.05) in the Fleckvieh x Zhangye local crossbred cattle, and with body slanting length (P < 0.05) in the Simmental x Guyuan local crossbred cattle. SNP g.40427T>C is significantly associated with an increase in chest girth (P < 0.05) in the Simmental x Huzhu cattle population. These results provide preliminary evidence that polymorphisms in the bovine ACLY gene are associated with growth traits in beef cattle in northwest China. However, a larger sample set is needed to validate these findings.

Germ cell-specific Atg7 knockout results in primary ovarian insufficiency in female mice.

Primary ovarian insufficiency (POI) is a common cause of infertility in around 1-2% of women aged <40 years. However, the mechanisms that cause POI are still poorly understood. Here we showed that germ cell-specific knockout of an essential autophagy induction gene Atg7 led to subfertility in female mice. The subfertility of Atg7 deletion females was caused by severe ovarian follicle loss, which is very similar to human POI patients. Further investigation revealed that germ cell-specific Atg7 knockout resulted in germ cell over-loss at the neonatal transition period. In addition, our in vitro studies also demonstrated that autophagy could protect oocytes from over-loss by apoptosis in neonatal ovaries under the starvation condition. Taken together, our results uncover a new role for autophagy in the regulation of ovarian primordial follicle reservation and hint that autophagy-related genes might be potential pathogenic genes to POI of women.

Feasibility of 2,4,6-trichlorophenol and malonic acid as metabolic uncoupler for sludge reduction in the sequence batch reactor for treating organic wastewater.

The activated sludge process generates a large amount of excess sludge as a byproduct, which is one of the most serious challenges in biological wastewater treatment. In the present study, the feasibility of 2,4,6-trichlorophenol (TCP) and malonic acid (MA) as metabolic uncouplers to reduce sludge generation in the sequence batch reactor (SBR) for treating organic wastewater for a long period was studied. The results showed that 2 mg/L TCP could reduce sludge generation by about 47%, while chemical oxygen demand (COD) removal efficiency and sludge settlability were not obviously influenced. Although 10 mg/L MA could also reduce excess sludge production by about 30% while slightly affecting COD removal, it seriously deteriorated sludge settlability. Accordingly, TCP is a better uncoupler for sludge reduction for a longer period in the SBR for treating organic wastewater, and MA can only be used as a short-term or transitional uncoupler. Microscopic and 16S ribosomal deoxyribonucleic acid analyses showed that the microbial population of sludge varied when uncouplers were fed to the activated sludge system. Occurrence of large amounts of filament and the disappearance of protozoa may be the main reason for the aggravation of sludge settlability under uncoupled metabolic conditions caused by MA.