Study on relationship of target organ injury of mechanism and "structure-effect-dose" of Hedysari Radix during radiotherapy-chemotherapy induced / 中国药理学通报

Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "

Research progress on material basis for neurotoxicity of traditional Chinese medicine and its mechanism / 中国药房

In recent years， neurotoxicity caused by traditional Chinese medicine （TCM） has frequently occurred and has become one of the important factors restricting the development and application of TCM. TCM contains active components and its dosage-effect relationship is the key to determine its pharmacological activity and toxic effects. Among them， the endogenous toxic components include alkaloids， glycosides， diterpenoids， animal and plant toxic proteins and heavy metals， and so on； exogenous toxic components mainly refer to some harmful elements and pesticide residues during the cultivation， processing， transportation and storage of medicinal materials that are not synthesized by themselves. Effect on the processes such as oxidative stress， inflammation， ion exchange， and energy metabolism may be important mechanisms of TCM-induced neurotoxicity. Neural cells， myelin cells， axons and neurotransmitter systems are common targets of TCM-induced neurotoxicity. In the future， we can use modern research methods and big data mining means to establish a safety evaluation mode of “toxic symptoms-poisoning dose-toxic original agent-detoxification scheme” with the basic component group of toxic substances as the core， so as to provide support for development and clinical intervention of neurotoxic traditional Chinese medicine.

Effect of electroacupuncture at different time points on postoperative urination function in patients with mixed hemorrhoids surgery / 中国针灸

OBJECTIVE@#To observe the effect of preoperative, intraoperative and postoperative electroacupuncture (EA) intervention on postoperative urination function in patients with mixed hemorrhoid surgery.@*METHODS@#A total of 240 patients with mixed hemorrhoid surgery under lumbar anesthesia were randomly divided into an EA preconditioning group (group A, 60 cases, 9 cases dropped off), an intraoperative EA group (group B, 60 cases, 4 cases dropped off), a postoperative EA group (group C, 60 cases, 6 cases dropped off), and a non-acupuncture group (group D, 60 cases, 3 cases dropped off). In the groups A, B and C, EA was exerted at Zhongliao (BL 33) and Huiyang (BL 35) , with disperse-dense wave, 4 Hz/20 Hz in frequency, and lasting 30 min, at 30 min before lumbar anesthesia, immediately after lumbar anesthesia and 6 h after surgery, respectively. No EA intervention was performed in the group D. The postoperative urination smoothness score in each group was observed 24 h after surgery. The first urination time, first urination volume, urine residual volume after first urination were recorded, and incidence of indwelling catheterization, postoperative visual analogue scale (VAS) score, number of remedial analgesia, and the incidence of postoperative nausea and vomiting were observed in each group.@*RESULTS@#In the groups A, B and C, the postoperative urination smoothness scores were superior to the group D (P<0.05), and the time of first urination was earlier than the group D (P<0.05). In the group C, the time of first urination was earlier than the group A and the group B (P<0.05), the first urination volume was higher than the group D (P<0.05), and the urine residual volume after first urination was lower than the group D (P<0.05). There was no significant difference in the incidence of indwelling catheterization and postoperative nausea and vomiting among the 4 groups (P>0.05). The VAS scores of the group A, B and C were lower than that in the group D (P<0.05), and the number of remedial analgesia cases was lower than that in the group D (P<0.05).@*CONCLUSION@#EA intervention could promote the recovery of urination function and relieve postoperative pain in patients with mixed hemorrhoids surgery. Early postoperative EA intervention is more conducive to the recovery of urination function.

Association between posterior tibial slope and tibial torsion angle and recurrent patellar dislocation based on the full-length CT of the lower limbs / 解剖学报

Objective To measure and compare the lateral posterior tibial slope (LPTS) , medial posterior tibial slope ( MPTS) and tibial torsion angle ( TTA) between the patients of recuiTent patellar dislocation and the heathy people, and to analyze the correlation between LPTS, MPTS and TTA and the risk factors of recuiTent patellar dislocation. Methods A total of 33 patients (44 knees) with recuiTent patellar dislocation in our hospital from July 2019 to June 2021 were selected and listed as the stud)' group. Twenty-three subjects (46 knees) who were suspected iliac vascular and lower limb vascular diseases during the same period were selected and listed as the control group. All the enrolled researchers had fulllength CT scans date of the lower limbs. Three-dimensional models were reconstructed using Mimics 21. 0 software and then imported into 3-matic software. The LPTS, MPTS and TTA were measured and compared between the two groups. Results In the study group, the LPTS, MPTS and TTA were (7. 69} 1. 42) ° , ( 10. 06} 1. 71) ° , ( 36. 42}8. 13 ) ° , respectively while the control group, the LPTS, MPTS and TTA were ( 8. 42 } 1. 65 ) ° , ( 10. 44 } 0. 86 ) ° , ( 25. 77} 3. 90 ) ° , respectively. There were no signiiicant differences in the LPTS, MPTS and TTA between different genders and sides both in the stud)' group and the control group ( P > 0. 0 5 ) . Compared with the control group, the LPTS in the stud)' group was smaller, and the difference was statistically significant (P0. 05). Compared with the control group, the TTA in the stud)' group was higher, and the difference was statistically significant (P< 0. 0 5 ) . Compared with the control group, the LPTS and MPTS in the study group were significant asymmetry, and the difference was statistically significant ( P < 0 . 0 5 ). Conclusion The lateral posterior tibial slope of patients with recurrent patellar dislocation is significantly smaller than that in the healthy people, while there is no significant difference in the medial posterior tibial slope; The tibial torsion angle of patients with recurrent patellar dislocation is significantly larger than in the healthy people; The lateral posterior tibial slope and tibial torsion angle have certain correlation with recurrent patellar dislocation, which can conduct the diagnosis of recurrent patellar dislocation.

Paeonol reduces microbial metabolite α-hydroxyisobutyric acid to alleviate the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in atherosclerosis mice / 中国天然药物

Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.

[Effect of fascia iliaca compartment block on anterolateral small incision total hip arthroplasty].

OBJECTIVE: To compare the effects of simple intraspinal anesthesia and combined fascia iliaca compartment block(FICB) on total hip arthroplasty(THA) through anterior lateral small incision (orthop dische chirurgie München, OCM). METHODS: From January 2019 to October 2020, patients undergoing unilateral total hip arthroplasty were treated with intraspinal anesthesia combined with ultrasound-guided fascia iliaca compartment block(30 cases in group A) and simple intraspinal anesthesia(30 cases in group B). Two groups were treated with the same intravenous analgesia after operation. The operation time, the amount of bleeding, the peeling degree of middle gluteal muscle, the splitting of greater trochanter of femur, the visual analysis scale (VAS) of hip joint after operation, the abductor muscle strength of quadriceps femoris and hip joint before and 48 hours after operation, and the Harris score of hip joint function after operation were observed and compared between two groups. RESULTS: All patients were followed up for 48 to 62 weeks with an average of (54.2±4.0) weeks. The incision length, operation time and intraoperative bleeding in group A were significantly lower than those in group B (P<0.05). The level of hemoglobin 24 hours after operation in group A was significantly higher than that in group B (P<0.05). The abductor muscle strength of hip joint in group A was significantly higher than that in group B 48 hours after operation (P<0.05). The degree of middle gluteal muscle dissection in group A was significantly lower than that in group B (P<0.05). The VAS of group A at 8, 12 and 24 hours after operation was significantly lower than that of group B (P<0.05);The Harris score in group A was significantly higher than that in group B at 2 and 8 weeks after operation (P<0.05). CONCLUSION: The application of ultrasound-guided fascia iliaca compartment block in lateral position OCM approach THA can significantly shorten the operation time, reduce the amount of bleeding, reduce the perihip trauma such as the peeling of middle gluteal muscle during operation, and improve the early postoperative pain of patients, which is conducive to the clinical operation of OCM approach and the rapid postoperative recovery of patients.

Clinical value of routine contrast esophagram in the diagnosis of anastomotic leakage for three-incision esophagectomy with cervical anastomosis / 中华外科杂志

Objective: To examine the clinical value of routine contrast esophagram (RCE) for the diagnosis of anastomotic leakage (AL) after three-incision esophagectomy with cervical anastomosis. Methods: Clinical data of 1 022 patients with esophageal cancer who underwent McKeown three-incision esophagectomy with cervical anastomosis from January 2015 to December 2019 at Department of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute were analyzed retrospectively. There were 876 males and 146 females, aging(M(IQR)) 48(16) years (range: 36 to 84 years). There were 253 patients (24.8%) with neoadjuvant therapy, and 817 patients (79.9%) with minimally invasive esophagectomy. According to the diagnosis and treatment habits of the attending surgeons, 333 patients were included in the RCE group, and RCE was performed on the 7th day postoperative, while 689 patients were included in the non-RCE group, and RCE was performed when the patients had suspicious symptoms. Taking clinical symptoms, RCE, CT, endoscopy and other methods as reference to the diagnosis of AL, the sensitivity and specificity were used to analyze and evaluate the efficacy of RCE for the diagnosis of AL. The data were compared by U test or χ² test between groups. Results: The incidence rate of AL after three-incision esophagectomy was 7.34% (75/1 022), including 30 cases in the RCE group and 45 cases in the non-RCE group (9.0%(30/333) vs. 6.5%(45/689), χ²=2.027, P=0.155). The diagnostic time of AL was 9(5) days postoperative (range: 4 to 30 days). Among them, 23 cases showed cervical leakages, 50 cases showed intro-thoracic leakages, and 2 cases both cervical and intro-thoracic leakages. The diagnostic time of patients with intro-thoracic leakages was longer than that of cervical leakages (10(4) days vs. 6(3) days, Z=-2.517, P=0.012). Among the 333 patients in the RCE group, 16 cases of RCE indicated leakages including 11 cases of true positive and 5 cases determined to be false positive, while 317 cases indicated no abnormalities including 19 cases developed leakages. The sensitivity and specificity of RCE to detect AL were 36.7%(11/30) and 98.3%(298/333), respectively. The Youden-index was 0.35, and the diagnostic accuracy was 92.8%(309/333). The positive and negative predictive value were 11/16 and 94.0%(298/317), respectively. Conclusions: Routine contrast esophagram after three-incision esophagectomy with cervical anastomosis has low sensitivity and high specificity in the diagnosis of AL. The diagnostic time of AL is the 9th day after surgery. It is necessary to prolong the observation time clinically, and combine RCE with CT, endoscopy and other inspection methods for diagnosis.

High-peak-power electro-optically Q-switched laser with a gradient-doped Nd:YAG crystal.

We report on a high-peak-power electro-optically Q-switched laser emitting a near-diffraction-limited beam profile at 1064 nm by using a gradient-doped Nd:YAG crystal. The gradient-doped crystal features a unique combination of a reduced thermal lens effect through effectively spreading the heat load distribution within its volume. Its performance is compared with those of Nd:YAG crystals with uniform volume doping distribution operating in the Q-switched regime with the same laser configuration, demonstrating the higher average and peak power achievable with the gradient-doped crystal. The maximum average output power amounts to 6.9 W at a pulse repetition rate of 2 kHz, which corresponds to a maximum peak power of ∼585kW. Compared to homogeneous dopant crystals, the slope efficiency and average output power increased by 30.8% and 21.1%, respectively.

Low microRNA150 expression is associated with activated carcinogenic pathways and a poor prognosis in patients with breast cancer.

Breast cancer is the most common type of cancer amongst women worldwide, and numerous microRNAs (miRNAs/miRs) are involved in the initiation and progression of breast cancer. The aim of the present study was to identify hub miRNAs and determine the underlying mechanisms regulated by these miRNAs in breast cancer. Breast invasive carcinoma transcriptome data (including mRNAs and miRNAs), and clinical data were acquired from The Cancer Genome Atlas database. Differential gene expression analysis, co­expression network analysis, gene set enrichment analysis (GSEA) and prognosis analysis were used to screen the hub miRNAs and explore their functions. Functional experiments were used to determine the underlying mechanisms of the hub miRNAs in breast cancer cells. The results revealed that low miR150 expression predicted a more advanced disease stage, and was associated with a less favorable prognosis. Through the combined use of five miRNA­target gene prediction tools, 31 potential miR150 target genes were identified. GSEA revealed that low miR150 expression was associated with the upregulation of several cancer­associated signaling pathways, and the downregulation of several tumor suppressor genes. Furthermore, miR150 independently affected overall survival in patients, and interacted with its target genes to indirectly affect overall and disease­free survival. Functional experiments demonstrated that miR150 positively regulated B and T lymphocyte attenuator (BTLA), and the downregulation of miR150 and BTLA combined promoted cell migration. In conclusion, the present study revealed that low miR150 expression was associated with less favorable clinical features, upregulation of several carcinogenic signaling pathways, and poor patient survival. Additionally, a miR150­BTLA axis was suggested to regulate cell viability and migration.

Study on alkaloid constituents of Stephania tetrandra S. Moore / 药学学报

Fifteen alkaloid compounds were isolated from the 70% aqueous alcohol extract of Stephania tetrandra S. Moore by silica gel, reversed phase silica gel, Sephadex LH-20 column chromatography and semi-preparative high performance liquid chromatography. They were identified as tetrandraside A (1), (Z)-N-formyl-nornuciferin (2), (E)-N-formyl-nornuciferin (3), salutaridine (4), salutaridine N-oxide (5), (E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2 propenamide (6), dauriporphine (7), sinomenine (8), liriodenine (9), α-magnoflorine (10), (1S)-4'-β-glucosylcoclaurine (11), tetrandrine (12), fangchinoline (13), tetrandrine 2'-β-oxide (14), and tetrandrine 2'-α-oxide (15), respectively, by MS, NMR and single crystal diffraction. Among them, compound 1 is a new alkaloid glycoside. Compounds 2-11 were obtained from this plant for the first time. These compounds showed obvious cytotoxic activity against drug-resistant lung cancer cell line H1299, and compound 9 had the best activity, with an IC50 of 5.38 μmol·L-1.

Effect of Trichosanthis Fructus-Allii Macrostemonis Bulbus on Formation of Atherosclerotic Plaque in ApoE-/- Mice Based on Autophagy of Vascular Smooth Muscle / 中国实验方剂学杂志

Objective:To explore the effect of Trichosanthis Fructus-Allii Macrostemonis Bulbus medicine on the proliferation and autophagy levels of aortic plaque vascular smooth muscle cells （VSMCs） in ApoE^-/- mice with atherosclerosis （AS）. Method:A total of 40 ApoE^-/- mice were fed with high-fat diet to replicate AS animal models. They were randomly divided into model group， Trichosanthis Fructus-Allii Macrostemonis Bulbus group， rapamycin group and atorvastatin group， and 10 mice with normal diet C57BL/6J mice were the blank group. The blank group and the model groups were given normal saline by gavage， while Trichosanthis Fructus-Allii Macrostemonis Bulbus group， rapamycin group and atorvastatin group were given corresponding drugs by gavage for 8 weeks. After the experiment， the mice were sacrificed. Total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） levels were detected by the Microplate reader， the ratio of the aortic plaque area to the total area was observed and measured by staining with aortic gross oil red O. Western blot method was used to detect the proliferation-related protein proliferating cell nuclear antigen （PCNA） and <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA） levels of VSMCs in the aortic media. Transmission electron microscopy was used to observe the autophagosomes of VSMCs and detect the expressions of VSMCs autophagy-related proteins Beclin-1， light chain proteinⅡ （LC3Ⅱ） and p62. Result:Compared with the model group， the Trichosanthis Fructus-Allii Macrostemonis Bulbus group showed significant reduction in the aortic lipid accumulation and plaque area of AS mice and the levels of TC， TG， LDL-C （<italic>P</italic><0.01） and increase of HDL-C （<italic>P</italic><0.05）. Trichosanthis Fructus-Allii Macrostemonis Bulbus significantly reduced the levels of proliferation-related antigens PCNA and <italic>α</italic>-SMA in aortic VSMCs （<italic>P</italic><0.01）， and inhibited the excessive proliferation of VSMCs. Trichosanthis Fructus-Allii Macrostemonis Bulbus significantly up-regulated Beclin-1 and LC3Ⅱ in aortic VSMCs protein expression， decreased p62 accumulation （<italic>P</italic><0.01）， increased the expressions of VSMCs autophagosomes， and increased the autophagy level of VSMCs. Conclusion:Trichosanthis Fructus-Allii Macrostemonis Bulbus regulates blood lipid levels in AS mice， and inhibits the excessive proliferation of aortic VSMCs and plaque formation in the aorta of AS mice. The mechanism may be related to the up-regulation of the autophagy activity of VSMCs.

Repeatability and Reliability of Home-Based Stool Color Card Screening for Biliary Atresia Based on Results in China and Japan.

Biliary atresia (BA) is the most frequent hepatic cause of death in early childhood. Early referral and timely Kasai portoenterostomy are essential for the improvement of long-term native liver survival rate of BA patients. Screening with stool color card (SCC) has been implemented in Japan since 1994. Recently current digital edition of SCC consisted of seven digitally created images was introduced to China. Our study aimed to evaluate the repeatability and reliability of same edition of SCC used in Beijing, China and Sapporo, Japan. In Beijing from 2013 to 2014, SCCs were distributed to infants' guardians by trained nurses in maternal facilities during information sessions on neonatal screening programs. SCC was used at three checkpoints for each infant after birth for screening. The SCC data were collected from 27,561 infants (92.5%) in Beijing by 42-day health checkup, mobile phone and social network services. In Sapporo from 2012 to 2015, the SCCs with a postcard and guardian instructions were inserted into Maternal and Child Health Handbook and distributed to all pregnant women. The data were collected from a total of 37,478 (94.3%) infants in Sapporo via the postcard during the 1st month infant health checkup. We thus identified two BA patients in Sapporo and two BA patients in Beijing. High rates of sensitivity and specificity in both cities were observed. The frequency distribution of color images on SCC reported in both cities was similar. This study shows excellent repeatability and reliability of the current digital edition of SCC.

Inborn errors of metabolism detectable by tandem mass spectrometry in Beijing.

Background Individual inborn errors of metabolism (IEMs) are rare disorders. Expanded newborn screening for IEMs by tandem mass spectrometry (TMS) is an efficient approach for early diagnosis. Here we provide the newborn screening program for the application of this approach (between July 2014 and March 2019) to the identification of newborns in Beijing at risk of developing a potentially fatal disease. Methods The amino acids and acylcarnitines in dried blood spots were analyzed by TMS. Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Results Among the healthy newborns, 16 metabolic disorder cases were confirmed, giving a total birth prevalence of 1:3666 live births. Organic acidemia (OA) was the most common (9/16 patients; 56%), and methylmalonic acidemia was the most frequently observed OA (7/9 patients; 89%). Five infants were diagnosed with methylmalonic acidemia with homocystinuria type CblC, two with isolated methylmalonic acidemia, one with propionic acidemia, and one with isovaleric acidemia. Four patients (4/16, 25%) were diagnosed with hyperphenylalaninemia. One suffered with medium-chain acyl CoA dehydrogenase deficiency, one with carnitine uptake deficiency, and one with citrin deficiency. Eleven cases underwent genetic analysis. Seventeen mutations in eight IEM-associated genes were identified in 11 confirmed cases. Symptoms were already present within 2 days after birth in 44% (7/16) cases. The infant with propionic acidemia died at 7 days after birth. The other cases received timely diagnosis and treatment, and most of them grew well. Conclusions The results illustrate challenges encountered in disease management highlighting the importance of newborn screening for inherited metabolic disorders, which is not yet nationally available in our country. Regional newborn screening programs will provide a better estimation of the incidence of IEM.

Paeonol inhibits macrophage M1 polarization by down-regulating miR-155/JAK1-STAT1 pathway / 中国中药杂志

The aim of this paper was to investigate the effect and mechanism of paeonol on peritoneal macrophage M1 polarization in mice, explore whether the intervention action is related to the down-regulation of miR-155 and the inhibition of downstream JAK1-STAT1 pathway, and provide a new idea for the molecular mechanism of paeonol against atherosclerosis(AS). Lipopolysaccharide(LPS) and interferon-γ(IFN-γ) were used to stimulate macrophages for 24 hours to establish the M1 polarization model, and paeonol was given 24 hours before co-stimulation to provide a pre-protective effect on cells. CCK-8 assay was used to detect the cells damage induced by LPS and IFN-γ co-stimulation; flow cytometry was used to detect the expression of M1 surface markers F4/80 and CD86. ELISA was used to detect the secretion of interleukin 6(IL-6) and tumor necrosis factor-α(TNF-α) in supernatant. RT-qPCR was used to detect the expression of miR-155, and Western blot was used to detect the protein expression at JAK1-STAT1-SOCS1 pathway. The results showed that LPS and IFN-γ had no obvious damage to the cells at the optimal concentration, but they induced macrophages polarized to M1, resulted in high expression of M1 type marker factors F4/80 and CD86 on the cell surface, and increased secretion of IL-6 and TNF-α on the cell surface(P<0.05 or P<0.01). Paeonol significantly reduced the LPS and IFN-γ-induced high expression of F4/80 and CD86, the secretion of inflammatory factors IL-6 and TNF-α(P<0.05 or P<0.01), decreased the expression level of miR-155, significantly down-regulated the protein phosphorylation level of JAK1-STAT1 and up-regulated the protein expression of SOCS1(P<0.01) in RAW264.7 cells. The results showed that paeonol could inhibit M1 polarization of macrophages by down-regulating cell surface marker factors and inflammatory factors secreted by cells, which may be related to the down-regulation of miR-155 expression and the inhibition JAK1-STAT1 pathway activation.

Molecular identification of Tricula spp. and the parasitized trematode cercariae in schistosomiasis-endemic areas of Yunnan Province / 中国血吸虫病防治杂志

Objective To characterize a species of the genus Tricula and parasitized trematodes in schistosomiasis-endemic areas of Yunnan Province using a molecular analysis, so as to understand their taxonomic positions. Methods Tricula spp. and Oncomelania snails were collected from Xiangyun County, Yunnan Province, and cercaria parasitizing snails were observed using crushing followed by microscopy. Cercaria parasitizing Tricula snails at various morphologies were sampled using a shedding method. Genomic DNA was extracted from snail soft tissues and cercariae, and the 16S rRNA, COI, 28S rDNA genes in snails and the ND1 and 28S rDNA genes in cercariae were amplified using a PCR assay and sequenced. The species of Tricula snails and their parasitized trematodes was characterized using sequence alignment and phylogenetic analysis. Results Among 382 Tricula snails detected, there were three types of trematode cercariae found, including the non-forked (20.94%, 80/382), double-forked (3.40%, 13/382) and swallow shapes (7.07%, 27/382). Sequence and phylogenetic analyses showed that the 16S rRNA, COI and 28S rDNA gene sequences of this species of Tricula had high homology to those in Delavaya dianchiensis, and were clustered in a branch. Sequencing analysis of the ND1 and 28S rDNA genes revealed that the non-forked cercariae belonged to the family Pleu- rogenidae, the swallow-shaped cercariae belonged to the family Opecoelidae, and the double-forked cercariae belonged to another species of the genus Schistosoma that was different from S. sinensium and S. ovuncatum. Conclusion The species and taxonomy of Triculla spp. and their parasitized trematodes are preliminarily determined in schistosomiasis-endemic areas of Yunnan Province; however, further studies are required to investigate the more definite taxonomy and pathogenicity.

A pilot study on newborn screening for congenital adrenal hyperplasia in Beijing.

Background A provisionary screening programme for 21-hydroxylase deficiency (21-OHD) was initiated in Beijing in 2014. The aim of this study was to investigate the incidence and the associated clinical characteristics of neonatal congenital adrenal hyperplasia (CAH) in Beijing and to provide evidence-based guidance for its application in CAH screening. Methods Live birth newborns (n=44,360) were screened for CAH in Beijing from July 2014 to April 2018. The levels of 17-hydroxyprogesterone (17-OHP) in the blood were estimated using the time-resolved fluoroimmunoassay. Neonates with a positive result and a level >30 nmol/L of 17-OHP were called for a retest. CAH was diagnosed based on further laboratory findings combined with clinical signs, such as weight loss, feeding difficulties, skin pigmentation, and atypical genitalia. Through a review of medical records, the clinical findings including molecular data were reported. Results Of the 44,360 neonates screened, 280 cases were deemed positive. Of these, 203 neonates were recalled for further tests and six patients (three boys and three girls) were diagnosed with CAH. Five cases of classic salt-wasting and one case of simple virilising 21-OHD were identified. The incidence of CAH in Beijing was 1:7393. The most frequent 21-OHD mutation was c.293-13C/A>G. Conclusions The incidence of CAH in Beijing was higher than the national average. The results support the need for neonatal CAH screening in Beijing. This pilot study demonstrates the clinical characteristics of 21-OHD through newborn screening. Early detection and treatment through neonatal screening may reduce mortality rates and optimise developmental outcomes.

Whole-exome sequencing as a powerful tool for identifying genetic causes in a patient with POLG-related disorders and phenylketonuria.

OBJECTIVE: This study's aim was to identify the genetic causes in a patient with phenylketonuria and hearing loss, liver disease, developmental and mental retardation, hypotonia, and external ophthalmoplegia. METHODS: Whole-exome sequencing and Sanger sequencing analysis were used to determine the genetic causes of manifestations in a young boy with hearing loss, liver disease, develop-mental and mental retardation, hypotonia, and external ophthalmoplegia. RESULTS: We found that the child harbored polymerase gamma ( POLG) compound heterozygous mutations, c.2617G>A (p.E873K) and c.3550G>A (p.D1184N), and phenylalanine hydroxylase ( PAH) compound heterozygous mutations, c.721C>T (p.R241C) and c.728G>A (p.R243Q). Among them, the POLG p.E873K mutation is a novel mutation and is not present in the Exome Aggregation Consortium database, Genome Aggregation database, and 1000 Genomes database. The two heterozygous mutations were each inherited from both of the child's parents. This finding suggested that the phenotype and the genotype were segregated. CONCLUSION: Using whole-exome sequencing, we not only identified PAH mutations causing phenylketonuria, but also identified the genetic cause of the mitochondrial disease and found a novel POLG mutation. Our findings could be useful in helping future parents obtain healthy embryos through assisted reproductive technology.

[Radiological study on the cup abduction angle during total hip arthroplasty].

OBJECTIVE: To analyze the relationship among the parameters by measuring the relevant parameters of the anteroposterior X-ray of both hips in patients after total hip arthroplasty, to discuss the reliable anatomical markers and reference standards of acetabulum placement in total hip arthroplasty, and finally to accurately control the abduction angle of acetabulum. METHODS: From January 2016 to June 2017, 282 patients (235 hips) underwent total hip arthroplasty and 128 patients(157 hips) met the inclusion criteria. There were 91 males and 37 females, 82 cases of the left hip and 75 cases of the right hip; ranging in age from 22 to 78 years old, with a mean of 55.1 years old. The abduction angle(ß), ilium thickness (a), acetabular cup insertion depth (b), ischial thickness (c), acetabular cup insertion depth(d), acetabular abrasion and contusion depth(e) were measured on the postoperative AP X-ray of both hips, and the data were compared. RESULTS: There was a positive correlation between ß and b (r=0.424, P=0.000), a negative correlation between ß and d (r=-0.407, P=0.000), a positive correlation between ß and b/a (r=0.419, P=0.000), a negative correlation between ß and d/c (r=-0.472, P=0.000). There was a linear relationship between ß and b/a (t=5.753, P=0.000) and a linear relationship between ß and d/c (t=-6.671, P=0.000). CONCLUSIONS: The outreach angle is mainly controlled by the distance between the outer edge of the cup and the outer edge of the cup in the inferior portion(d) during the operation. The distance b from the outer edge of the cup can be used as a reference.

The Impact of Gene Polymorphisms on Anticoagulation Control With Warfarin.

Differences in warfarin maintenance dosages based on the presence of polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through dosage adjustment according to routine guidelines. Little is known about whether routine therapy could provide consensus anticoagulation control for patients with different genotypes. This study was carried out to compare anticoagulant control in patients with different genotypes. Six hundred seventy patients using warfarin according to Chinese guidelines were enrolled. Warfarin dosages and monitored international normalized ratios (INRs) were recorded. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622, CYP2C9 rs1057910, and ORM1 rs17650 polymorphisms were determined. Warfarin dosages and INR were compared between genotypes. Patients with the AGCC*F*F*1*1 polymorphism took longer than patients with the AACC*F*F*1*1 polymorphism (20 vs 5 days, P < .001) to achieve the targeted INR range. The INR values of patients with AACC*F*F*1*3 were unstable and did not enter the stable state control phase until after 35 days. The peak INR of patients with the AACC*F*F*1*3 polymorphism was exceedingly high, with some values exceeding the control range limit of 3.0. Patients with the AACC*F*S*1*1 or AACT*F*F*1*1 polymorphisms exhibited similar INR values as the patients with the AACC*F*F*1*1 polymorphism. This study found that routine medication with warfarin provides significantly different levels of anticoagulant control between patients with wild-type genotypes and patients with heterozygous polymorphism genotypes of VKORC1 rs9923231 or CYP2C9 rs1057910. Patients with heterozygous polymorphism genotypes of VKORC1 or CYP2C9 require genotype-directed therapy with warfarin to increase efficacy and safety in anticoagulant treatment.

Expression and Clinical Significance of mPGES-1 and NF-κB p65 in Diffuse Large B Cell Lymphoma / 中山大学学报(医学科学版)

[Objective]Examine the expression of microsomal prostaglandin E synthase-1(mPGES-1)and nuclear transcription factor kappa B p65(NF-κB p65)in diffuse large B cell lymphoma(DLBCL),assessing their correlation with clinical variables,prognosis and potential clinical valve.[Methods]The immunohistochemistry was uesd to investigate the expression of mPGES-1 and NF-κB p65 in 83 DLBCL patiens'tissues.The relationship between these two proteins and the clinical variables and prognosis of these patients was evaluated.[Results]The high expression of mPGES-1 and NF-κB p65 were observed in 65.1%(54/83)and 73.5%(61/83)cases of DLBCL,respectively.The expression level of NF-κB p65 was positively correlated with mPGES-1 expression(P<0.05).The expression of these two proteins was found to be significantly associated with B cell lymphoma/leukemia-2 protein(BCL-2),higher expression of Ki67,higher lactate dehydrogenase (LDH),more extranodal lesions,advanced Ann Arbor stage and higher international prognostic index(IPI)score(P<0.05). In addition,NF-κB p65 was related with multiple myeloma oncogene 1(MUM1),pathological type(P<0.05). Both mPGES-1 and NF-κB p65 overexpression was correlated with worse overall survival(OS)while NF-κB p65 was an in-dependent prognostic factor for OS of DLBCL(P<0.05).[Conclusions]mPGES-1 and NF-κB p65 were highly expressed in DLBCL and closely linked with each other. The overexpression of mPGES-1 and NF-κB p65 was correlated with tumor progression and unfavorable prognosis in patients with DLBCL.