OBJECTIVE ToinvestigatethepossibleprotectiveeffectofTripterygiumwilfordiipolyg-lycoside (TWP ) on experi mental diabetic nephropathy (D N ) rats and its possible mechanis m. METHODS Thediabeticmodelwasinducedbyasingleintraperitonealinjectionofstreptozotocin (STZ)65 mg·kg -1 .Three weeks after modeling,TWP 4.5,9.0 and 1 8.0 mg·kg -1 was ig given to rats,once daily,for 8 consecutive weeks.During the experiment,the changes of body mass,hair, mental health of rats were observed.Two days before the end of the experi ment,the rats were placed into metabolic cages to collect 24 h urine in order to detect 24 h urinary albu min excretion rate (UAER). The rats were given TWP for 8 weeks and anesthetized with 1 0%chloral hydrate.The blood was collect-ed fro m the heart and centrifuged,seru m creatinine and urine creatinine were measured,and creatinine clearance (Clcr)was calculated.Blood urea nitrogen (BUN)and the serum catalase (CAT)activity were tested by optical method while the level of seru m superoxide oxygen anion(O2÷)was tested by col-orimetry.The level of malondialdehyde(MDA)was determined by thiobarbituric acid condensation,and glutathione peroxidase (GSH-Px)activity was tested by colorimetry.The right kidney was HE stained to observepathologicalchanges.RESULTS Comparedwithnormalcontrolgroup,theratsinmodel control group developed polydipsia,polyuria,polyphagia,body mass loss,unresponsiveness,brown hair,pale tail and apathy clammy.Besides,blood glucose,BUN and 24 h UAER were significantly higher (P<0.01 ),but Clcr was lower (P<0.01 ).The activity of serum CAT and GSH-Px in renal tissue was significantly lower(P<0.01 ),while the level of serum O2÷ and MDA in the renal tissue was significantly higher(P<0.01 ).Compared with model control group,TWP 9.0 and 18.0 mg·kg -1 could improve the general condition of rats.BUN and 24 h UAER were obviously reduced(P<0.01 ),Clcr and serum CAT were increased obviously(P<0.01 ),the level of MDA and O2÷ were reduced obviously(P<0.01 ),and GSH-Px level was increased(P<0.01 ).TWP 9.0 and 18.0 mg·kg -1 could significantly im-prove the renal histopathological changes of rats.TWP 4.5 mg·kg -1 had no significant effect on the aboveindicators.CONCLUSION TWPhasprotectiveeffectontherenalfunctionofexperimentalDN rats.The mechanis m may be related to inhibition of the oxidative stress and enhance ment of the body antioxidant capacity.

Objective To investigate the effect of long-term walking exercise on the health status of low-labor-intensity population under long-term walking exercise.Methods A total of 100 volunteer teachers from universities in Beijing were enrolled.After physical examination,they were randomly divided into control group and observation group.The observation group regularly carried out corresponding encouragingactivities and recorded the daily number of steps.The corresponding indexes were measured again after 450 days.Results 45.24％ participants in the observation group got more than 75％ participation rate.The lower the participation rate,the lower the average daily steps (P ＜ 0.05).The fasting blood glucose,systolic blood pressure,LDL and total cholesterol were lower than other groups in the group participation rate ＜25％ (P ＜0,05).The body mass index,systolic blood pressure,fasting blood glucose,total cholesterol,ratio diabetes and hypertension in low activities group (＜ 7 500 steps/day) were lower than those in other groups (P ＜ 0.05).Conclusions Walking exercise can achieve good long-term persistence with constant feedback.For those who are older and whose initial indicators are higher,participation rate and exercise volume are more likely to be better under the guidance of encouragement.Persisting long-term walking exercise can help reduce blood pressure and blood lipids.

Objective:To compare the efficacy and safety of minimally invasive puncture and drainage for hypertensive cerebral hemorrhage at different time windows.Methods:A total of 98 patients with spontaneous cerebral hemorrhage underwent minimally invasive puncture and drainage in our hospital from January 2016 to December 2019 were chosen. These patients were divided into 3 groups in accordance with operation time: an ultra-early-stage group (accepted surgery within3 h of onset), an early-stage group (accepted surgery within 3-24 h of onset), an acute-stage group (accepted surgery within 24-72 h of onset); the clinical data of these patients were retrospectively analyzed. The hematoma clearance, muscle strength improvement 14 d after surgery, consciousness improvement 14 d after surgery, National Institutes of Health Neurological Deficit Scale (NIHSS) scores 14 d after surgery, and re-hemorrhage were compared among the 3 groups.Results:In the ultra-early-stage group, there were 11 patients (84.6%), 2 patients (15.4%) and 0 patients (0%) with low, medium and high hematoma clearance rates. In the early-stage group, there were 20 patients (33.9%), 32 patients (54.2%) and 7 patients (11.9%) with low, medium and high hematoma clearance rates. In the acute-stage group, 8 patients (30.8%), 14 patients (53.8%) and 4 patients (15.4%) had low, medium and high hematoma clearance rates. The hematoma clearance rate in the early group and the acute group was higher than that in the ultra-early group. Fourteen d after surgery, the proportion of patients with muscle strength improvement in the early-stage group and acute-stage group was significantly higher than that in the ultra-early-stage group ( P<0.05); the proportion of patients with consciousness improvement in the early-stage group was significantly higher than that in the ultra-early-stage group and acute-stage group ( P<0.05); NIHSS scores of patients in the early-stage group were significantly lower than those in the ultra-early stage group and acute-stage group ( P<0.05). There were 4 patients with postoperative re-hemorrhage, including one from the ultra-early-stage group and 3 from the early group. Conclusion:In patients with cerebral hemorrhage, hematoma clearance is relatively good and postoperative recovery is good when minimally invasive puncture and drainage is performed within 3-24 h of onset.

Objective To investigate the feasibility of Region 4 Stork(R4S)project used for newborn screening by tandem mass spectrometry in China.Methods This retrospective study was performed among 362 822 neonates screened by tandem mass spectrometry from May 2015 to April 2016 in Zhejiang newborn screening center.Infants were grouped by screening result category: 83 true positive cases,360 554 true negative cases and 2 185 false positive cases.Raw data was uploaded into R4S website to perform postanalytical interpretive tools, then results were analyzed with interpretation rules.The comparisons of normal population percentiles were done at five selected percentiles between Zhejiang newborn screening center and R4S project with min-max normalization.Results Compared with cutoff system by using R4S project with interpretation rules,the positive predictive value increased from 3.7%to 8.3%,the specificity increased from 99.40%to 99.75%, and the false positive rate declined from 0.6% to 0.2%. The two cases of true positive hyperprolinemia were reported negative, and one case of β-ketothiolase deficiency was misdiagnosis.Totally 311 638 cases in true negative group were resolved by postanalytical interpretive tools,and the remaining 48 916 cases were excluded with interpretation rules.False positive cases were reduced to 897 cases.Results of percentiles comparison showed that levels of some markers were significantly different between zhejiang newborn screening center and R 4S project.Conclusions R4S project effectively improved the newborn screening performance, whereas leaded to a small number of misdiagnosis and missed diagnosis.Besides,many true negative cases should be excluded with interpretation rules.Optimization should be achieved based on local normal population.(Chin J Lab Med,2018,41:300-304)

Objective:To investigate the application feasibility of Region 4 Stork (R4S) system, an international collaborative newborn screening data platform, combined with cut-off value analysis in the neonatal screening for very long chain acyl-CoA dehydrogenase deficiency (VLCADD) by tandem mass spectrometry (MS/MS).Methods:The retrospective study was performed in 2, 040 072 neonates screened by MS/MS in Neonatal Screening Center of Zhejiang Province, China from October 2013 to July 2018. Nine hundred and ten cases were determined and identified as suspected positive VLCADD neonates by traditional cut-off method of tandem mass spectrometry. The original data of these 910 screened neonates were further analyzed by R4S system. Based on clinical diagnosis and ACADL gene test results, the screening efficiency between two methods was statistically compared.Results:The data of 910 suspected VLCADD-positive cases interpreted by cut-off method were further analyzed by R4S system, and the positive interpretation was reduced to 238 cases (including 9 confirmed positive cases). A total of 16 different mutations were found in ACADL gene sequencing among the confirmed children. The screening false positive rate (FPR) declined from 0.44‰ (901/2 040 072) to 0.11‰ (229/2 040 072), the rate of positive predictive value (PPV) increased from 0.99% (9/910) to 3.78% (9/238), and the specificity increased from 99.96% (2 039 162/2 040 063) to 99.99% (2 039 834/2 040 063). There was a statistically significant difference between cut-off method alone and cut-off method combined R4S system analysis (χ2=393.5, P<0.05). Conclusions:The R4S system combined with cut-off method applied in VLCADD neonatal screening by MS/MS can effectively improve screening performance, reduce false positive rate, and has certain value in clinical application.

Objective To investigate the risk factors for myocardial injury after Nano-Knife surgery in patients with pancreatic cancer, and to establish a nomogram model for risk prediction. Methods A retrospective analysis was performed for the clinical data of 92 patients with pancreatic cancer who underwent Nano-Knife surgery in The Fifth Affiliated Hospital of Zhengzhou University from September 2020 to November 2021, with serum cardiac troponin I > 0.03 ng/mL within 3 days after surgery as the diagnostic criteria for myocardial injury, the patients were divided into myocardial injury group with 51 patients and non-myocardial injury group with 41 patients. Related baseline data were collected for all patients, including age, sex, body mass index, American Society of Anesthesiologists classification, smoking history, alcohol abuse history, and preoperative comorbidities. The Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Univariate and multivariate logistic regression analyses were used to screen out the variables with statistical significance, and the factors screened out were used to establish a nomogram for predicting the risk of myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the discriminatory ability and clinical utility of the model. Results Compared with the non-myocardial injury group, the myocardial injury group had a significantly longer ablation time ( χ 2 =7.410, P =0.006), a significantly greater number of probes ( χ 2 =6.130, P =0.047), and a significantly higher proportion of patients with preoperative hypertension ( χ 2 =12.124, P < 0.001) or chronic kidney disease ( χ 2 =12.829, P < 0.001). The univariate logistic regression analysis showed that tumor diameter, ablation time, surgical procedure, number of probes, history of hypertension, and history of chronic kidney disease were associated with the development of myocardial injury (all P < 0.05), and the multivariate logistic regression analysis showed that tumor diameter (odds ratio [ OR ]= 3.94, 95% confidence interval [ CI ]: 1.09-14.18, P =0.036), ablation time ( OR =4.15, 95% CI : 1.30-13.27, P =0.016), surgical procedure ( OR =6.92, 95% CI : 1.92-25.07, P =0.003), and history of hypertension ( OR =4.07, 95%CI: 1.12-14.77, P =0.034) were independent risk factors for myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. An AUC of 0.859 showed that the nomogram had good discriminatory ability and clinical utility. Conclusion There is a relatively high incidence rate of myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. Preoperative hypertension, tumor diameter > 4 cm, and ablation time > 1 hour are independent risk factors for myocardial injury, and the surgical procedure of Nano-Knife surgery and bypass anastomosis can increase the risk of myocardial injury. The nomogram has a good effect in predicting the risk of myocardial injury.

OBJECTIVE To explore the effects and mechanism of Bielong ruangan decoction on liver cancer model rats. METHODS Thirty-two male SD rats were randomly divided into control group， model group， and Bielong ruangan decoction low- dose and high-dose groups [6.84， 27.36 g/（kg·d）， by raw material]， with 8 rats in each group. Except for the control group， other groups were intraperitoneally injected with diethylnitrosamine （DEN） 50 mg/kg （once a week， for 16 consecutive weeks） to induce liver cancer model. At the 8th week of DEN injection， Bielong ruangan decoction low-dose and high-dose groups were orally administered with the corresponding medication， twice a day， until the 16th week. The general condition of rats in each group was observed during the experimental period. After the final administration， the body weight and liver mass were weighed， and the liver indexes were calculated； serum contents of alanine transaminase （ALT） and aspartate transaminase （AST） were determined； the appearance， pathological morphology and degree of fibrosis of liver were observed； Ishak scoring for liver fibrosis was performed； the mRNA and protein expressions of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， caspase-1， gasdermin D （GSDMD）， interleukin-18 （IL-18）， IL-1β in liver tissue were detected. RESULTS Compared with the model group， the general condition of rats （except for the low-dose group）， liver texture， surface nodules and tumors， inflammatory cell infiltration and abnormal cell amount were all improved in Bielong ruangan decoction low-dose and high-dose groups. Liver index （except for low-dose group）， Ishak score （except for low-dose group）， the serum contents of ALT and AST， as well as the mRNA and protein expressions of NLRP3， caspase-1， GSDMD， IL-18 and IL-1β in liver tissue were reduced significantly （P＜0.05）， with some of above indicators in high-dose group being significantly lower than those in low-dose group （P＜0.05）. CONCLUSIONS Bielong ruangan decoction can inhibit the progression of liver cancer in rats and reduce liver damage. Its mechanism of action may be related to the inhibition of the NLRP3/caspase-1/GSDMD signaling pathway and the improvement of inflammatory response.

OBJECTIVE: To explore effects of different delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots (DBS), so as to provide evidence for improving accurate and reliable detection by tandem mass spectrometry. METHODS: A total of 1 254 616 newborn DBS samples in Newborn Screening Center of Zhejiang Province were delivered and stored at room temperature (group A, RESULTS: The concentrations of amino acids and carnitines in the three groups were skewed, and the differences in amino acid and carnitine concentrations among groups were statistically significant (all CONCLUSIONS Cold-chain logistics system and storage in low temperature and low humidity can effectively reduce degradation of some amino acids and carnitines in DBS, improve the accuracy and reliability of detection, and thus ensures the quality of screening for neonatal metabolic diseases.
Amino Acids/analysis* ; Carnitine/analysis* ; Dried Blood Spot Testing/standards* ; Humans ; Humidity ; Infant, Newborn ; Neonatal Screening ; Reproducibility of Results ; Specimen Handling/standards* ; Tandem Mass Spectrometry ; Temperature ; Time Factors

An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties. The laboratory results indicated hyperlactatemia, elevated markers of myocardial injury and inflammation, and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry. Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy. Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup (p.T498Nfs*13) and c.1376T>C (p.F459S) in the ATAD3A gene, inherited from their father and mother, respectively. The diagnosis of Harel-Yoon syndrome was confirmed. The proband and her sister were born with clinical manifestations of metabolic acidosis, hyperlactatemia, feeding difficulties, elevated markers of myocardial injury as well as cardiac insufficiency, and both died in early infancy.
Humans ; Infant, Newborn ; Female ; Aged ; Mutation ; Hyperlactatemia ; ATPases Associated with Diverse Cellular Activities/chemistry* ; Membrane Proteins/genetics* ; Mitochondrial Proteins/genetics*

OBJECTIVE: To investigate the incidence,clinical,biochemical and genetic characteristics of isovaleric acidemia (IVA) in Zhejiang province. METHODS: Between January 2009 and December 2019, a total of 3 510 004 newborns were screened for IVA using tandem mass spectrometry. Patients of IVA were confirmed by urine organic acid and RESULTS: A total of 15 patients with IVA were diagnosed, with an incidence of 1/234 000. Three patients had acute neonatal IVA, and the rest were asymptomatic. The isovalerylcarnitine (C5) levels were increased in all patients. Twelve children underwent urinary organic acid analysis, of which 11 cases had elevated isovalerylglycine levels, 4 cases with 3-hydroxyisovalerate increased simultaneously. Eleven IVA patients underwent genetic testing, 9 patients were compound heterozygous variants in CONCLUSIONS The clinical manifestations of IVA are non-specific, and the gene spectrum is scattered. Newborn patients screened by tandem mass spectrometry can receive early diagnosis and treatment, so as to correct metabolic defects and pathophysiological changes.
Amino Acid Metabolism, Inborn Errors/epidemiology* ; Child ; China/epidemiology* ; Humans ; Infant, Newborn ; Isovaleryl-CoA Dehydrogenase/genetics* ; Mutation ; Neonatal Screening ; Tandem Mass Spectrometry