OBJECTIVE To analyze clinical switching patterns and reasons between bevacizumab biosimilar and originator drugs. METHODS The data were collected from 1 175 cancer patients treated with bevacizumab at Ruijin Hospital， Shanghai Jiao Tong University School of Medicine from January 1， 2018， to December 31， 2023. The patients were divided into originator group （n＝250） and biosimilar group （n＝925）. The switching rate， switching type and reasons of the two groups were compared. RESULTS There were no statistically significant differences in the switching rate， switching types， and the number of switches between the two groups （P＞0.05）. Single， one-way switches were the switching type in both groups. The proportion of patients in the biosimilar group who switched due to adverse events was significantly higher than originator group， while the proportion of patients who switched due to treatment costs was significantly lower than originator group （P＜0.05）. There were no statistically significant differences in the proportions of patients who switched due to efficacy and drug accessibility between the two groups （P＞0.05）. CONCLUSIONS The switching between bevacizumab biosimilar and the originator drugs mainly involves single， one- way switches. Treatment costs and drug accessibility are the main factors for the switches among users of originator drugs， while drug accessibility and adverse events are the main factors for the switches among users of biosimilar.

Objective To explore the evaluation on the curative effect of digital subtraction angiography(DSA)-guided radiofrequency ablation in patients with lumbar disc herniation(LDH)based on infrared thermal imaging technology.Methods A total of 90 patients with LDH treated in the hospital were enrolled as the research objects between February 2019 and February 2022.According to different treatment methods,they were divided into observation group(n=45)and control group(n=45).The control group was treated with radiofrequency ablation,while observation group was treated with DSA-guided radiofrequency ablation.The scores of visual analogue scale(VAS),Oswestry disability index(ODI)and Japanese Orthopaedic Association(JOA),and levels of serologic indexes[interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]were compared between the two groups before treatment and at 1 month and 3 months after treatment.The skin temperature of lesions was detected by infrared thermal imaging,and its correlation with VAS,ODI and JOA scores was analyzed by Pearson correlation analysis.Results Before treatment,there was no significant difference in VAS score between the two groups(P＞0.05).At 1 month and 3 months after treatment,VAS scores in both groups were decreased,which were lower in observation group than control group(P＜0.05).Before treatment,there was no significant difference in ODI and JO A scores between the two groups(P＞0.05).At 1 month and 3 months after treatment,ODI scores in both groups were decreased,which were lower in observation group than control group,while JOA scores were increased,which were higher in observation group than control group(P＜0.05).Before treatment,there was no significant difference in levels of serum IL-1β,IL-6 and TNF-α between the two groups(P＞0.05).At 1 month and 3 months after treatment,levels of serum IL-1 β,IL-6 and TNF-α in both groups were decreased,which were lower in observation group than control group(P＜0.05).Before treatment,there was no significant difference in skin temperature of lesions between the two groups(P＞0.05).At 1 month and 3 months after treatment,skin temperature of lesions in both groups was decreased,which was lower in observation group than control group(P＜0.05).Pearson correlation analysis showed that skin temperature of lesions was positively correlated with VAS,ODI and JOA scores at 1 month and 3 months after treatment(r=0.455,0.502,0.523,0.675,0.659,0.611,P＜0.05).Conclusion Curative effect of DSA-guided radiofrequency ablation is good on LDH patients,and infrared thermal imaging can effectively evaluate the curative effect.

Incarvillea younghusbandii Sprague is a traditional tonic herb. The roots are used as herbal medicine for nourishing and strengthening, as well as treating postpartum milk deficiency and weakness. In this study, the chloroplast genome of I. younghusbandii was sequenced and assembled by the high-throughput sequencing technology. The sequence characteristics, sequence repeats, codon usage bias, phylogenetic relationships and estimated divergence time of I. younghusbandii were analyzed. The 159 323 bp sequence contained a large single copy (80 197 bp), a small single copy (9 030 bp) and two inverted repeat sequences (35 048 bp). It contained 120 genes, including 77 protein coding genes, 8 ribosomal RNA genes and 35 transfer RNA genes. AAA was the most frequent codon in the chloroplast coding sequence of I. younghusbandii. A total of 42 simple sequence repeats were identified in the chloroplast genome. Phylogenetic analysis revealed I. younghusbandii was mostly like its taxonomically close relative Incarvillea compacta. The divergence between I. younghusbandii and I. compacta was dated to 4.66 million years ago. This study was significant for the scientific conservation and development of resources related to I. compacta. It also provides a basic genetic resource for the subsequent species identification of the genus Incarvillea, and the population genetic diversity study of Bignoniaceae.
Phylogeny ; Molecular Sequence Annotation ; Genome, Chloroplast ; Sequence Analysis, DNA ; Whole Genome Sequencing

Objective: To examine the clinical efficacy of 3 anti-reflux methods of digestive tract reconstruction after proximal gastrectomy for gastric cancer. Methods: The clinical data and follow-up data of gastric cancer patients who underwent anti-reflux reconstruction after proximal gastrectomy in 11 medical centers of China from September 2016 to August 2021 were retrospectively collected, including 273 males and 65 females, aging of (63±10) years (range: 28 to 91 years). Among them, 159 cases were performed with gastric tube anastomosis (GTA), 107 cases with double tract reconstruction (DTR), and 72 cases with double-flap technique (DFT), respectively. The duration of operation, length of postoperative hospital stay and early postoperative complications (referring to Clavien-Dindo classification) of different anti-reflux reconstruction methods were assessed. Body mass index, hemoglobin and albumin were used to reflect postoperative nutritional status. Reflux esophagitis was graded according to Los Angeles criteria based on the routinely gastroscopy within 12 months after surgery. The postoperative quality of life (QoL) was evaluated by Visick score system. The ANOVA analysis, Kruskal-Wallis rank sum test, χ² test and Fisher's exact test were used for comparison between multiple groups, and further comparison among groups were performed with LSD, Tamhane's test or Bonferroni corrected χ² test. The mixed effect model was used to compare the trends of Body mass index, hemoglobin and albumin over time among different groups. Results: The operation time of DFT was significantly longer than that of GTA and DTR ((352±63) minutes vs. (221±66) minutes, (352±63) minutes vs. (234±61) minutes, both P<0.01). The incidence of early complications with Clavien-Dindo grade Ⅱ to Ⅴ in GTA, DFT and DTR groups was 17.0% (27/159), 9.7% (7/72) and 10.3% (11/107), respectively, without significant difference among these three groups (χ²=3.51, P=0.173). Body mass index decreased more significantly in GTA than DFT group at 6 and 12 months after surgery (mean difference=1.721 kg/m², P<0.01; mean difference=2.429 kg/m², P<0.01). body mass index decreased significantly in DTR compared with DFT at 12 months after surgery (mean difference=1.319 kg/m², P=0.027). There was no significant difference in hemoglobin or albumin fluctuation between different reconstruction methods perioperative. The incidence of reflux esophagitis one year after surgery in DTR group was 12.9% (4/31), which was lower than that in DFT (45.9% (17/37), χ²=8.63, P=0.003). Follow-up of postoperative quality of life showed the incidence of Visick grade 2 to 4 in DFT group was lower than that in GTA group (10.4% (7/67) vs. 34.6% (27/78), χ²=11.70, P=0.018), while there was no significant difference between DFT and DTR group (10.4% (7/67) vs. 22.2% (8/36, P>0.05). Conclusions: Compared with GTA and DTR, DFT is more time-consuming, but there is no significant difference in early complications among three methods. DFT reconstruction is more conducive to maintain postoperative nutritional status and improve QoL, especially compared with GTA. The risk of reflux esophagitis after DTR reconstruction is lower than that of DFT.
Aged ; Albumins ; Esophagitis, Peptic/surgery* ; Female ; Gastrectomy/methods* ; Hemoglobins ; Humans ; Male ; Middle Aged ; Quality of Life ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Three new ursane-type triterpenoids, 3-oxours-12-en-20, 28-olide (1), 3β-hydroxyurs-12-en-20, 28-olide (2) and 3β-hydroxyurs-11, 13(18)-dien-20, 28-olide (3), were isolated from a potent anti-inflammatory and antibacterial fraction of the ethanolic extract of Rosmarinus officinalis. Their structures were elucidated by a combination of extensive 1D- and 2D-NMR experiments, MS data and comparisons with literature reports. Compounds 1-3 exhibited significantly inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages, but no antibacterial activity was found at a concentration of 128 μg·mL^-1.
Animals ; Drugs, Chinese Herbal/chemistry* ; Mice ; Molecular Structure ; Rosmarinus ; Triterpenes/chemistry*

Lithium carbonate as a mood stabilizer ，is the first -line treatment for bipolar disorder （BD）. Due to the narrow treatment range and large individual respons e differences ，physiological and pathological states and drug interactions can affect its therapeutic effect ；as therapeutic drug monitoring （TDM），population pharmacokinetics （PPK）and pharmacogenomics play an increasingly important role in the individualized use of lithium carbonate ，how to optimize the individualized use of lithium carbonate more effectively has attracted much attention . This paper reviewed the latest research progress of TDM ，PPK and pharmacogenomics in the individualized treatment of lithium carbonate in recent years . Due to the influence of patients ’ pathophysiological status ，the target blood concentration range of lithium among different populations was slightly different . To ensure its efficacy and safety ，routine TDM was required . PPK studies conducted in different populations showed that the relevant predictors used to optimize lithium treatment included body mass ，lean body mass ，age and renal function ，etc. Pharmacogenomics research showed that the single nucleotide polymorphisms of FKBP5，ACP1，ADCY2 and other genes were related to the difference of patients ’treatment response . Therefore，on the basis of routine TDM for lithium carbonate ，the comprehensive evaluation combined with PPK and pharmacogenomics is of great significance for the individual treatment of lithium carbonate .

The molecular identification of Fritillaria taibaiensis and its relatives was studied by real-time PCR with a TaqMan-MGB probe. DNA was extracted from F. taibaiensis and its relatives. According to the sequence of ITS1 region, the mutation sites of F. taipaiensis and its related species were identified by MEGA7.0 software. The specific primers (a pair) and a TaqMan-MGB probe were designed by Primer Premier 6.0 software. In the Roche LightCycler 96 system, the lowest limit of detection for F. taipaiensis DNA template was 0.002 39 ng·μL^-1, and the optimal T_m value range was 60 and 61 ℃. Specificity identification showed that the method had good specificity for F. taipaiensis, as it could be distinguished from other 13 different Fritillaria species including F. unibracteata. Since this method could accurately identify F. taipaiensis and its related species, it provides technical support for rational development of F. taipaiensis resources, management of Chinese medicinal market and supervision of raw materials in Chinese medicine manufacturing enterprises.

Aim To study the protective effect of proanthocyanidins extracted from Rubus amabilis Focke (RPC) on the pancreatic tissues of diabetic mice and the underlying mechanism. Methods C57BL/6 male mice were given a high-sugar and high-fat diet combined with an intraperitoneal injection of STZ to establish the diabetic model. The mice whose FBG were higher than 16. 7 mmol · L

The radiation is regarded as the fourth biggest pollution following the water, air and noise pollution, which generates a broad impact on human physiology and healthy. The radiation mainly comes from medical rays, industrial rays, nuclear wastes and atmospheric ultraviolet rays. The universality makes people pay more and more attention to the damage effect and mechanism of radiation. The radiation is divided into ionizing and non-ionizing radiation. It is a good idea to study the effect of ionizing and non-ionizing radiation on drug's metabolism, which may give a guidance to clinical medication to avoid adverse reactions and to support personalized medicine. This article reviews the effect of ionizing radiation (γ-rays, X-rays, uranium and cesium) and non-ionizing radiation (ultraviolet rays) on drug metabolism, their impact on metabolic characteristics of some drugs and the impact on expression of enzymes and transporters in drug metabolism, which is conducted with a focus on clinical significance.