ObjectiveSerum metabolomics of acute lung injury（ALI） in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） to explore the similarities and differences in the mechanism of Qingqiao（harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color） and Laoqiao（harvested when the fruits of Forsythiae Fructus were ripe） in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week， 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide（LPS）. After successfully constructing the ALI model， these rats was randomly divided into model group， Qingqiao group and Laoqiao group， with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg^-1， while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin（HE） staining， wet-to-dry mass ratio（W/D） of lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. The levels of interleukin（IL）-6， IL-1β and tumor necrosis factor（TNF）-α in BALF were quantified using enzyme-linked immunosorbent assay（ELISA）. UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao， and serum metabolomics of rats in each group was analyzed， combined with multivariate statistical analysis with variable importance in the projection（VIP） value>1， P<0.05 from t-test， and fold change（FC）≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group， rats in the model group exhibited enlarged alveolar lumen， ruptured alveoli， interstitial hemorrhage， bronchial exudation of a large number of neutrophils and erythrocytes， and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues（P<0.01）. In contrast， compared with the model group， rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs， and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased（P<0.01）， the lung injury was significantly alleviated， but more obvious in the Qingqiao group. Compared with the blank group， the expression levels of IL-6， IL-1β and TNF-α in the BALF of the model group were significantly higher（P<0.01）. Additionally， compared with the model group， the expression levels of IL-6， IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower（P<0.01）. The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao， with 47 common components， 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats， 19 and 12 metabolites were called back by Qingqiao and Laoqiao， respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， phenylalanine metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， glycerophospholipid metabolism， α-linolenic acid metabolism， and arachidonic acid metabolism， and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， arachidonic acid metabolism， sphingolipid metabolism， phenylalanine metabolism， ascorbate and aldarate metabolism， and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI， and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism， but the metabolic pathways affected by them are different.

Outpatient humanistic care refered to providing a full process of caring medical services to outpatients. In order to standardize the human caring services for outpatients in medical institutions, promote the comprehensive service level of outpatient services, and improve the patient′s medical experience, Chinese Association for Life Care issued the group standard of Management Norms for Human caring of Outpatients in April 2023. This standard clarified the relevant terms and definitions of human caring for outpatients, specified the basic requirements for human caring, the humanistic quality and care responsibilities of outpatient staff, the outpatient care environment and facilities, the outpatient care process and measures, and quality management. It designed standardized and personalized full process care service norms, providing references for medical institutions at all levels to promote the development of human caring for outpatients.

Objective:To explore the optimum time of ambulation of atrial fibrillation patients after radiofrequency ablation, to provide basis for patients' early postoperative rehabilitation.Methods:By convenient sampling method, a total of 120 patients with atrial fibrillation after radiofrequency ablation were collected at Yanghu Branch and City Branch of Changzhou Second People's Hospital from January 2020 to May 2021. They were divided into the early group, middle group and late group according to the random number table method, each group were 40 cases. All patients received routine postoperative intervention, the time of ambulation were 4, 6 and 12 h after operation in the early group, middle group and late group, respectively. The complication rate within 24 h after operation was compared among the three groups, and the comfort level of the three groups at 24, 48 and 72 h after operation was evaluated with Comfort Status Scale (GCQ).Results:Finally, 111 patients were included, including 37 in the early group, 38 in the middle group and 36 in the late group. There was no significant difference in the incidence of bleeding or hematoma, urinary retention, lumbago within 24 h after operation among the three groups ( P>0.05). The incidence of postural hypotension within 24 h after operation in the early group was 2.7% (1/37), which was lower than 21.1% (7/38) and 25.0% (9/36) in the middle and late groups, with a statistically significant difference ( χ2=4.86, 7.67, both P<0.05). At 48 and 72 h after operation, the scores of physiological dimension, psychological dimension and the total score of GCQ in the early group were (20.68 ± 3.07), (22.54 ± 3.35), (81.68 ± 6.11) and (22.54 ± 3.73), (24.38 ± 2.49), (84.92 ± 6.37), higher than those in the middle group (19.16 ± 2.19), (21.32 ± 2.27), (78.24 ± 5.58), (20.93 ± 2.85), (22.32 ± 2.04), (81.66 ± 6.56), and those in the late group (18.44 ± 1.50) (21.31 ± 1.99), (78.06 ± 4.32), (20.89 ± 2.25), (21.58 ± 1.86), (80.28 ± 6.44), the differences were statistically significant ( t values were 2.19-4.15, all P<0.05). Conclusions:Ambulation at 4 h after operation does not increase peripheral vascular complications, but can reduce the incidence of postural hypotension and improve the comfort of patients with atrial fibrillation after radiofrequency ablation.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

We report a case of a newborn baby who suffered from hemolytic disease of fetus and newborn (HDFN) caused by anti-Di a. The baby presented with worsening jaundice started at three hours after birth and was transferred to Dongguan Maternal and Child Health Care Hospital. The newborn's hemoglobin (Hb) was 82 and 76 g/L at five and nine hours after birth, and the total bilirubin (TBIL) was 243.2 and 309.8 μmol/L, respectively. Blood samples of the newborn and the parents were collected for HDFN immunohematology test twelve hours after birth. They showed that the newborn and the father's blood type was A and RhDCCee, while the mother was A and RhDCcee. Direct antiglobulin test (DAT) indicateda strong positive for the newborn and negative for the parents. The reaction of the reagent to red blood cells for antibody screening with the patient's plasma, red cells eluate, and the mother's plasma were all negative, but were positive with the father's red blood cells. The newborn was recovered after treating with phototherapy, intravenous immunoglobulins and urgent blood exchange (the exchanged blood was the same ABO and RhD blood type and cross-matched). The newborn's plasma and red cells eluate were collected before blood exchange, and the mother's plasma were used to assess the red blood cells reaction, and IgG anti-Di a was identified in each sample. Di a blood typing was positive for the newborn and the father, and negative for the mother. Therefore, the newborn was diagnosed as HDFN caused by anti-Di a.

Objective To analyze MR imaging appearance of pancreatic neuroendocrine neoplasms (pNEN) and to investigate the practical value of MR imaging appearance in predicting pathological grade of pNEN. Methods All data of 35 patients with pathologically proven pNEN were retrospectively reviewed. MR examinations of the abdomen were performed on all these patients before operation and the data of clinical, pathological and MR imaging were intact. Both plain scan and contrast-enhanced MR scan were performed on each patient. Histopathological grade of pNEN was defined as: G1, G2, and G3 according to World Health Organization classification of tumours of the digestive system guidelines(2010). Image analysis included tumor location, number, size, shape, lesion margins, signal intensity, enhancement pattern, main pancreatic duct dilatation, extrapancreatic spread, and metastases of lymph node and liver. The comparison of quantitative index between G1 and G2 group was performed with t test. Categorical variables were tested using Fisher exact test. Results Thirty five lesions were found in 35 patients, with 14 lesions in G1, 19 lesions in G2, and 2 lesions in G3.Thirty three lesions appeared as a solid mass, and 2 lesions appeared as a cystic lesion. Significant gender-based difference was found between G1 group and G2 group (P<0.05). No significant age-based or endocrine function difference was found between the G1 group and G2 group(P>0.05). Of the 35 lesions, 27 lesions were round in shape, while other 8 lesions were irregular. There were 18 lesions with clear margin, and the margins in other 17 lesions were blurred. Main pancreatic duct dilatation was found in 3 cases(1 in G2, 2 in G3). Significant differences in tumor diameter, shape, margin, signal intensity on precontrast images, extrapancreatic spread and metastases were found between G1 group and G2 group(P<0.05). No significant difference was found in main pancreatic duct dilatation or signal intensity on all enhancement phases between G1 group and G2 group. The 2 lesions in G3 group appeared mild contrast enhancement with degrees lower than the pancreas in all enhancement phases. Conclusion MR imaging features such as tumor diameter, shape, margin, signal intensity on precontrast images, extrapancreatic spread and metastases may preoperatively predict the pathological graden of pNEN.

OBJECTIVETo explore the molecular etiology for a Chinese family affected with isolated methylmalonic acidemia (MMA).

METHODSPotential mutations of MUT, MMAA and MMAB genes in the proband were screened by PCR and Sanger sequencing. The pathogenicity of identified mutations was analyzed using Polyphen2, SIFT, HSF, DNAMAN 6.0 and Swiss-PdbViewer4.1.0 software.

RESULTSTwo novel mutations of the MUT gene, including c.581C>T (p.P194L) and c.1219A>T (p.N407Y), were discovered in the proband, which were inherited respectively from his mother and father. Bioinformatics analysis suggested that both mutations were damaging. The affected codons P194 and N407, both located in the (beta, alpha) 8 barrel domain and to which the substrate methylmalonyl-CoA is bound, are highly conserved across various species. Both mutations can disrupt the space conformation of its protein product, affecting the function of the MCM protein.

CONCLUSIONThe novel mutations of MUT gene probably underlie the isolated MMA in this family.

Adult ; Amino Acid Metabolism, Inborn Errors ; enzymology ; genetics ; Amino Acid Sequence ; Animals ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Female ; Humans ; Infant ; Male ; Methylmalonyl-CoA Mutase ; genetics ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Pedigree ; Point Mutation ; Sequence Alignment

OBJECTIVETo explore the molecular mechanism for a boy suspected with 3-methylcrotonyl-CoA carboxylase deficiency by neonatal screening.

METHODSPCR and Sanger sequencing were used to identify potential mutations of MCCC1 and MCCC2 genes. SIFT and Polyphen-2 software was used to predict the effect of variant on the protein function and conservation of the variant across various species. Human Splicing Finder and Swiss-PdbViewer4.1.0 were applied to analyze the possible mechanism of the variant.

RESULTSFor the proband, a compound heterozygous mutation was discovered in the MCCC1 gene, namely c.539G>T (p.G180V) and c.704_711del (p.A235Vfs*4), which were inherited from his father and mother, respectively. The two mutations have disrupted the protein conformation, which in turn may impact the function of MCC protein.

CONCLUSIONThe compound heterozygous mutations of the MCCC1 gene may contribute to the 3-methylcrotonyl-CoA carboxylase deficiency manifested by the patient.

Amino Acid Sequence ; Base Sequence ; Carbon-Carbon Ligases ; chemistry ; deficiency ; genetics ; DNA Mutational Analysis ; Heterozygote ; Humans ; Infant, Newborn ; Male ; Models, Molecular ; Mutation ; Neonatal Screening ; methods ; Protein Conformation ; Sequence Homology, Amino Acid ; Urea Cycle Disorders, Inborn ; diagnosis ; genetics

Objectives To explore the feasibility ofdiagnosis of Perimembranous Ventricular Septal Defect with Right Aortic Valve Prolapse by ultrasonic echocardiography. Methods 131 VSD patients aged 1 to 22 years, weight 8.0 to 54.0 kg, underwent transthoracic echocardiography (TTE) and left ventricular angiography to show the diameter of VSD and the degree of AVP. Results Among 131 patients, 87 cases were diagnosed as VSD,14 as VSD with slight AVP, 12 as, VSD with middle AVP, and 18 as VSD with severe AVP by ultrasonic echocardiography respectively. After the left ventricular angiography and aortic root angiography , it proved that positive rate of VSD was 44.8%, positive rate of VSD with slight AVP was 42.86%, positive rate of VSD with middle AVP was 58.3%,and positive rate of VSD with severe AVP was 83.3%. Conclusion The transthoracic echocardiography (TTE) contributes to diagnosis of severe degree of AVP,while TTE evaluates the slight degree of AVP incorrectly enough. Left ventricular angiography and aortic root angiography are needed to realize the di-agnosis of AVP.

Objective To clone and identify the heat shock factors(HSFs)of Schistosoma japonicum and analyze its molec?ular structure and alternative splicing pattern. Methods The New Zealand rabbits were infected with the cercariae of Schistoso?ma japonicum and were killed and dissected 42 days post?infection,and the adult worms of S. japonicum and the livers of the rabbits were harvested. Then,the total RNA was extracted by using Trizol reagent. The Sj?hsf open reading frame(ORF)and the alternative splicing fragments were amplified by RT?PCR from the female,male and egg samples,then cloned and verified by enzyme digestion and sequencing. DNAMAN 8.0,InterPro,Mega 6 combined with the Internet databases were utilized to clarify the gene structure,functional domains,alternative splicing pattern,and the homology and phylogenetic tree of HSFs. Re?sults Sj?hsf ORF and the alternative splicing fragments were amplified from the female,male and egg samples of S. japonicum by RT?PCR. After cloning,the positive recombinant plasmids pBSjHSFf?F,pBSjHSFf?M,pBSjHSFf?E containing Sj?hsf ORF, pBSjHSFs?F,pBSjHSFs?M,pBSjHSFs?E with Sj?hsf alternative splicing fragments were identified by enzyme digestion and se?quencing. Three alternative splicing Sj?hsf isoforms were observed through sequence analysis:Sj?hsf?isoform1(2 050 bp),Sj?hsf ?isoform2(2 086 bp)and Sj?hsf?isoform3(2 111 bp);the GenBank accession numbers were KU954546,KX119143 and KX119144,respectively. All the three isoforms located in the same Contig SJC_S000780 of S. japonicum genome and all ex?pressed at female,male and egg stages,but Sj?hsf?isoform1 with a high?level expression. Sj?HSF?isoform1(671 aa)and Sj?HSF?isoform2(683 aa)had DBD(DNA binding domain),HR?A/B and HR?C domains,while Sj?HSF?isoform3(282 aa)stopped in advance without HR?C domain. Phylogenetic tree analysis of HSFs illustrated that Sj?HSFs belonged to HSF1 family,with a close phylogenetic relationship to Sm?HSFs. Conclusions There are three alternative splicing isoforms of Sj?HSF existing in the female,male and egg stages of S. japonicum,but Sj?HSF?isoform1 expresses in a high?level. This study lays the foundation for further study on molecular mechanisms of Sj?HSFs in regulating the heat shock response system.