Objective To observe the effects of acupuncture at acupoints along the meridians on the expression of frontal lobe associated protein kinase in pchlorophenylalanine(PCPA)induced insomnia rats;To explore the mechanism of acupuncture in improving insomnia.Methods Totally 60 rats were randomly divided into blank group,model group,sham acupuncture group,acupuncture group and Western medicine group,with 12 rats in each group.An insomnia model rat was induced by intraperitoneal injection of PCPA.The acupuncture group received acupuncture at"Baihui","Shenmen"(bilateral),and"Sanyinjiao"(bilateral),while the sham acupuncture group only fixed the needle at the corresponding acupoints but did not penetrate the skin,while the model group was only fixed for 30 minutes,the Western medicine group was given a solution of estazolam by gavage for 7 consecutive days,the blank group was not treated.The pentobarbital sodium reversal experiment was used to detect the sleep latency and sleep time of rats,ELISA was used to detect the content of melatonin(MT)in plasma,RT-PCR was used to detect the mRNA expressions of calmodulin dependent protein kinase(CaMK)Ⅱ,protein kinase C(PKC)and p38 mitogen activated protein kinase(MAPK)in frontal lobe tissue,and Western blot was used to detect the protein expressions of CaMKⅡ,PKC and p38MAPK in frontal lobe tissue.Results Compared with the blank group,the sleep latency of the model group rats were significantly prolonged and the sleep time were significantly shortened(P<0.01),the content of MT in plasma was significantly reduced(P<0.01),and the mRNA and protein expressions of CaMKⅡ and PKC in frontal lobe tissue were significantly decreased(P<0.01),the mRNA and protein expressions of p38MAPK were significantly increased(P<0.01).Compared with the model group,the sleep latency were significantly shortened and the sleep time were significantly prolonged in the acupuncture group and the Western medicine group(P<0.01),the plasma MT content significantly increased(P<0.01),the mRNA and protein expressions of CaMKⅡ and PKC in frontal lobe tissue significantly increased(P<0.05),and the mRNA and protein expression of p38MAPK significantly decreased(P<0.01).Compared with the sham acupuncture group,the sleep latency shortened and sleep time were significantly prolonged in the acupuncture group and the Western medicine group(P<0.01),plasma MT content significantly increased(P<0.01),PKC mRNA expression in frontal lobe tissue significantly increased(P<0.01),and p38MAPK mRNA expression significantly decreased(P<0.01).There was no statistically difference in various indicators between the acupuncture group and the Western medicine group(P>0.05).Conclusion Acupuncture at acupoints along the meridians can shorten the sleep latency and prolong sleep time,improve sleep status by regulating the expression of associated protein kinase in frontal lobe of insomnia rats.

Objective:To investigate the correlation of antinuclear antibody (ANA) with clinical response to infliximab (IFX) in patients with Crohn′s disease (CD) .Methods:Patients who were diagnosed as CD and treated with IFX in Nanjing Drum Tower Hospital from January 2018 to September 2021 were retrospectively studied. The correlation analysis was used to explore the correlation between ANA and clinical response. These patients were divided into two groups according to the ANA titer after 25 weeks of IFX treatment. The differences in clinical data between the two groups were assessed by univariate analysis. The variables with P<0.15 in univariate analysis and having clinical significance were further analyzed by multivariate Logistic regression to determine the independent risk factors of the induction of ANA. Results:A total of 82 patients with CD were included. Forty-one (50.0%) patients were set as positive group, and 41 (50.0%) patients were set as negative group. In terms of clinical response, the clinical response rates of two groups were 68.3% and 41.5%, and the difference was significant (χ 2 = 5.959, P = 0.015) . Positive group was divided into 1∶100 subgroup ( n = 17) , 1∶320 subgroup ( n = 11) and ≥1∶1000 subgroup ( n = 13) . The clinical response rates of three groups were 41.2%, 45.5% and 7.7% respectively, and the difference was not statistically significant (χ 2 = 5.334, P = 0.084) . The incidences of adverse events in the two groups were 17.1% and 7.3%, and the difference was not significant (χ 2 = 1.822, P = 0.177) . Univariate analysis showed that the difference of total protein (TP) before IFX treatment between the positive group and negative group was statistically significant ( P<0.05) . Multivariate logistic regression analysis showed that age ( OR = 1.060, 95% CI: 1.015 ~ 1.107, P = 0.008) and the baseline TP ( OR = 1.110, 95% CI: 1.023 ~ 1.205, P = 0.012) were the independent risk factors for the induction of ANA. Conclusions:The formation of ANA may affect the clinical response of IFX, so the ANA titer should be monitored regularly during the IFX therapy. In addition, age and baseline TP are related to the formation of ANA.

Objective:To investigate the correlation of antinuclear antibody (ANA) with clinical response to infliximab (IFX) in patients with Crohn′s disease (CD) .Methods:Patients who were diagnosed as CD and treated with IFX in Nanjing Drum Tower Hospital from January 2018 to September 2021 were retrospectively studied. The correlation analysis was used to explore the correlation between ANA and clinical response. These patients were divided into two groups according to the ANA titer after 25 weeks of IFX treatment. The differences in clinical data between the two groups were assessed by univariate analysis. The variables with P<0.15 in univariate analysis and having clinical significance were further analyzed by multivariate Logistic regression to determine the independent risk factors of the induction of ANA. Results:A total of 82 patients with CD were included. Forty-one (50.0%) patients were set as positive group, and 41 (50.0%) patients were set as negative group. In terms of clinical response, the clinical response rates of two groups were 68.3% and 41.5%, and the difference was significant (χ 2 = 5.959, P = 0.015) . Positive group was divided into 1∶100 subgroup ( n = 17) , 1∶320 subgroup ( n = 11) and ≥1∶1000 subgroup ( n = 13) . The clinical response rates of three groups were 41.2%, 45.5% and 7.7% respectively, and the difference was not statistically significant (χ 2 = 5.334, P = 0.084) . The incidences of adverse events in the two groups were 17.1% and 7.3%, and the difference was not significant (χ 2 = 1.822, P = 0.177) . Univariate analysis showed that the difference of total protein (TP) before IFX treatment between the positive group and negative group was statistically significant ( P<0.05) . Multivariate logistic regression analysis showed that age ( OR = 1.060, 95% CI: 1.015 ~ 1.107, P = 0.008) and the baseline TP ( OR = 1.110, 95% CI: 1.023 ~ 1.205, P = 0.012) were the independent risk factors for the induction of ANA. Conclusions:The formation of ANA may affect the clinical response of IFX, so the ANA titer should be monitored regularly during the IFX therapy. In addition, age and baseline TP are related to the formation of ANA.

Objective:To explore forecast indicators for the prognosis of sepsis in adult extremely severe burn patients.Methods:Case data of adults with extremely severe burns combined with sepsis admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2021 were retrospectively collected. According to the prognosis, all patients were divided into a death group and a survival group. The general conditions of the two groups were compared. The clinical symptoms, vital signs, platelet count (PLT), white blood cell count (WBC), neutrophil ratio, procalcitonin (PCT), blood sodium, blood glucose, hemoglobin and albumin levels at diagnosis of sepsis were also compared between the two groups. The independent sample t test, Mann?Whitney U test, or Fisher's exact probability test was used for group comparison. Variables with statistical significance in univariate analysis were included in the Cox regression model for multivariate analysis to assess the effect of each index on the outcome of extremely severe burn patients with sepsis. The predictive value of each index for sepsis outcome was analyzed by the receiver operating characteristic curve (ROC). Results:A total of 60 patients with particularly severe burn sepsis were selected, including 41 males and 19 females aged 18 to 84 years. The diagnosis time of sepsis was 14 (7, 24) days after injury. There were 29 patients in the death group and 31 patients in the survival group, and the mortality rate was 48.3%. Compared with the survival group, PLT and hemoglobin levels in the death group decreased significantly (both P<0.05), and PCT and blood sodium levels increased significantly (both P<0.05), while the other indicators did not change significantly (all P>0.05). The results of multivariate Cox regression analysis showed that hemoglobin ( HR=0.936, 95% CI: 0.935-0.991) and serum sodium levels ( HR=1.031, 95% CI: 1.010-1.052) at the time of sepsis diagnosis were independent risk factors affecting the prognosis of sepsis in extra-severe burn patients (both P<0.05). ROC curve analysis showed that the AUCs of hemoglobin, blood sodium and PCT for predicting the prognosis of extremely severe burn patients with sepsis were 0.747, 0.811 and 0.690, respectively (all P<0.05). The cut-off value of hemoglobin for predicting prognosis was 77 g/L, with a sensitivity of 69.0% and specificity of 74.2%. The cut-off value of blood sodium for predicting prognosis was 138 mmol/L, with a sensitivity of 89.7% and specificity of 61.3%. The cut-off value of PCT was 3.51 μg/L, with a sensitivity of 65.5% and specificity of 74.2%. Conclusions:Hemoglobin, blood sodium and PCT may be predictors of outcome in extremely severe burn patients with sepsis.

In order to address the issues of spatial induction bias and lack of effective representation of global contextual information in colon polyp image segmentation, which lead to the loss of edge details and mis-segmentation of lesion areas, a colon polyp segmentation method that combines Transformer and cross-level phase-awareness is proposed. The method started from the perspective of global feature transformation, and used a hierarchical Transformer encoder to extract semantic information and spatial details of lesion areas layer by layer. Secondly, a phase-aware fusion module (PAFM) was designed to capture cross-level interaction information and effectively aggregate multi-scale contextual information. Thirdly, a position oriented functional module (POF) was designed to effectively integrate global and local feature information, fill in semantic gaps, and suppress background noise. Fourthly, a residual axis reverse attention module (RA-IA) was used to improve the network's ability to recognize edge pixels. The proposed method was experimentally tested on public datasets CVC-ClinicDB, Kvasir, CVC-ColonDB, and EITS, with Dice similarity coefficients of 94.04%, 92.04%, 80.78%, and 76.80%, respectively, and mean intersection over union of 89.31%, 86.81%, 73.55%, and 69.10%, respectively. The simulation experimental results show that the proposed method can effectively segment colon polyp images, providing a new window for the diagnosis of colon polyps.
Humans ; Colonic Polyps/diagnostic imaging* ; Computer Simulation ; Electric Power Supplies ; Semantics ; Image Processing, Computer-Assisted

Objective:To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Objective:To investigate the incidence, clinical characteristics and risk factors of growth retardation in pediatric onset IBD patients.Methods:A cross-sectional study was conducted. IBD patients with the age at diagnosis younger than 18 years old were recruited and screened in the Wechat group of patients in 8 IBD medical centers across the country. Demographic, clinical and growth-related data were collected through questionnaire survey, and the incidences of growth retardation at the time of diagnosis and investigation were calculated. According to whether there was growth retardation at the time of investigation, the patients were divided into growth retardation group and non-growth retardation group. The influencing factors of growth retardation were analyzed by the univariate analysis and multivariate Logistic regression analysis.Results:A total of 97 patients were involved including 8 ulcerative colitis (UC) and 89 Crohn′s disease (CD). There was no growth retardation in UC patients. Among 89 patients with CD, there were 48 males and 41 females, and the age was 15.5 (1.0, 21.0) years old. At the time of investigation, 14 patients (15.7%) with growth retardation were set as the growth retardation group, and 75 without growth retardation were set as the non-growth retardation group. The incidence of growth retardation was 19.0% (16/84) at the time of diagnosis. Univariate analysis results showed that compared with non-growth retardation group, patients in growth retardation group had lower diagnostic age [5.0 (1.0, 13.8) years old vs. 14.0 (12.0, 16.0) years old, P = 0.003], severer disease activity ( P = 0.006), higher proportion of acute gastrointestinal perforation [28.6% (4/14) vs. 2.7% (2/75), P = 0.005], higher proportion of patients in using glucocorticoids [64.3% (9/14) vs. 33.3% (25/75), P = 0.029), and longer time of using glucocorticoids [1.5 (0, 6.5) months vs. 0 (0, 3.0) months, P = 0.040], while the proportion of patients using biological agents was lower [42.9% (6/14) vs. 80.0% (60/75), P = 0.010], and the time of using biological agents was shorter [0 (0, 6.3) months vs. 7.0 (1.0, 12.0) months, P = 0.006]. Logistic regression analysis revealed that the age at diagnosis of CD was still a risk factor for growth retardation after correcting other factors ( OR = 6.909, 95% CI: 1.250-38.195, P = 0.027) . Conclusion:The pediatric onset IBD patients with low diagnostic age are prone to growth retardation, which should be paid attention to.

Objective:To explore the value of biphasic quantitative CT on small airway disease and emphysema injury in patients with smoking combined with chronic obstructive pulmonary disease (COPD).Methods:A total of 186 male physical examination subjects who underwent biphasic CT and pulmonary function (PFT) examinations in the Affiliated Hospital of Yan′an University from July 2018 to September 2020 were enrolled in this retrospective study. These subjects were divided into 121 smokers with COPD (COPD group), aged 34 to 84 (64±8) years old and 65 smokers without COPD (non-COPD group) aged 34 to 72 (61±5) years old. According to the guidelines of the COPD global initiative, patients in COPD group were divided into Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) Ⅰ-Ⅳ grades. The original DICOM data of CT were imported into the "Digital Lung" test and analysis platform. Quantitative parameters of functional small airway disease percentage (fSAD%) and emphysema area percentage (Emph%) of each lobe were calculated. The differences of CT quantitative parameters among non-COPD group and each grade in COPD group were analyzed by One-Way ANOVA or Kruskal-Wallis H test. The correlation between the smoking index and CT quantitative parameters was analyzed by Spearman correlation analysis. Results:There were significant differences in fSAD% and Emph% of each lobe among non-COPD group and COPD group GOLD Ⅰ-Ⅳ ( P<0.001). Except that the Emph% in right middle lobe of GOLD grade Ⅰ was higher than that of GOLD grade Ⅱ in COPD group, the fSAD% and Emph% in other lobes increased gradually with the increase of GOLD grade in COPD group. The fSAD% and Emph% were larger in the right middle lobe and both upper lobes of COPD group GOLD Ⅰ-Ⅳ. The comparison among each lobe showed that the differences were statistically significant ( P<0.01), except for the fSAD% and Emph% of GOLD Ⅳ ( P=0.395, 0.840). The smoking index was positively correlated with fSAD% and Emph% in each lung lobe. Among them, smoking index was highly correlated with fSAD% in the lower right lobe and Emph% in the lower left lobe ( r=0.474, 0.619, P<0.001). Conclusion:The biphasic quantitative CT can early and sensitively reflect the degree of small airway disease and emphysema injury in smoking combined with COPD, which is of great significance for the early diagnosis and evolution of COPD.

Tetrapyrrole compounds are a class of compounds with important functions. They exist in living organisms and have been widely used in agriculture, food, medicine, and other fields. The cumbersome process and high cost of chemical synthesis, as well as the shortcomings of unstable quality of animal and plant extraction methods, greatly hampered the industrial production and applications of tetrapyrrole compounds. In recent years, the rapid development of synthetic biology has provided new tools for microorganisms to efficiently synthesize tetrapyrrole compounds from renewable biomass resources. This article summarizes various strategies for the biosynthesis of tetrapyrrole compounds, discusses methods to improve its biosynthesis efficiency and future prospects, with the aim to facilitate the research on biosynthesis of tetrapyrrole compounds.
Biomass ; Plants/genetics* ; Synthetic Biology ; Tetrapyrroles

Objective:To investigate the incidence, clinical characteristics and risk factors of growth retardation in pediatric onset IBD patients.Methods:A cross-sectional study was conducted. IBD patients with the age at diagnosis younger than 18 years old were recruited and screened in the Wechat group of patients in 8 IBD medical centers across the country. Demographic, clinical and growth-related data were collected through questionnaire survey, and the incidences of growth retardation at the time of diagnosis and investigation were calculated. According to whether there was growth retardation at the time of investigation, the patients were divided into growth retardation group and non-growth retardation group. The influencing factors of growth retardation were analyzed by the univariate analysis and multivariate Logistic regression analysis.Results:A total of 97 patients were involved including 8 ulcerative colitis (UC) and 89 Crohn′s disease (CD). There was no growth retardation in UC patients. Among 89 patients with CD, there were 48 males and 41 females, and the age was 15.5 (1.0, 21.0) years old. At the time of investigation, 14 patients (15.7%) with growth retardation were set as the growth retardation group, and 75 without growth retardation were set as the non-growth retardation group. The incidence of growth retardation was 19.0% (16/84) at the time of diagnosis. Univariate analysis results showed that compared with non-growth retardation group, patients in growth retardation group had lower diagnostic age [5.0 (1.0, 13.8) years old vs. 14.0 (12.0, 16.0) years old, P = 0.003], severer disease activity ( P = 0.006), higher proportion of acute gastrointestinal perforation [28.6% (4/14) vs. 2.7% (2/75), P = 0.005], higher proportion of patients in using glucocorticoids [64.3% (9/14) vs. 33.3% (25/75), P = 0.029), and longer time of using glucocorticoids [1.5 (0, 6.5) months vs. 0 (0, 3.0) months, P = 0.040], while the proportion of patients using biological agents was lower [42.9% (6/14) vs. 80.0% (60/75), P = 0.010], and the time of using biological agents was shorter [0 (0, 6.3) months vs. 7.0 (1.0, 12.0) months, P = 0.006]. Logistic regression analysis revealed that the age at diagnosis of CD was still a risk factor for growth retardation after correcting other factors ( OR = 6.909, 95% CI: 1.250-38.195, P = 0.027) . Conclusion:The pediatric onset IBD patients with low diagnostic age are prone to growth retardation, which should be paid attention to.