Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center / 中华妇产科杂志

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.

Changes of macular retinal structure and microcirculation in patients with pituitary adenoma observed by optical coherence tomography and optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the changes of macular retinal structure and microcirculation in patients with pituitary adenoma(PA)by optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 40 PA patients treated at the department of neurosurgery, Affiliated Hospital of Guangdong Medical University from September 2021 to March 2023 were included as PA group, and 42 age- and gender-matched healthy volunteers were selected as normal control group. All patients underwent visual field, OCT and OCTA examinations, and the correlation of ocular parameters in PA patients was analyzed.RESULTS:The vessel density(VD)of each retinal layer in the macular area of the PA group was lower than that of the normal control group, and the superficial vascular complex(SVC)-VD in the macular area was positively correlated with the thickness of the macular ganglion cell complex(mGCC)(except the nasal side of the inner ring and the lower part of the outer ring; P<0.05). The thickness of mGCC in each quadrant of the macular area and the thickness of the circumpapillary retinal nerve fiber layer(CP-RNFL)in each quadrant were negatively correlated with the mean defect(MD)value of the visual field(P<0.05), and the area of the foveal avascular zone(FAZ)was positively correlated with the MD value(P<0.05).CONCLUSION:The combination of OCT and OCTA can fully understand the microscopic changes of retinal structure and microcirculation function in PA patients, which is of great value in evaluating the preoperative visual function of PA patients.

Prenatal Diagnosis of 18q Deletion Syndrome / 中山大学学报(医学科学版)

ObjectiveTo explore the prenatal diagnostic methods of 18q deletion syndrome and improve understanding on the value of non-invasive prenatal testing （NIPT） in prenatal diagnosis of 18q deletion syndrome. Methods18q deletion syndrome was detected by conventional methods such as serological screening， ultrasonic imaging examination， chromosome karyotype analyses of both amniotic fluid cells and parental peripheral blood， and molecular biological techniques including NIPT， chromosomal microarray analysis （CMA） and copy number variation sequencing （CNV-Seq）. Genetic counseling was conducted based on these examination results. ResultsNIPT identified a 24 MB deletion on the chromosome 18 which contained 17 genes including BCL2 by karyotype analysis of amniotic fluid cells and CMA. Further ultrasonic imaging examination confirmed the diagnosis of 18q deletion syndrome and karyotype analysis of parental peripheral blood revealed a de novo deletion mutation. ConclusionsInterventional prenatal diagnosis is an integral standard for the diagnosis of 18q deletion syndrome. NIPT， as an important screening test in middle pregnancy， can indicate the early possible chromosome segment deletion and reduce the time and economic cost when no abnormality is found in ultrasonic imaging.

“Liquid seal to detoxification – drying and puffing” of two stage processing technology design and pharmacodynamic study of aconite (Aconiti Lateralis Radix Praeparata) processed by microwave / 药学学报

Establish a production line with controllable process and high intelligence, contribute to improve the quality and production efficiency of aconite processed by microwave, and promote the transformation and application of aconite processed by microwave. According to the principle of aconite detoxification and the characteristics of industrial microwave equipment, an industrial production line of aconite processed by microwave was established with diester alkaloids and monoester alkaloids as indicators, and pilot production was carried out. At the same time, the content of active constituents and efficacy were compared with that of the main processed products, such as Shengfupian, Baifupian and Heishunpian. The results showed that the industrial production of aconite processed by microwave can be divided into two stages: "Liquid seal to detoxification - drying and puffing". The content of monoester alkaloids in 10 batches of aconite processed by microwave was 0.071%-0.166% and the content of diester alkaloids was 0.004%-0.016%, which met the relevant requirements of the Chinese Pharmacopoeia in 2020. Compared with Heishunpian and Baifupian, the retention rate of the effective components of aconite processed by microwave was higher. Pharmacological experiments showed that aconite processed by microwave not only retained the anti-inflammatory and analgesic activities of Heishunpian and Baifupian, but also significantly increased the levels of leukocytes and lymphocytes in mice with liver cancer chemotherapy, enhanced the CD4/CD8 ratio in spleen cells of mice (P < 0.05), thus regulating the body's immunity. However, this effect of Baifupian was weak, while Heishunpian and Shengfupian had no such effect. Through the above research, this study established microwave processing line with controllable process and high intelligence, as well produced the aconite processed by microwave with low toxicity and stable quality. It laid a foundation for the industrialized continuous production and clinical positioning of aconite by microwave processed, and provided scientific support for the development and application of microwave technology in the field of traditional Chinese medicine. All animal experiments in this study were reviewed and approved by the Experimental Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine before being carried out (Approval No. 2020-28).

Analysis on health status and influencing factors of 1353 mercury workers in Xinjiang / 中华劳动卫生职业病杂志

Objective: To investigate the health status of workers exposed to occupational mercury, and to provide the theoretical basis for formulating reasonable health monitoring and targeted protection measures. Methods: In November 2021, 1353 mercury-exposed workers who underwent occupational health examination in a hospital in Xinjiang Uygur Autonomous Region from 2018 to 2021 were collected as research subjects. By analyzing their blood pressure, electrocardiogram, blood routine, liver function and urine β2-microglobulin and urinary mercury in different gender, age, length of service, industry and enterprise scale, and the health status. And the influencing factors of urinary mercury were evaluated. Results: Among 1353 workers exposed to mercury, there were 1002 males (74.1%), the average age was (37.2±9.8) years old, and the length of service was 3.1 (2.0, 8.0) years. The abnormal rates of physical examination, blood pressure, electrocardiogram, blood routine, liver function, urinary β2-microglobulin and urinary mercury were 73.9% (1000/1353), 12.3% (166/1353), 30.2% (408/1353), 59.9% (810/1353), 32.5% (440/1353), 15.2% (205/1353) and 2.2% (30/1353), respectively. The abnormal rates of blood pressure, blood routine, liver function, urinary β2-microglobulin and urinary mercury in male workers were higher than those in female workers (P<0.05). The abnormal rates of workers' blood pressure and physical examination results increased with the increase of age and length of service, while the abnormal rate of electrocardiogram results were opposite (P<0.05). There were statistically significant differences in the abnormal rates of blood pressure, blood routine, urinary β2-microglobulin and physical examination results among workers of different enterprises and different industries (P<0.05). Multivariate logistic regression analysis showed that the workers with age ≥30 years old, microminiature enterprises, abnormal physical examination results and urinary β2-microglobulin were the susceptible population with abnormal urinary mercury (P<0.05) . Conclusion: The occupational health status of mercury workers in Xinjiang Uygur Autonomous Region is not optimistic, and the health monitoring of microminiature enterprises and older workers should be improved to effectively protect the physical and mental health of workers.

Plastic and reconstruction surgery for non-healing wound after posterior spinal surgery / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical significance of different plastic surgeries in the treatment of poor healing wound after posterior spinal internal fixation.@*METHODS@#In this study, 16 patients with poor incision healing after posterior spinal internal fixation were retrospectively included, and dif-ferent plastic surgery treatment plans were determined according to the wound characteristics and defect condition. The measures included debridement, vacuum sealing drainage (VSD), and different tissue flaps according to the location and extent of the defect.@*RESULTS@#A total of 16 patients meeting the criteria were included, of whom 3 were treated with debridement combined with VSD and wound suture directly, 6 were treated with debridement combined with Z-flap for wound repair, 1 was treated with bilateral sacrospinous muscle flap for dural defect repair combined with Z-flap for skin wound repair, 1 was treated with lectus dorsi flap for wound repair, 3 were treated with the fourth lumbar artery perforator flap for wound repair. The wound was repaired with local rotating flap in 1 case and gluteus maximus musculocutaneous flap in 1 case. Among the 16 patients, 7 cases were positive for wound culture, including 3 cases of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa, 1 case of Staphylococcus epidermidis, 1 case of Escherichia coli, 1 case of Klebsiella pneumoniae, and the other 9 cases were negative. After surgery, there were 7 patients with different degrees of poor wound healing, including 3 patients undergoing dressing change, 2 patients undergoing secondary debridement and suture, 1 patient undergoing free scalp skin graft, and 1 patient undergoing local effusion suction treatment. All the above 7 patients were discharged from hospital after improvement, and the remaining 9 patients had good first-stage wound hea-ling after surgery. None of the 16 patients underwent internal fixation.@*CONCLUSION@#Multiple factors could lead to poor wound healing after posterior spinal internal fixation. Early intervention, thorough debridement, removal of necrotic/infected tissue, and selection of suitable skin flap for effective wound fil-ling and covering were important means to ensure wound healing after spinal surgery and reduce removal of internal fixation.

Technical guideline for school sanitary and anti epidemic measures after flood disasters / 中国学校卫生

Abstract@#Flood disasters are the common public health emergencies, mainly leading to environmental damage, water pollution, food pollution, vector breeding, infectious disease epidemic and other risk factors of sanitary and anti epidemic work. The guideline has been formulated with reference to the technical documents such as Guideline for Environmental Sanitation Disposal and Preventive Disinfection in Flooded Areas and Technical Proposal for Sanitary and Anti epidemic Measures after Flood Disasters, as well as the latest research progress at home and abroad. In order to guide the sanitary and anti epidemic measures in flooded areas, protect the health and safety of students and teachers and ensure the normal educational and teaching order, the guideline introduces the key measures that should be taken by schools, teachers and students in flood striken areas.

Mechanism and clinical value of long non-coding RNA in the development of atherosclerosis / 中华检验医学杂志

Long non-coding RNAs (lncRNA) are a class of non-coding RNA with a length of more than 200 nucleotide, it is known that lncRNA can regulate gene expression at epigenetic, transcriptional and post transcriptional levels. Recent studies have shown that lncRNA is an important regulator of atherosclerosis (AS) and plays an important role in the pathogenesis of AS. This paper aims to comprehensively explore the mechanism of lncRNA in AS and summarize new biomarkers for AS diagnosis, we focused on the research progress of some key lncRNA in regulating the function of endothelial cells, smooth muscle cells, and monocytes and macrophages through literature review. Furthermore, this review discusses the potential clinical diagnostic value of lncRNA as biomarker in coronary heart disease (CHD), acute myocardial infarction, and heart failure (HF). LncRNA is expected to become a new class of clinically relevant biomarker, which might be useful for the prediction, diagnosis, prognosis and risk stratification of AS and cardiovascular diseases.

Combining vibroacoustic therapy with audio-visual feedback can improve the swallowing and the emotional state of survivors of a brainstem stroke / 中华物理医学与康复杂志

Objective:To observe any effect of combining vibroacoustic therapy with audio-visual feedback on the swallowing and the emotional state of persons with a swallowing disorder after a brainstem stroke.Methods:Fifty brainstem stroke survivors with dysphagia were randomly divided into a control group and a combination group, each of 25. In addition to routine swallowing function training, the control group received additional direct feeding training, while the combination group was provided with vibroacoustic feeding training and swallowing stimulation from an animated audio-visual presentation. Before and after the treatment, the subjects′ swallowing function was quantified using the Standard Swallowing Assessment (SSA) scale and the Gugging swallowing screen (GUSS). The Positive and Negative Emotions Scale (PNAS) was used to quantify their emotional state.Results:After the treatment the average SSA scores of both groups had decreased significantly, while the average GUSS and PNAS scores had increased significantly. The average improvements in all three measures were significantly greater in the combination group than in the control group.Conclusion:In addition to routine swallowing function training, feeding training applying vibroacoustics and audio-visual stimulation can significantly improve the feeding function and emotional state of brainstem stroke survivors with dysphagia.

The effects on the language ability and life quality of aphasic stroke survivors of synchronous, long-distance speech rehabilitation training based on Oral Reading for Language with Aphasia / 中华物理医学与康复杂志

Objective:To observe any effect of long-distance application of Oral Reading for Language with Aphasia (ORLA) training on patients with post-stroke aphasia.Methods:A total of 42 stroke survivors with aphasia were randomly divided into an inpatient group, and two online groups, each of 14. All three groups had their routine rehabilitation treatment supplemented with ordinary multimodal language therapy and ORLA. The inpatient group completed the routine in the rehabilitation treatment room, while the online groups completed it at home using Tencent video conferencing software. The conventional multimodal language therapy was conducted once daily, 5 days a week for 4 weeks. For the inpatient group and online group 2 the daily session lasted 30 minutes, while for the online 1 groups the daily length was doubled. The ORLA therapy was also conducted once daily, 5 days a week for 4 weeks, for the inpatient group and online group 2 the daily session lasted 1h, while for the online 1 groups the daily length was 30min.The speech function, reading ability and life quality of the three groups were evaluated before and after the intervention using the Western Aphasia Battery, the Chinese Standard Aphasia Examination Scale and the Chinese version of the Stroke Aphasia Quality of Life Scale.Results:After treatment, the average aphasia quotient (AQ), reading, naming and quality of life scores in all three groups had improved significantly compared with those before treatment. And related language ability scores (such as retelling, fluency, information volume, listening comprehension, etc.) had also improved significantly in all three groups. However, the average AQ, reading, and oral fluency scores of the inpatient group and online group 2 were significantly higher than those of online group 1. Significant improvement was also observed in the reading aloud and life quality of all three groups, but the average improvement in reading aloud was significantly greater in the inpatient group and in online group 2 compared to online group 1. The average life quality of the online groups was significantly superior to that of the inpatient group.Conclusion:Medium- and high-intensity ORLA synchronous remote speech rehabilitation can significantly improve the speech ability, reading ability and life quality of aphasic stroke survivors.

Effect of superior cervical ganglion block on cardiac function and NLRP3 signaling pathway in a rat model of myocardial ischemia-reperfusion / 中华麻醉学杂志

Objective:To evaluate the effect of superior cervical ganglion block (SCGB) on cardiac function and nucleotide like receptor protein 3 (NLRP3) signaling pathway in a rat model of myocardial ischemia-reperfusion (I/R).Methods:Sixty healthy SPF male Sprague-Dawley rats, weighing 250-300 g, aged 2-3 months, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (sham group), myocardial I/R group (IR group), myocardial I/R + normal saline group (IR+ NS group), and myocardial I/R + SCGB group (IR+ SCGB group). Myocardial I/R model was developed by ligation of the left anterior descending branch of the coronary artery for 45 min followed by restoration of blood flow in anesthetized aninals. IR+ SCGB group received SCGB (0.25% ropivacaine 0.1 ml) at 10 min before reperfusion once a day for 2 consecutive weeks, while 0.9% sodium chloride was given instead of ropivacaine in IR+ NS group. Blood samples were collected at 24 h and 14 days of reperfusion for determination of serum concentrations of norepinephrine (NE), troponin T (TnT), tumor necrosis factor-alpha (TNF-α), interleukin-18 (IL-18) and IL-1β by enzyme-linked immunosorbent assay. Echocardiography was performed before ischemia and at 14 days of reperfusion, and left ventricular short axis shortening rate (FS), ejection fraction (EF), and cardiac output (CO) were measured. The rats were sacrificed at 14 days of reperfusion and the hearts were taken for determination of the contents of norepinephrine (NE) in myocardial tissues in the infarction area (by enzyme-linked immunosorbent assay), percentage of myocardial fibrosis area (by Masson staining), M1 macrophage marker CD68 + cell count in the infarction area (by immunohistochemical method), and expression of NLRP3 and gasdermin D (GSDMD) in myocardial tissues (by Western blot). Results:Compared with Sham group, the serum concentrations of TnT, TNF-α, IL-18 and IL-1β, percentage of myocardial fibrosis area, and NE levels in serum and myocardial tissues were significantly increased, the expression of NLRP3 and GSDMD in myocardial tissues was up-regulated, CD68 + cell count was increased, and EF, CO and FS were decreased in IR group ( P<0.05). Compared with IR group, the serum concentrations of TnT, TNF-α, IL-18 and IL-1β, percentage of myocardial fibrosis area, and NE levels in serum and myocardial tissues were significantly decreased, the expression of NLRP3 and GSDMD in myocardial tissues was down-regulated, CD68 + cell count was decreased, and EF, CO and FS were increased in IR+ SCGB group ( P<0.05), and no statistically significant changes were found in the parameters mentioned above in IR+ NS group ( P>0.05). Conclusions:SCGB can improve the cardiac function in a rat model of myocardial I/R, and the mechanism may be related to the inhibition of NLRP3 signaling pathway.

Research progress on the application of hydrogel spacer in brachytherapy for gynecological tumors / 中华放射肿瘤学杂志

Radiotherapy is an important treatment of gynecological tumors. Although novel techniques or measures in recemy years have improved the tumor control rate and reduced radiation toxicity, radiation toxicity remains a major problem due to the location of some key organs adjacent to the tumor. A new material-hydrogel, as an organ spacer, provides a new method to reduce the radiotherapy toxicity. In this article, the application of hydrogel as an organ spacer in brachytherapy for gynecological tumors was reviewed from the aspects of hydrogel characteristics, suitable population, mode of injection, interval distance and dose effect, clinical benefits and cost effectiveness, etc.

Analysis of the rectum and bladder changes in prostate precise radiotherapy under the bowel and bladder preparation / 中华放射肿瘤学杂志

Objective:To analyze the clinically acceptable and reproducible bladder and rectum volumes of prostate cancer patients during radiotherapy under bladder and bowel preparation, aiming to provide quantitative indicators for bowel and bladder preparation before and after radiotherapy.Methods:Clinical data of 275 prostate cancer patients with strict bladder and bowel preparation and completion of whole course radical radiotherapy at Sun Yat-sen University Cancer Center from April 2015 to December 2020 were retrospectively analyzed. Patients were scanned with cone beam CT (CBCT) before each treatment and the setup error was recorded. Sixty-six patients were selected by simple random sampling and the bladder and rectum on daily CBCT was outlined using MIM software. The relationship between the ratio of daily bladder or rectum volume to the planned bladder or rectum volume (relative value of volume) and setup error was analyzed. Quantitative data were expressed as mean±SD. Normally distributed data were analyzed by paired t-test while non-normally distributed data were assessed by Kruskal-Wallis test.Results:The bladder and rectum volume on planning CT were (370.87±110.04) ml and (59.94±25.07) ml of 275 patients. The bladder and rectum volumes on planning CT were (357.51±107.38) ml and (65.28±35.37) ml respectively of the 66 selected patients with 1611 sets of CBCT images. And the bladder and rectum volumes on daily CBCT were (258.96±120.23) ml and (59.95 ± 30.40) ml. The bladder volume of patients was decreased by 3.59 ml per day on average during the treatment and 0.37 ml for the rectum volume. According to the bladder volume on planning CT, all patients were divided into three groups: <250 ml, 250-450 ml and >450 ml groups. The relative value of volume in the 250-450 ml group during the course of radiotherapy was the smallest. And the setup error in the superior and inferior (SI) direction was (0.28±0.24) cm and (0.19±0.17) cm in the left and right (LR) direction, significantly lower than those in the other two groups (both P≤0.027). According to the rectum volume on planning CT, all patients were divided into four groups: <50 ml, 50-<80 ml, 80-120 ml and >120 ml groups. The <50 ml group had the smallest relative value of volume during radiotherapy, and the setup error in the SI direction was (0.26±0.22) cm and (0.24±0.22) cm in the anterior and posterior (AP) direction, significantly smaller than those in the other groups (both P≤0.003). The setup errors in the SI, LR, AP directions of the enrolled 66 patients were (0.30±0.25) cm, (0.20±0.18) cm and (0.28±0.27) cm, respectively. Among them, the relative value of bladder volume in the AP direction was (0.73±0.37) in the setup error <0.3 cm group, which was statistically different from those in the setup error 0.3-0.5 cm and >0.5 cm groups (both P<0.05). Conclusion:Under the bladder and bowel preparation before planning CT, the appropriate bladder and rectum volumes are in the range of 250-450 ml and <50 ml, which yields higher reproducibility and smaller setup error.

Analysis of the current status and influencing factors of physical activity, sedentary behavior in middle-aged and elderly patients with stable coronary heart disease / 中国实用护理杂志

Objective:To explore the status and influencing factors of physical activity, sedentary behavior in middle-aged and elderly patients with stable coronary heart disease, and to provide reference for clinical medical staff to formulate targeted intervention measures.Methods:This was a cross-sectional survey. From March to June 2022, a convenience sampling was used to select 378 middle-aged and elderly patients with stable coronary heart disease in the ward and clinic of Department of Cardiology, Jinshan Hospital, Fudan University. The general information questionnaire, the International Physical Activity Questionnaire, the Adult Sedentary Behavior Questionnaire, the Tampa Scale for Kinesiophobia Heart, the Self-efficacy for Chronic Disease Scale and the Social Support Rating Scale were used for investigation.Results:The total metabolic equivalent of physical activity and sedentary time in middle-aged and elderly patients with stable coronary heart disease were 31.40 (21.73, 49.67) MET-h/w and 8(7, 9) h/d respectively. The 39.7% (150/378) patients reached physical activity guidelines recommendations and 61.4% (232/378) patients had a sedentary time ≥ 8 h/d. The 19.0% (72/378) patients were identified as physically active/low sedentary group, 20.6% (78/378) patients were identified as physically active/high sedentary group, 19.6% (74/378) patients were in physically inactive/low sedentary group and 40.7% (154/378) patients were in physically inactive/high sedentary group. The stepwise multiple regression analysis showed that sedentary behavior, working status, kinesiophobia, objective support and disease duration had significant impacts on physical activity ( t values were -9.81-2.67, all P<0.05). The influencing factors of sedentary behavior were physical activity, objective support, support utilization, gender, educational level and kinesiophobia ( t values were -10.77-4.63, all P<0.05). Conclusions:The status of physical activity, sedentary behavior in middle-aged and elderly patients with stable coronary heart disease is not good. Medical staff should intervene corresponding influencing factors to reduce the risk of physical inactivity and high sedentary behavior in this group.

Newborn screening for ornithine transcarbamylase deficiency in Zhejiang Province and the follow-up analysis / 中华实用儿科临床杂志

Objective:To investigate the incidence, clinical characteristics and prognosis of ornithine transcarbamylase deficiency(OCTD) in newborns in Zhejiang Province.Methods:A retrospective research was conducted.A total of 4 261 036 newborns from Department of Genetics and Metabolism, Children′s Hospital, Zhejiang University School of Medicine, between January 2009 and December 2021 were screened for inherited metabolic disorders using tandem mass spectrometry.OCTD was confirmed by urine organic acid and OTC gene analysis.Patients with OTCD received guidance on diet and lifestyle management, and were treated with citrulline and arginine.Long-term follow-up was performed.Their growth and intellectual development were evaluated. Results:A total of 7 patients with OCTD were diagnosed, with an incidence of 1.6/1 million.All patients were males.Two patients had neonatal-onset OCTD, and the other 5 had late-onset OCTD.Symptoms occurred several times in 6 patients, inducing hyperammonemia and hepatic impairment.One patient had no clinical manifestation.One patient died in the neonatal period.Blood citrulline levels were decreased in 7 patients to varying degrees.Uracil levels were increased in 4 patients, and 1 of them was complicated with elevated orotic acid levels.All patients had hemizygote variations in the OTC gene, including 6 missense variations(c.604C>T, c.386G>A, c.779T>C, c.1019C>T, c.594C>G, c.931G>A) and 1 intron variation(c.514-35C>G). Two variants(c.594C>G, c.514-35C>G) were never reported previously. Conclusions:The OTCD incidence by newborn screening is low with 1.6/1 million in Zhejiang province.All patients are males and present hypocitrullinemia.The clinical manifestations of OTCD are highly heterogeneous.The neonatal-onset form is severe and survivors always suffer serious sequelae.The late-onset form is mostly manifested with hyperammonemia and hepatic impairment.There may be association between phenotype and genotype.Two novel OTC variants are identified, which further expands the mutational spectrum.

Aryl hydrocarbon receptors regulate pyocyanin-induced inflammatory factor expression in macrophages via p38MAPK/p65NF-κB signaling pathway / 中国药理学通报

Aim To investigate the effect of the aryl hydrocarbon receptor (AhR) on the expression of inflammatory factors in macrophages RAW264. 7 induced by pyocyanin (PCN) and the regulatory mechanism of its signaling pathway. Methods RAW264. 7 cells were treated with different concentrations of PCN for 24 h, respectively, and the effect of PCN on cell activity was detected by CCK8 assay to determine the optimal PCN concentration for manufacturing infection models. The cells were divided into the control group (given 0. 1% dimethyl sulfoxide DMSO), PCN group, PCN + AhR inhibitor (CH223191) group, and PCN + AhR agonist (FICZ) group, and the expression of AhR was detected by immunofluorescence. The expression levels of inflammatory factors (IL-6, IL-1β, and TNF-α) were detected by ELISA. The protein expression of AhR, pp38 MAPK and p-p65NF-κB, was detected by Western blotting. Results PCN induced a significant quantitative effect on AhR expression in RAW264. 7 cells. CH223191 increased PCN-induced inflammatory factor secretion and enhanced the phosphorylation of p38MAPK and p65NF-κB compared with the control group. FICZ decreased PCN-induced inflammatory factor production and reduced the phosphorylation of p38MAPK and p65NF-κB phosphorylation capacity. Conclusions AhR can regulate PCN-induced inflammatory factor expression in RAW264. 7 cells, and the p38MAPK/p65NF-κB signaling pathway may be an essential pathway for the involvement of AhR in immune regulation.

Lactate dehydrogenase inhibitor alleviates LPS/D-Gal-induced acute liver injury in mice / 中国药理学通报

Aim To investigate the effect of lactate dehydrogenase inhibitor on LPS/D-Gal-induced acute liver injury in mice. Methods BALB/ C mice were divided into four groups:solvent control group, lactate dehydrogenase inhibitor NHI-2 group, lipopolysaccharide(LPS)/ D-galactosamine(D-Gal)group and LPS/D-Gal+NHI-2 group. To induce acute liver injury, mice were injected intraperitoneally with LPS(10 μg·kg-1)and D-Gal(700 mg·kg-1), NHI-2 was intraperitoneally injected 30 min before LPS/D-Gal exposure. Liver tissue and serum were harvested 1.5 or 6 h after LPS/D-Gal exposure, serum lactate, serum aspartate aminotransferase(ALT), serum alanine aminotransferase(AST), serum tumor necrosis factor alpha(TNF-α)liver malondialdehyde(MDA)and liver caspase-3/8/9 levels were determined. HE staining was used to evaluate the degree of liver injury. TUNEL staining was used to evaluate hepatocyte apoptosis. Survival curve was used to record survival situation of tested mice. Results Serum lactate level of model mice was significantly reduced after treatment with NHI-2. Compared with LPS/D-Gal group, level of serum TNF-α showed no significant difference, but serum ALT and AST level of LPS/D-Gal+NHI-2 group significantly decreased, injury of liver structure was remarkably attenuated, level of MDA and activity of caspase-3/8/9 in liver were significantly down-regulated, and the number of TUNEL-positive cells was significantly reduced. Treatment with NHI-2 also significantly improved the survival rate of LPS/D-Gal-insulted mice. Conclusion Lactate dehydrogenase inhibitor alleviates LPS/D-Gal-induced acute liver injury in mice.

Effects of Sijunzi decoction-containing serum on polyamine/HuR signaling pathway during IEC-6 cell proliferation / 中国药理学通报

Aim To investigate the effect of Sijunzi Decoction on mRNA and protein expression related to growth and cell cycle in polyamine/HuR signaling pathway during small intestinal epithelial cell (IEC-6) proliferation, and to explore its mechanism on intestinal mucosal injury repair. Methods Sijunzi Decoction-containing serum (SJZD) was prepared from SD rats, the expression of HuR protein in cytoplasm and nucleus was analyzed by immunofluorescence and Western blot, the mRNA level of activating transcription factor-2 (A T F - 2), JunD and cyclin dependent kinase 4 (CDK4) were determined by real-time fluorescent quantitative PCR (RT-PCR), Western blot was used to detect protein level of HuR, ATF-2, JunD and CDK4, and flow cytometry was applied to analyse cell cycle distribution. Results Compared with the control group, the mRNA and protein expression of ATF-2 and JunD decreased, while the expression of Cdk4 mRNA and protein increased in SZJD group, and the proportion of G

A cell model for high-throughput screening GLP-1 receptor agonists / 中国药理学通报

Aim To establish a high-throughput screening cell model for GLP-1 receptor agonists. Methods A pEGFP-GLP-1R-3 C recombinant plasmid was constructed and transfected into HEK293T cells. The cells were screened with G418 and flow cytometry. The established stable cell line was named HEK293TGLP-lR-3C-eGFP cell line. The expression level of GLP-1 R-3C-eGFP protein was confirmed by Western blotting and laser confocal microscopy. Then cyclic adenosine monophosphate (cAMP) response element reporter gene was transfected into the HEK293T-GLP-lR-3C-eGFP cells. The luminescence values were detected by One-Step Luciferase Reporter Gene Assay Kit after stimulation with different concentrations of GLP-1 peptide. The luminescence values reflected the cellular cAMP level, which was verified using the cAMP kit (E L I S A). Results HEK293T-GLP-lR-3C-eGFP cell line was successfully constructed. The relative light unit change trend after stimulation with different concentrations of GLP-1 was similar to that of the cellular cAMP level change trend. The value of Z' in this experiment was 0.52. Conclusions A recombinant HEK293T cell line is established, which can be used for high-throughput screening of GLP-1 receptor agonists.

Baicalin modulates let-7i-3p/PI3K/Akt/NF-KB signaling axis to reduce NLRP3 inflammasome activation in fibroblast like synoviocytes of rheumatoid arthritis / 中国药理学通报

Aim To study the effect of baicalin on the activation of NLRP3 inflammasomes in human fibroblast like synoviocytes of rheumatoid arthritis ( HFLS-RA) and its mechanism. Methods To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA, immunofluorescence was used to observe the expression of NLRP3 before and after baicalin treatment. Western blot was used to detect the protein expression of p-PI3K, p-Akt, NF-κB p65, NL-RP3, ASC and caspase-1 after baicalin treatment for 48 h, and ELISA was employed to detect the contents of IL-1 and IL-18 in the supernatents. In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome, double luciferin and Westen blot analysis were applied to verify the corresponding relationship between let-7i-3p and PIK3CA. RT-qPCR was utilized to determine the expression of let-7i-3p and PI3K before and after baicalin intervention. let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasomes. Results Baicalin (50, 100 mg · L