Identification, expression and protein interaction analysis of Aux/IAA and ARF gene family in Senna tora L / 药学学报

The early response of plant auxin gene family Aux/IAA (auxin/indole-3-acetic acid) and its interaction with auxin response factor (ARF) are important pattern to regulate plant growth and development. This work identified 28 StoIAA and 24 StoARF members based on the whole genome data of the medicinal plant Senna tora L., which were classified into 10 and 8 subfamilies, respectively. Phylogenetic tree and collinearity analysis showed that S. tora has close evolutionary relationship with the IAA and ARF homologous genes of Glycine max, Medicago truncatula, and the segment duplication events dominate the expansion of StoIAA and StoARF. Gene structure analysis showed that the vast majority of StoIAA and StoARF contain characteristic conserved domain. Transcriptome data showed that StoIAAs and StoARFs were expressed in leaves, roots and seeds, some members had tissue specific expression. The StoIAA and StoARF promoter region most contain functional elements related to stress response, growth and development, hormone induction and secondary metabolism. In addition, gene expression analysis showed that many StoIAAs and StoARFs can quickly respond to drought and salt stress and exhibited same expression patterns under both stress condition. The yeast two-hybrid experiment confirmed that StoARF8 and StoARF10 exhibit varying degrees of interaction with multiple StoIAA proteins, respectively. The above results provide a basis for further biological functional analysis of the Aux/IAA and ARF gene family of S. tora.

Characterization of the complete chloroplast genome of Polygonatum franchetii Hua, a Chinese endemic medicinal species, and phylogenetic relationships of Polygonatum / 药学学报

italic>Polygonatum franchetii Hua is a medicinal plant endemic to China from Polygonatum Mill. The chloroplast genomes of two P. franchetii individuals sampled from two different habitats were sequenced by using the DNBSEQ-T7 high-throughput sequencing platform. After assembly and annotation, the two complete chloroplast genomes were characterized, and then comparative and phylogenetic analyses were performed with other published chloroplast genome sequences from Polygonatum. The whole chloroplast genomes of the two P. franchetii individuals were 155 942 and 155 962 bp in length, with a large single copy region (LSC, 84 670 and 84 722 bp), a small single copy region (SSC, 18 564 and 18 566 bp) and a pair of reverse repeats (IRa/IRb, 26 354 and 26 337 bp), respectively. Both of them contained 113 genes, including 79 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. Comparative analyses showed that the genome length, the guanine and cytosine (GC) content, genes content and order were highly conserved between the two P. franchetii individuals and among different Polygonatum species. The detected repeat sequences, including dispersed repeats, tandem repeats and simple sequence repeats (SSRs), were also relatively similar in types and positions, though showing a slightly difference in number. No significant expansion or contraction of the inverted repeat regions was found. Sequences variation between the two P. franchetii individuals was lower than that among different Polygonatum species. Besides, coding sequences (CDS) showed less divergence than noncoding sequences, and sequence divergence of IRs regions was lower than that of the LSC and SSC regions, both intraspecifically and interspecifically. Eight sequences with high nucleotide diversity among different species were screened, all of which were found located in the LSC and SSC regions. Phylogenetic inference showed that all Polygonatum species clustered into a monophyletic clade with a 100% bootstrap value, within which, species in section Verticillata formed a distinct group, section Sibirica and section Polygonatum were sister groups. The two P. franchetii individuals grouped together and showed the closest phylogenetic affinity to P. stenophyllum Maxim., belonging to the section Verticillata. The chloroplast genome of P. franchetii and its phylogenetic position in Polygonatum were comprehensively investigated and clearly elucidated in this study, the results may lay a foundation for the resource development and utilization of P. franchetii, as well as further molecular identification and phylogenetic studies of medicinal Polygonatum species.

Phylogenetic analysis of chloroplast genome of Tussilago farfara L / 药学学报

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.

Diurnal differences in acute gout attacks: A clinical study of male gout patients / 北京大学学报(医学版)

OBJECTIVE@#To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment.@*METHODS@#Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators.@*RESULTS@#A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 ∶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks.@*CONCLUSION@#No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.

One-stage revision using intra-articular vancomycin infusion effectively treats chronic prosthetic joint infection caused by Enterococcal / 中华外科杂志

Objective: To investigate the clinical effects of one-stage revision combined with intra-articular infusion of vancomycin in the treatment of chronic prosthetic joint infection (PJI) caused by Enterococcal. Methods: From May 2013 to June 2020,the clinical data of 9 patients (2 males and 7 females) with chronic Enterococcal PJI treated with one-stage revision using intra-articular infusion of vancomycin at Department of Orthopaedics,First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed,including 8 hips and 1 knee.A total of 9 patients with age of (63.9±11.7)years (range:43 to 76 years) were included, and the body mass index was (23.6±4.3)kg/m2 (range:18 to 30 kg/m2).There were 6 cases with antibiotic history and 5 cases with sinus tract.The joint fluid,infected tissue around the prosthesis and ultrasonic shock fluid of the prosthesis were collected during operation for microbial culture identification and drug sensitivity test.After thorough debridement of the infected site and removal of the infected prosthesis,a new prosthesis was implanted,then the drainage tube in the operation area was placed.After surgery,vancomycin(1.0 g,q12 h) was combined with intra-articular vancomycin(0.5 g,qd) in monomicrobial PJI,and vancomycin(1.0 g,q12 h) was combined with intra-articular vancomycin (0.5 g,qd) and imipenem/meropenem (0.5 g,qd),and the interval between the two drugs was 12 hours in polymicrobial PJI.Hip and knee functions were evaluated by Harris Hip Score or Knee Society Score(KSS),respectively.The comparison of hip function scores before and after operation was performed by paired t-test. Results: All patients were followed up for (60±39)months(range:24 to 110 months).Two cases were infected with Enterococcus faecium and 7 cases were infected with Enterococcus faecalis.There were 7 cases of monomicrobial infection and 2 cases of polymicrobial infection.Erythromycin(5/9),tetracycline(4/9),ciprofloxacin and β-lactam antibiotics(3/9) were the top three antibiotics in Enterococci resistance rate.The sensitive antibiotics for Enterococcal were vancomycin,linezolid and tigecycline.The average duration of intravenous antibiotics was (14±1)days (range:13 to 17 days),and the average duration of antibiotics in articular cavity was (15±2)days(range:11 to 20 days).Mean duration of oral antibiotic use after discharge was (2±1)months(range:1 to 3 months).One case of polymicrobial PJI treatment failed,with a failure rate of 1/9.At last follow-up,the Harris score of patients with hip PJI increased from (43±6)points to (84±6)points(t=-11.899, P<0.01). KSS score of knee function was improved from 33 point pre-operatively to 85 point post-operatively;overall function score was improved from 35 point pre-operatively to 80 point post-operatively.During the treatment,no formation of sinus tract of the hip joint caused by a catheter,skin necrosis at the knee puncture site or leakage of joint fluid;no complications such as deep vein thrombosis and pulmonary embolism occurred. Conclusions: One-stage revision combined with intra-articular infusion of vancomycin can achieve acceptable infection control rate and joint function in patients with chronic Enterococcus PJI.However,the treatment of polymicrobial PJI still needs to be further verified.

Correlation analysis of asthma and prognosis in 148 children with low immune function / 公共卫生与预防医学

Objective To analyze the effect of immune function on the condition and prognosis of asthma in children with asthma. Methods A total of 148 children with asthma diagnosed in Qinghai women and children's Hospital from January 2018 to January 2021 were included in the analysis, the immune function of the children was determined, and the information of all children was followed up for 6 months after treatment; compared The condition and follow-up prognosis of children with immunocompromised and normal immune function were analyzed and discussed, and the correlation between the expression levels of immunoglobulins (IgG, IgA, IgM) and the condition and short-term recurrence prognosis (6 months) of children was analyzed and discussed, so as to guide Prevention and clinical work. Statistical analysis was done using SPSS19.0. Results The average age of 148 children with recurrent respiratory tract infection in the study was (8.94±3.65) years old, including 70 male children. The condition of the children was evaluated and classified into mild/severe cases: 148 children in this study included mild cases. There were 98 cases and 50 severe cases. There were more males and lower BMI levels in severe children (P<0.05) . The levels of IgG, IgA and IgM in children were all lower in severe children (P<0.05) . The follow-up found that the proportion of relapses in critically ill children was higher (P<0.05). Comparing the levels of IgG, IgA, and IgM in mild and severe children, the average levels of IgG, IgA, and IgM in severe children were lower than those in the mild group, and the difference was statistically significant (P<0.05); recurrence within 6 months of follow-up Prognostic evaluation showed that 19 of the 148 children had relapse, and the levels of IgG, IgA, and IgM in severe relapsed children were significantly lower than those without relapse (P<0.05). Analysis of the relevant factors potentially affecting the prognosis of recurrence showed that gender (female) (OR=1.726) , BMI level (weight loss) (OR=1.613) , IgG expression level factor (low expression) (OR=1.898) , IgA expression Level factor (low expression) (OR=3.509) , IgM expression level factor (low expression) (OR=3.217) and disease factor (severe) (OR=3.619) were potential risk factors, which would increase the risk of poor prognosis. Conclusion The asthma attack in children with immunocompromised immune function is relatively severe, and the short-term recurrence probability is higher, which deserves clinical attention and preventive intervention.

Satisfaction of Patients with Above-the-knee Amputation following Periprosthetic Joint Infection / 中山大学学报(医学科学版)

ObjectiveThe purpose of this study was to evaluate the functional outcomes and satisfaction in periprosthetic knee infection patients after above-the-knee amputation （AKA）. MethodsA review was performed in 13 patients who underwent AKA due to periprosthetic knee infection from October 2010 to August 2022， there were 7 females and 6 males with the median age of 69 （45~ 73） years. The mean number of surgical procedures between primary total knee arthroplasty and AKA was 2.9 times （range： 1 ~ 6）. Patients were segregated into non-elderly group （including patients <65 years old） and elderly group （involving patients ≥65 years old）. Functional outcomes were evaluated by SF-12 and Barthel activities daily living index （Barthel ADL index）. Patient satisfaction was accomplished through a questionnaire. ResultsFour patients died within 6 months after the amputation. Three patients received surgical procedures for recurrent infections after AKA. In the remaining 9 patients，the median time from AKA to the final follow-up was 4.2 （1.9~8.2） years， three patients received surgical procedures for recurrent infections after AKA. Patients in non-elderly group showed better functional outcomes than elderly patients after AKA （both P<0.05）. All patients in non-elderly group were fitted with a prosthesis. Whereas， elderly patients reported a better satisfaction after AKA than young patients. ConclusionYoung PJI patients seemed to have better function and ambulatory ability with high expectation and demand， which made them feel less satisfied about AKA. Meanwhile，despite poor function outcomes due to the less healthy physical condition， the alleviation of financial and psychological burdens resulting from reinfections and multiple surgeries and the less demand in function and daily activities made elderly patients have a good satisfaction after AKA.

Common diseases and drug use characteristics of Chinese herbal medicines and suggestions / 中国中药杂志

Based on the data of 56 kinds of diseases and drug use in 100 kinds of cultivated Chinese herbal medicines, this paper used frequency analysis method to count the types of diseases and their drug use characteristics, and systematically analyzed the status of drug registration and monitoring standards for disease prevention and control of Chinese herbal medicines. The results showed that 14 diseases such as root rot, powdery mildew, and drooping disease were common in the production of Chinese herbal medicines. Among the 99 pesticides reported, 67.68% were chemically synthesized, 23.23% were biological pesticides, and 9.09% were mineral pesticides. Among the reported pesticides, 92.93% of them were low toxic, with relative safety. However, 70% of the production drugs were not registered in Chinese herbal medicines, and the phenomenon of overdose was serious. The current pesticide residue monitoring standards does not match well with production drugs in China. Although the matching degree between Maximum Residue Limit of Pesticide in Food Safety National Standard(GB 2763-2021) and production drugs is more than 50%, there are few varieties of Chinese herbal medicines covered. The matching degree between Chinese Pharmacopoeia(2020 edition), Green Industry Standard of Medicinal Plants and Preparations(WM/T2-2004), and production drugs is only 1.28%. It is suggested to speed up the research and registration of Chinese herbal medicine production and further improve the pesticide residue limit standard combined with the actual production, so as to promote the high-quality development of Chinese herbal medicine industry.

Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder / 中国医学科学院学报

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

Effect of Ursolic Acid on Proliferation and Apoptosis of Colorectal Cancer Cells Based on Akt/FoxO Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects and molecular mechanism of ursolic acid on the proliferation and apoptosis of colorectal cancer cells. MethodThe proliferation inhibition rate of human colorectal cancer RKO cells treated with different concentrations of ursolic acid （0， 5， 10， 15， 20， 25， 30 μmol·L-1） was detected by cell counting kit-8 （CCK-8）， and the half maximal inhibitory concentration （IC50） at 24 h and 48 h was calculated. According to the IC50 of RKO cells treated with ursolic acid for 24 h， two concentrations were selected for subsequent experiments. The colony formation assay was used to detect the proliferation ability of the cells and flow cytometry was used to detect the apoptosis rate and cell cycle arrest after treatment of RKO cells with ursolic acid. After treatment of RKO cells with ursolic acid for 24 hours， the expression of B-cell lymphoma 2 （Bcl-2）-associated X protein （Bax） in RKO cells， Bcl-2 in Raji cells， PMA responsive gene in T lymphocyte （Noxa）， cyclin-dependent kinase inhibitor 1A （p21）， cyclin-dependent kinase inhibitor 1B （p27）， cyclin-dependent kinase 4 （CDK4）， protein kinase B （Akt）， phosphorylated Akt （p-Akt）， forkhead transcription factor O3a （FoxO3a）， and phosphorylated FoxO3a （p-FoxO3a） was determined by Western blot. ResultCompared with the blank group， the ursolic acid groups could inhibit the viability of RKO cells （P<0.05， P<0.01）， and the colony formation rates of RKO cells in the ursolic acid groups were reduced （P<0.05， P<0.01） in a concentration-dependent manner. The cells in the ursolic acid group （20 μmol·L-1） experienced cell cycle arrest， which increased in the early stage of synthesis， ie， the G0/G1 phase （P<0.05） as compared with the results in the blank group. Compared with the blank group， the ursolic acid groups （15 and 20 μmol·L-1） showed increased protein expression of p21 and p27， decreased expression of CDK4 protein （P<0.05， P<0.01）， and increased apoptosis rate， and the ursolic acid group （20 μmol·L-1） showed increased protein expression of Bax and Noxa and decreased expression of Bcl-2 （P<0.05， P<0.01）. In terms of mechanism， compared with the blank group， the ursolic acid group （20 μmol·L-1） down-regulated the expression of p-Akt protein and up-regulated the expression of p-FoxO3a （P<0.05， P<0.01）， and there was no significant change in the total protein of Akt and FoxO3a. ConclusionUrsolic acid can effectively inhibit the proliferation of colorectal cancer RKO cells and promote cell apoptosis， which may be related to the Akt/FoxO pathway.

Genome-wide identification of GSK gene family in Senna tora L. and expression analyses / 药学学报

Glycogen synthase kinase 3/SHAGGY-like kinase (GSK3) proteins play important roles in regulating plant growth, development, and stress response. In order to reveal the characteristics of GSK family members in the medicinal plant Senna tora L., in this study, we conducted the identification and expression analyses of GSKs in S. tora based on its whole genome data, combined with bioinformatics and gene expression research methods. The results showed that a total of nine S. tora GSK genes were identified, all of which contained the GSK characteristic kinase domains. All members were distributed on six chromosomes, the encoding amino acid length ranged from 465 to 943 aa, the protein molecular weight was from 33.57 to 88.83 kDa, and the average isoelectric point was 8.2. The StoSKs were divided into four evolutionary branches, and the StoSKs in the same evolutionary branch shared the same exon/intron structure and conserved motifs. The expansion of the StoSKs gene family was mainly due to segment duplication events, and there were 17, 11, 8 and 7 pairs of collinear genes with Glycine max, Medicago truncatula, Arabidopsis thaliana and Oryza sativa, respectively. The promoter regions of StoSKs mostly contained responses elements related to stress stimulation, growth and development, and hormone induction. Transcriptome data analysis showed that StoSKs were expressed in different tissues, with the highest expression level in roots. Quantitative real-time PCR (qRT-PCR) analysis indicated that StoSKs in different evolutionary branches displayed a synergistic expression pattern response to light, and most of StoSKs could rapidly respond to NaCl stress with significantly up-regulated expression. All the results provide a basis for further analysis of the biological functions of the GSKs gene family in S. tora.

Identification and analysis of R1-MYB gene family in Rheum palmatum L. based on full-length transcriptome sequencing / 药学学报

As one kind of v-myb avian myeloblastosis viral oncogene homolog (MYB) transcription factors, R1-MYB (MYB-related) family plays an important role in plant growth and development, as well as environmental stress and hormone signal transduction. In this study, R1-MYB family genes in Rheum palmatum L. were systematically screened based on full-length transcriptome sequencing analysis. Firstly, the physicochemical, protein domain and molecular evolution characteristics of the coding proteins were analyzed. Furthermore, the tissue expression levels of R1-MYB genes were analyzed by RNA-seq. We also investigated the expression pattern of RpMYB24 in response to various hormones and abiotic stresses. The results showed that a total of 49 R1-MYB genes were identified, which mainly encoded thermally stable hydrophilic proteins. Most of the deduced proteins were predicted to locate in nucleus. Each protein had a large proportion of random curl and α helix, and also had the W-type conserved amino acids which were the signature of MYB. R1-MYB family members were distributed in five subgroups, including circadian clock associated 1 (CCA1)-like, I-box (GATAAG)-like, CAPRICE (CPC)-like, telomere repeat binding factor (TRF)-like and TATA binding protein (TBP)-like, and the number of CCA1-like was the majority. RNA-seq revealed that 49 R1-MYB genes were differentially expressed in roots, rhizomes and leaves of R. palmatum, and the expression levels of 15 and 23 genes in roots and rhizomes were higher than those in leaves, respectively. RpMYB24 transcript was induced by abscisic acid (ABA), salicylic acid (SA), and methyl jasmonate (MeJA) treatment, and could also significantly respond to injury, low temperature and high temperature stresses except drought stress. This study systematically identified the R1-MYB family genes and their molecular characteristics, better for further gene functional validation, and then provide a scientific basis for the transcriptional regulation mechanism research into rhubarb quality formation.

Efficacy and safety of balloon dilation technique during ureteroscopic lithotripsy with "difficult ureter" / 中华泌尿外科杂志

Objective:To summarize the preliminary clinical experience of utilizing ureteral balloon dilation catheter in the treatment of "difficult ureter" during ureteroscopic lithotripsy, and to discuss the efficacy and safety of the technique.Methods:Clinical data of 28 patients (30 sides) with upper urinary tract calculi admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2021 to July 2022 were retrospectively analyzed. There were 23 males (82.1%) and 5 females (17.9%), with age of (51.5±13.6) years. Among the 30 sides, 20 (66.7%) on the left and 10(33.3%) were on the right. Calculi were either located in the renal pelvis or calyxes in 7 sides (23.3%), upper ureter in 17 sides (56.7%), and lower ureter in 6 sides (20.0%). The maximum diameter of the stones was (9.4±4.2)mm, and 23 sides (76.7%) were combined with hydronephrosis before surgery. When "difficult ureter" was encountered during the procedure, that is, it was difficult to insert ureteroscope or ureteral access sheath (UAS) due to small ureteral lumen, balloon catheter was used for dilation in the first stage, in which the balloon diameter was 4 mm on 22 sides and 5mm on 8 sides. The instrument was retrogradely inserted through the working channel of F8 semi-rigid ureteroscope, and the small site of the ureteral lumen was dilated under direct endoscopic view. After a single dilation, the balloon catheter was withdrawn, and the effect of dilation was evaluated by semi-rigid ureteroscopy to determine whether to proceed with the following procedures. The intraoperative data were recorded, including surgical method, stage of "difficult ureter" occurred, site of the small part of the ureter, related data of utilizing ureteral dilatation balloon catheter, grade of ureteral injury after dilatation (according to the 0-4 grading classification of endoscopic ureteral injuries), total operation time, balloon catheter-related adverse events, stone-free rate, and time of removing ureteral stents.Results:Among the 30 sides, 29 (96.7%) had difficulty in the stage of ureteroscope insertion, and 1(3.3%) had difficulty in the stage of UAS insertion. A total of 37 small sites of ureter were involved, including 18 in the intramural segment, 10 in the lower part, 2 in the middle part, and 7 in the upper part. Each site was dilated once with a median time of 3 (0.5, 5.0) minutes and a median maximum balloon pressure of 1 215.9(1 215.9, 1 443.9)kPa[12.0(12.0, 14.3)atm]. There were 28 sites of grade Ⅰ injury, 8 sites of grade Ⅱinjury, and 1 site of grade Ⅲinjury. The total duration of unilateral procedure was (73.4±30.3) min. Ureteroscope or UAS insertion was successful in 28 sides(93.3%) after balloon dilation, and failed in 2 sides(6.7%), both of which were in the stage of inserting ureteroscope and ureteral stent was indwelled for the second-stage procedures. On the first day after surgery, the hemoglobin level was (134.1±12.9)g/L, which was significantly different from the preoperative parameters ( P<0.01), and serum creatinine level was (86.7±23.2)μmol/L, which showed no significant difference from the preoperative one ( P=0.263). The primary stone-free rate was 92.9% (26/28), and the total postoperative complication rate was 13.3% (4/30), including 3 of grade Ⅰ (lateral lower abdominal pain requiring additional analgesic drugs) and 1 of grade Ⅱ (postoperative hematuria requiring intravenous hemostatic drugs). Follow-up was conducted for 3 months. All of the 28 successful sides had their ureteral stents removed before the last follow-up, and the time of removal was (36.9±11.5) days. No hydronephrosis was found in the ipsilateral kidney by ultrasound 3 months after operation. Conclusions:Balloon dilation technique showed good efficacy and safety in the treatment of "difficult ureter" during ureteroscopic lithotripsy.

Study on characteristics of microvascular perfusion with superb micro-vascular imaging after tibia transverse bone transport for diabetic foot / 中华骨科杂志

Objective:To explore the clinical value of super micro vascular imaging (SMI) in evaluating the microvascular perfusion of diabetes foot treated by tibial transverse bone transport.Methods:A retrospective study of 18 diabetic foot patients who underwent tibial transverse bone transport in the Second Hospital of Shanxi Medical University from May 2019 to December 2021 were analysed, including 12 males and 6 females, with an average age of 64.89±14.34 years (range, 30-90 years). All patients had varying degrees of foot ulcer. Before and after the operation, the blood vessels of the patient's lower leg and foot were examined. The display rate of low-velocity blood flow was compared between color Doppler flow imaging (CDFI) and SMI; the blood flow and vascular index at the beginning of the first dorsal metatarsal artery before and after operation under SMI were compared; the number and length of new blood vessels were also compared before and after operation.Results:All patients were followed up for at least 2 months. CDFI blood flow display rate was 73.6% (106/144), and SMI blood flow display rate was 80.6% (116/144), the difference was statistically significant (χ 2=4.68, P=0.031). Under SMI, the blood flow at the beginning of the first dorsal metatarsal artery on the affected side was measured before operation 3.38 (1.33, 7.56) ml/min, 1 week after operation 4.19(2.84, 11.48) ml/min and 1 month after operation 3.72 (2.52, 11.40) ml/min, with statistically significant difference (χ 2=9.46, P=0.009). There were statistically significant differences in blood flow at 1 week and 1 month after operation compared with that before operation ( P=0.033, P=0.003). The vascular index at the beginning of the first dorsal metatarsal artery on the affected side was 3.84±3.60, 6.51±4.92 and 6.82±5.36 before operation, 1 week and 1 month after operation, respectively, and the differences were statistically significant( F=4.35, P=0.031). The vascular index in the first week after operation was significantly higher than that before operation ( P=0.026). Up to the last follow-up, the number of new collaterals in 18 patients was 4.5 (2, 8), which was significantly different from 1 (0, 2) before operation ( Z=-3.57, P=0.001). In total, the length of 18 new blood vessels in 9 patients was longer than that before operation, and the establishment of grade 2 and grade 3 branches were observed in 5 patients. The superficial subcutaneous vessels were showed more clarity than that before surgery, and there was collateral circulation on the opposite side. Conclusion:SMI objectively reflects the changes of hemodynamics and microcirculation of patients after tibial transverse bone transport, and helps clinical preliminary predict the prognosis of patients and adjust individual treatment plan according to blood perfusion in time.

Baseline NIHSS score and D-dimer in early prediction of large vessel occlusion in patients with acute ischemic stroke / 中华急诊医学杂志

Objective:Early identification of ischemic stroke patients with large vessel occlusion can improve referral efficiency and shorten reperfusion time. The purpose of this study was to analyze the characteristics of patients with large vessel occlusion and identify factors that could predict large vessel occlusion.Methods:The clinical data of 432 patients with ischemic stroke treated through emergency green channel were retrospectively analyzed, and the differences between the large vessel occlusion group (LVO group) and the non-large vessel occlusion group (non-LVO group) were compared, and two independent risk factors of the LVO group were screened out by logistics regression analysis: baseline NIHSS score and D-dimer value. The predicted cutoff values of NIHSS score and D-dimer were further determined by the receiver operating characteristic (ROC) curve.Results:A total of 432 patients with ischemic stroke had complete imaging data, with a mean age of 68.5±12.4 years, including 275 (63.7%) males, and 245 (56.7%) in the LVO group and 187 (43.3%) in the non-LVO group. Age, hemorrhagic transformation, thrombolytic therapy, endovascular treatment, atrial fibrillation, baseline NIHSS score [14.0 (6.0-20.0) vs. 3.0 (1.0-6.0), P<0.05], and D-dimer value at admission [0.9(0.4-2.3) mg/L vs. 0.3 (0.2-0.5)mg/L, P<0.05] were statistically significant different between the two groups. Multivariate Logistic regression analysis showed that higher baseline NIHSS score( OR=1.22,95% CI: 1.17-1.27)and higher D-dimer value( OR=3.10,95% CI: 2.14-4.47)were independent risk factors for large vessel occlusion. Baseline NIHSS score combined with D-dimer value was a good predictor of large vessel occlusion(AUC 0.85 [0.81-0.89]). ROC curve suggested that NIHSS score >6.5 and D-dimer >0.57 mg/L were the cutoff values for predicting large vessel occlusion. Conclusions:Higher baseline NIHSS score and D-dimer value are valuable for early prediction of large vessel occlusion, patients with NIHSS score >6.5 points and D-dimer >0.57 mg/L should be promptly transported to an advanced stroke center for treatment.

Role of Prognostic Marker PRR11 in Immune Infiltration for Facilitating Lung Adenocarcinoma Progression / 生物医学与环境科学（英文）

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.

Targeting fibroblast activation protein inhibits endothelial-mesenchymal transition by affecting cancer-associated fibroblasts derived exosomes / 中国药理学通报

Aim To investigate whether targeted inhibition of fibroblast activation protein (FAP) can inhibit the endothelial-to-mesenchymal transition (EndMT) of vascular endothelial cells by affecting exosomes (Exo) of cancer-associated fibroblasts (CAFs) and explore the underlying mechanisms. Methods Primary CAFs and peri-tumor fibroblasts (PTFs) were obtained from lung cancer and peri-cancer tissues, and CAFs-exo and PTFs-exo were collected from culture medium, respectively. Exosomes from CAFs treated with specific FAP inhibitor (3.3 nmol • L-

Carvedilol attenuates atherogenesis by regulating hepatic ACAD10 and mTOR in ApoE" " mice / 中国药理学通报

Aim To explore the effects of carvedilol on atherogenesis in mice. Methods Eight-week-old ApoE mice were placed on an atherogenic chow and randomly divided into control and carvedilol group. The mice in both groups were intraperitoneally administered with vehicle or carvedilol 12. 5 mg • kg once daily, respectively. After 10 weeks, histopathological alterations of brachiocephalic trunk, liver, pancreas and adipose tissues were assessed by hematoxylin and eosin and oil red 0 staining, the level of blood glucose, blood lipids, aspartate aminotransferase (AST) , alanine aminotransferase ( ALT) , and liver fatty acid P-oxidase were determined, and glucose tolerance/insulin tolerance tests were performed as well. In addition , hepatic mRNA and protein expression of ACAD10 and mTOR were detected by real-time PCR and Western blot, respectively. Results Compared with the control group, the area of atherosclerotic plaque ( P < 0. 01 ) and intima-to-media ratio ( P < 0. 05) in the carvedilol group all significantly de- creased , aortic damages were obviously improved, glucose and insulin tolerance were remarkably enhanced; moreover, HDL-C concentration in serum increased (P <0. 05) . Notably, HE and oil red 0 staining revealed that carvedilol almost completely reversed hepatic steatosis, increased liver fatty acid beta oxidase levels (P < 0. 01 ) , along with the reduction in ALT (P < 0. 01 ) and AST (P <0. 01) levels, even improvement of pancreatic and adipose impairments in ApoE mice. In carvedilol group, the mRNA (P <0. 01) and protein expression levels (P <0. 05) of ACAD10 were significantly up-regulated, while mTOR was significantly down-regulated compared with that in the control group (P <0. 01). Conclusions Our results indicate that carvedilol regulates mTOR and ACAD10 in liver, which may contribute to the alleviation of fatty liver, and even atherogenesis.

Alteration and significance of serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma: a retrospective study based on LEGEND-2 / 中华血液学杂志

Objective: To explore the dynamic changes in serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma (R/R MM) based on LEGEND-2. Methods: The data of patients with R/R MM who underwent BCMA-CAR-T therapy at our hospital between March 30, 2016, and February 6, 2018, were retrospectively collected. Serum lipid levels, controlled nutritional status (CONUT) score, and other clinical indicators at different time points before and after CAR-T-cell infusion were compared and analyzed. The best cut-off value was determined by using the receiver operator characteristic (ROC) curve. The patients were divided into high-CONUT score (>6.5 points, malnutrition group) and low-CONUT score groups (≤6.5 points, good nutrition group), comparing the progression-free survival (PFS) and total survival (OS) of the two groups using Kaplan-Meier survival analysis. Results: Before the infusion of CAR-T-cells, excluding triglycerides (TG), patients' serum lipid levels were lower than normal on average. At 8-14 d after CAR-T-cell infusion, serum albumin (ALB), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein A1 (Apo A1) levels dropped to the minimum, whereas CONUT scores reached the maximum. In addition to TG, apolipoprotein B (Apo B) levels increased compared with baseline. After CAR-T-cell therapy, the patients' serum lipid levels significantly increased with well-improved nutritional status. Spearman's related analysis showed that TC, HDL, and ApoA1 levels after CAR-T-cell injection were significantly negatively correlated with the grade of cytokine-release syndrome (CRS) (r=-0.548, P=0.003; r=-0.444, P=0.020; r=-0.589, P=0.001). Furthermore, survival analysis indicated that the CONUT score was unrelated to PFS, and the median OS of patients with R/R MM in the high-CONUT score group was shorter than that in the low-CONUT score group (P=0.046) . Conclusions: During CAR-T-cell therapy, hypolipidemia and poor nutritional status were aggravated, which is possibly related to CRS. The patients' serum lipid levels and nutritional status were significantly improved after CAR-T-cell treatment. The CONUT score affected the median OS in patients treated with CAR-T-cells. Therefore, specific screening and intervention for nutritional status in patients receiving CAR-T-cell therapy are required.

Construction of a Mouse Model for Myeloproliferative Neoplasms and an Evaluation System / 中国实验血液学杂志

OBJECTIVE@#To construct a myeloproliferative neoplasms (MPN) transplanted mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation, and establish a systematic evaluation system to verify the success of model construction.@*METHODS@#The bone marrow c-kit+ cells of the mice were obtained by the following steps: The mice were killed by cervical dislocation, the femur, tibia and ilium were separated, and the bone marrow cells were collected. The c-kit+ cells were sorted after incubation with CD117 magnetic beads. The method of constructing mouse primary mutant cells is as follows: A gene mutation vector with a GFP tag was constructed by the retroviral system, and the retroviral vector was packaged into the Platinum-E cells to obtain the virus supernatant, and then used it to infect the c-kit+ cells of mice. The MPN mouse model was constructed as follows: the mouse primary c-kit+ cells containing the mutant genes were collected after infection, and then transplanted them via the tail vein into the female recipient mice of the same species which were irradiated with a lethal dose of gamma rays (8.0 Gy). The MPN mouse model was evaluated as follows: After transplantation, the peripheral blood of the mice was regularly collected from the tail vein to perform the complete blood count test, and the size of spleen and the degree of bone marrow fibrosis were estimated.@*RESULTS@#The mouse c-kit+ cells with the mutant genes were successfully obtained from the bone marrow. MPN mouse model was successfully constructed: The peripheral blood cells of the MPN-transplanted mice carried exogenous implanted GFP-positive cells, and the white blood cells (WBC), platelet (PLT) and hematocrit (HCT) were all increased; the body weight loss, and the water and food intake were reduced in the transplanted mice; further pathological analysis showed that the transplanted mice displayed splenomegaly and bone marrow fibrosis. These results suggested that the MPN mouse model was successfully constructed. According to the common and different characteristics of the three MPN mouse model, a preliminary evaluation system for judging the success of MPN mouse model construction was summarized, which mainly included the following indicators, for example, the proportion of GFP-positive cells in the peripheral blood of mice; WBC, PLT and HCT; the degree of spleen enlargement and the bone marrow fibrosis.@*CONCLUSION@#The MPN mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation is successfully established by retroviral system, which can provide an important experimental animal model for the research of MPN pathogenesis and drug-targeted therapy.