Objective:To investigate the specific mechanisms underlying the protective effect of interleukin (IL) -27 in the pathogenesis of psoriasis.Methods:Five skin tissue samples from healthy individuals and 6 lesional skin samples from psoriasis patients were collected, and IL-27 expression was determined by immunohistochemical staining. Il27ra gene knockout (KO) mice were constructed. Psoriasis-like mouse models were established with topical imiquimod in 5 wild-type (WT) mice and 6 KO mice. Mouse skin lesions were evaluated using the modified Psoriasis Area and Severity Index (mPASI), and lesional skin tissues were collected for hematoxylin and eosin (HE) staining to observe changes in epidermal thickness. Single-cell suspensions were prepared with skin lesions and skin-draining lymph nodes of 4 WT mice and 3 KO mice, and changes in immune cells (including T cells, γδ T cells, and neutrophils) were analyzed using flow cytometry. Additionally, skin-draining lymph node cells were isolated from 9 normal WT mice, and IL-17A expression was stimulated using a T-cell receptor agonist (CD3/28 activating antibodies, αCD3/28) or cytokines (IL-23 + IL-1β), followed by the addition of IL-27; peripheral blood mononuclear cells (PBMCs) were isolated from 6 psoriasis patients, and IL-17A expression was stimulated using the T-cell receptor agonist, followed by the addition of IL-27; the effect of IL-27 on IL-17A expression in T cells was analyzed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). Measurement data were compared between two groups using the t test. Results:Immunohistochemical staining revealed a significant reduction in IL-27 expression in psoriatic lesions (mean fluorescence intensity: 9.85 ± 3.07) compared with the normal skin (19.45 ± 2.51, t = 5.60, P < 0.001). Animal experiments demonstrated that the KO mice exhibited significantly aggravated psoriasis-like skin inflammation (mPASI: 4.00 ± 0.89) and significantly increased epidermal thickness (115.50 ± 7.69 μm) compared with the WT mice (mPASI: 2.80 ± 0.84, t = 2.28, P = 0.049; epidermal thickness: 92.26 ± 8.76 μm, t = 4.70, P = 0.001) ; compared with the WT mice, the KO mice showed significantly increased proportions of T cells (11.22% ± 2.76% vs. 7.08% ± 0.85%) and dermal γδ T cells (4.78% ± 0.39% vs. 2.78% ± 0.49%) among live cells in the lesions ( t = 2.91, 2.75, respectively, both P < 0.05), as well as significantly increased proportions of Th17, IL-17 + γδ T, Th22, and IL-22 + γδ T cells in the skin-draining lymph nodes (all P < 0.05), but no significant difference in the proportion of neutrophils in the lesions (WT: 13.57% ± 8.36%, KO: 14.43% ± 9.13%; t = 0.13, P = 0.902). Experiments with different stimuli showed that IL-27 significantly suppressed T-cell receptor agonist-induced IL-17A expression in murine γδ T cells (αCD3/28 group: 1.00 ± 0.11, αCD3/28 + IL-27 group: 0.76 ± 0.13; t = 3.54, P = 0.004), while there was no significant difference in IL-17A expression between cells induced by IL-23 + IL-1β with the IL-27 co-culture and those without ( t = 1.34, P > 0.05). ELISA showed that IL-27 significantly reduced the IL-17A concentration in the culture supernatant of draining lymph node cells stimulated by the T-cell receptor agonist (αCD3/28 group: 1 535.00 ± 97.76 pg/ml, αCD3/28 + IL-27 group: 1 030.00 ± 287.90 pg/ml, t = 3.29, P = 0.031), but did not reduce the IL-17A concentration induced by IL-23 + IL-1β ( t = 0.09, P > 0.05). Flow cytometry indicated that IL-27 significantly inhibited the T-cell receptor agonist-induced IL-17A expression in T cells from psoriasis patients (αCD3/28 group: 4.28 ± 3.25, αCD3/28 + IL-27 group: 3.04 ± 2.65, t = 4.46, P = 0.007) . Conclusion:IL-27 appeared to play a protective role in psoriasis by suppressing IL-17A secretion from T cells.

Objective:To explore and demonstrate the effect of general-specialty hierarchical management mode for chronic heart failure (CHF) in community.Methods:This was a single-blind, randomized, controlled study. A total of 530 CHF inpatients who attended Weifang Community Health Service Center (WCHSC) in Pudong New Area from February 2018 to September 2019 were consecutively enrolled. A random number table method was used to divide the patients into the management group ( n=265) and control group ( n=265). The demographic data and past medical history were collected 1 day before enrolment (baseline), and patients were assessed for New York Heart Association (NYHA) cardiac function classification and tested for blood N-terminal B-type natriuretic peptide proteins (NT-proBNP) levels, while Doppler echocardiography was performed to obtain the relevant indexes. The management group used a comprehensive management mode, co-delivered by both WCHSC (offering primary care) and RHSJUSM (offering specialty care) at Renji-Weifang CHF Studio in WCHSC , using the jointly developed CHF hierarchical CHF diagnosis and treatment criteria and referral procedure under the condition of sharing drugs and laboratory test results for CHF. The control group received routine heart failure care. Intergroup comparisons were made on baseline data obtained before follow-up and on NT-proBNP , left ventricular ejection fraction (LVEF), NYHA functional class , re-hospitalization rate and mortality rate at the end of the 6-month follow-up. Results:A total of 506 cases completed the follow-up. There were 253 patients in the management group, aged (68.26±9.41) years, 117 males (46.2%); 253 were in the control group, aged (66.98±9.63) years, 115 males (45.5%). There were no statistically significant differences in age, sex, marital status, education level, and comorbidities between the two groups (all P>0.05). At baseline, the differences in LVEF and NT-proBNP between the two groups were not statistically significant (all P>0.05), and at 6 months of intervention, LVEF, and NT-proBNP had significantly improved in both groups (all P<0.05) . Moreover, LVEF was higher in the management group than in the control group, and NT-proBNP was lower than in the control group (both P<0.01). At baseline, there were 166 cases (65.6%) in the control group with NYHA class Ⅲ/Ⅳ, and 145 cases (57.3%) in the comprehensive management group. There was no statistically significant difference between the two groups ( P>0.05). At 6 months of intervention, the percentage of NYHA class Ⅲ/Ⅳ patients in the comprehensive management group was lower than at baseline ( P<0.01),while that in the control group was higher than at baseline ( P<0.01), and the comprehensive management group was lower than that in the control group ( P<0.01). During the follow-up period, the rehospitalization rate for CHF in the management group was 13.83%(35/253), which was lower than that in the control group, which was 26.88%(68/253) ( P<0.001). Conclusion:The comprehensive management mode of CHF in the community through collaboration between general and specialized departments can significantly improve the management effect, suggesting that this mode is effective and can be promoted.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

ObjectiveThe U6 promoter is an essential element for driving sgRNA expression in the clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9（CRISPR/Cas9）gene editing system in dicotyledonous plants. Endogenous U6 promoters typically exhibit higher transcriptional activity， which can significantly improve gene editing efficiency. This study aims to identify endogenous U6 promoters in Artemisia annua to optimize its CRISPR/Cas9 gene editing system， which holds significant importance for its molecular breeding. MethodsOn the basis of the highly conserved U6 snRNA sequences in Arabidopsis thaliana， endogenous U6 promoters were screened in the A. annua genome. Expression vectors were constructed with candidate AaU6 promoter driving the firefly luciferase （LUC） reporter gene， and then transiently transformed into Nicotiana benthamiana. Transcriptional activities of the promoters were measured and compared by in vivo imaging and the Dual Luciferase Reporter assay. ResultsEight endogenous U6 promoters were successfully cloned from A. annua. Sequences alignment revealed that all these promoters contained the two conserved cis-acting elements， upstream sequence element （USE） and TATA-box， which affected their transcriptional activity. Dual-luciferase activity assays indicated that the transcriptional activities of AaU6-3， AaU6-1， and AaU6-5 were significantly higher than that of the Arabidopsis AtU6-26 promoter， with AaU6-3 exhibiting the highest activity. ConclusionThis study identified three endogenous AaU6 promoters with high transcriptional activity in A. annua， providing key functional elements for establishing an efficient gene editing system in A. annua. These findings will contribute to advancing precision molecular breeding and high-quality germplasm innovation in A. annua.

Objective:To investigate the specific mechanisms underlying the protective effect of interleukin (IL) -27 in the pathogenesis of psoriasis.Methods:Five skin tissue samples from healthy individuals and 6 lesional skin samples from psoriasis patients were collected, and IL-27 expression was determined by immunohistochemical staining. Il27ra gene knockout (KO) mice were constructed. Psoriasis-like mouse models were established with topical imiquimod in 5 wild-type (WT) mice and 6 KO mice. Mouse skin lesions were evaluated using the modified Psoriasis Area and Severity Index (mPASI), and lesional skin tissues were collected for hematoxylin and eosin (HE) staining to observe changes in epidermal thickness. Single-cell suspensions were prepared with skin lesions and skin-draining lymph nodes of 4 WT mice and 3 KO mice, and changes in immune cells (including T cells, γδ T cells, and neutrophils) were analyzed using flow cytometry. Additionally, skin-draining lymph node cells were isolated from 9 normal WT mice, and IL-17A expression was stimulated using a T-cell receptor agonist (CD3/28 activating antibodies, αCD3/28) or cytokines (IL-23 + IL-1β), followed by the addition of IL-27; peripheral blood mononuclear cells (PBMCs) were isolated from 6 psoriasis patients, and IL-17A expression was stimulated using the T-cell receptor agonist, followed by the addition of IL-27; the effect of IL-27 on IL-17A expression in T cells was analyzed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). Measurement data were compared between two groups using the t test. Results:Immunohistochemical staining revealed a significant reduction in IL-27 expression in psoriatic lesions (mean fluorescence intensity: 9.85 ± 3.07) compared with the normal skin (19.45 ± 2.51, t = 5.60, P < 0.001). Animal experiments demonstrated that the KO mice exhibited significantly aggravated psoriasis-like skin inflammation (mPASI: 4.00 ± 0.89) and significantly increased epidermal thickness (115.50 ± 7.69 μm) compared with the WT mice (mPASI: 2.80 ± 0.84, t = 2.28, P = 0.049; epidermal thickness: 92.26 ± 8.76 μm, t = 4.70, P = 0.001) ; compared with the WT mice, the KO mice showed significantly increased proportions of T cells (11.22% ± 2.76% vs. 7.08% ± 0.85%) and dermal γδ T cells (4.78% ± 0.39% vs. 2.78% ± 0.49%) among live cells in the lesions ( t = 2.91, 2.75, respectively, both P < 0.05), as well as significantly increased proportions of Th17, IL-17 + γδ T, Th22, and IL-22 + γδ T cells in the skin-draining lymph nodes (all P < 0.05), but no significant difference in the proportion of neutrophils in the lesions (WT: 13.57% ± 8.36%, KO: 14.43% ± 9.13%; t = 0.13, P = 0.902). Experiments with different stimuli showed that IL-27 significantly suppressed T-cell receptor agonist-induced IL-17A expression in murine γδ T cells (αCD3/28 group: 1.00 ± 0.11, αCD3/28 + IL-27 group: 0.76 ± 0.13; t = 3.54, P = 0.004), while there was no significant difference in IL-17A expression between cells induced by IL-23 + IL-1β with the IL-27 co-culture and those without ( t = 1.34, P > 0.05). ELISA showed that IL-27 significantly reduced the IL-17A concentration in the culture supernatant of draining lymph node cells stimulated by the T-cell receptor agonist (αCD3/28 group: 1 535.00 ± 97.76 pg/ml, αCD3/28 + IL-27 group: 1 030.00 ± 287.90 pg/ml, t = 3.29, P = 0.031), but did not reduce the IL-17A concentration induced by IL-23 + IL-1β ( t = 0.09, P > 0.05). Flow cytometry indicated that IL-27 significantly inhibited the T-cell receptor agonist-induced IL-17A expression in T cells from psoriasis patients (αCD3/28 group: 4.28 ± 3.25, αCD3/28 + IL-27 group: 3.04 ± 2.65, t = 4.46, P = 0.007) . Conclusion:IL-27 appeared to play a protective role in psoriasis by suppressing IL-17A secretion from T cells.

Objective:To explore and demonstrate the effect of general-specialty hierarchical management mode for chronic heart failure (CHF) in community.Methods:This was a single-blind, randomized, controlled study. A total of 530 CHF inpatients who attended Weifang Community Health Service Center (WCHSC) in Pudong New Area from February 2018 to September 2019 were consecutively enrolled. A random number table method was used to divide the patients into the management group ( n=265) and control group ( n=265). The demographic data and past medical history were collected 1 day before enrolment (baseline), and patients were assessed for New York Heart Association (NYHA) cardiac function classification and tested for blood N-terminal B-type natriuretic peptide proteins (NT-proBNP) levels, while Doppler echocardiography was performed to obtain the relevant indexes. The management group used a comprehensive management mode, co-delivered by both WCHSC (offering primary care) and RHSJUSM (offering specialty care) at Renji-Weifang CHF Studio in WCHSC , using the jointly developed CHF hierarchical CHF diagnosis and treatment criteria and referral procedure under the condition of sharing drugs and laboratory test results for CHF. The control group received routine heart failure care. Intergroup comparisons were made on baseline data obtained before follow-up and on NT-proBNP , left ventricular ejection fraction (LVEF), NYHA functional class , re-hospitalization rate and mortality rate at the end of the 6-month follow-up. Results:A total of 506 cases completed the follow-up. There were 253 patients in the management group, aged (68.26±9.41) years, 117 males (46.2%); 253 were in the control group, aged (66.98±9.63) years, 115 males (45.5%). There were no statistically significant differences in age, sex, marital status, education level, and comorbidities between the two groups (all P>0.05). At baseline, the differences in LVEF and NT-proBNP between the two groups were not statistically significant (all P>0.05), and at 6 months of intervention, LVEF, and NT-proBNP had significantly improved in both groups (all P<0.05) . Moreover, LVEF was higher in the management group than in the control group, and NT-proBNP was lower than in the control group (both P<0.01). At baseline, there were 166 cases (65.6%) in the control group with NYHA class Ⅲ/Ⅳ, and 145 cases (57.3%) in the comprehensive management group. There was no statistically significant difference between the two groups ( P>0.05). At 6 months of intervention, the percentage of NYHA class Ⅲ/Ⅳ patients in the comprehensive management group was lower than at baseline ( P<0.01),while that in the control group was higher than at baseline ( P<0.01), and the comprehensive management group was lower than that in the control group ( P<0.01). During the follow-up period, the rehospitalization rate for CHF in the management group was 13.83%(35/253), which was lower than that in the control group, which was 26.88%(68/253) ( P<0.001). Conclusion:The comprehensive management mode of CHF in the community through collaboration between general and specialized departments can significantly improve the management effect, suggesting that this mode is effective and can be promoted.

Objective:To analyze the intrauterine ultrasound manifestations and postnatal follow-up outcomes of fetuses with 2q13 microdeletion.Methods:This retrospective study involved 23 cases of 2q13 microdeletion, diagnosed via amniotic fluid chromosome karyotyping and single nucleotide polymorphism-array (SNP-array) following amniocentesis, between January 1, 2018, and September 1, 2022, at Wuxi Maternity and Child Health Care Hospital. Descriptive statistical analysis was applied to prenatal diagnostic indications, intrauterine ultrasound findings, prenatal diagnosis results, and postnatal follow-up outcomes.Results:(1) The prenatal diagnostic indications for the 23 cases of 2q13 microdeletion included seven cases (30.4%) of high-risk serological screening, six cases (26.1%) of increased nuchal translucency (NT), two cases (8.7%) of fetal heart defects, two cases (8.7%) of advanced maternal age, two cases (8.7%) of fetal choroid plexus cysts (one of which was also associated with high-risk serological screening), one case (4.3%) of suboptimal fetal nasal bone fusion, one case (4.3%) of non-invasive prenatal testing suggesting chromosomal abnormalities, one case (4.3%) of fetal obstructive polycystic kidneys, one case (4.3%) of fetal subependymal cysts, and one case (4.3%) of fetal growth restriction. (2) Intrauterine ultrasound findings included six cases (26.1%) of NT thickening, four cases (17.4%) of intrauterine growth restriction, two cases (8.7%) of fetal heart defects, two cases (8.7%) of choroid plexus cysts, one case (4.3%) of oligohydramnios, one case (4.3%) of suboptimal fetal nasal bone fusion, one case (4.3%) of short long bones in the fetus, one case (4.3%) of polyhydramnios with large fetal abdominal circumference, one case (4.3%) of large fetal abdominal circumference, short long bones, and subependymal cysts of the brain ventricles, and one case (4.3%) of fetal obstructive polycystic kidneys; the remaining six cases (26.1%) showed no abnormal ultrasound findings. (3) Chromosome karyotyping revealed three cases of chromosomal structural abnormalities, one case of sex chromosome numerical abnormalities, and the remaining 19 cases showed no abnormalities. Amniotic fluid SNP-array results indicated deletions ranging from 104 to 1 745 kb. Parental verification was performed in ten cases, showing maternal inheritance in four cases, paternal inheritance in five, and one case of a de novo mutation. (4) Four cases (17.4%) opted for pregnancy termination, while 19 cases (82.6%) resulted in live births. The 19 live-born children underwent telephone and child health follow-up, with ages at follow-up being 3 years (ranging from 9 to 58.8 months). Apart from two cases that did not undergo newborn congenital heart disease screening, the remaining 17 surviving infants were screened without any abnormalities. Five cases had abnormal growth and development during follow-up: one 18-month-old with mild language developmental delay, one 3-year-old plus 26 days with mild language developmental delay, one 18-month-old with language developmental delay, one 3-year-old with astigmatism, and one 30-month-old with refractive error in both eyes during a physical examination; the other 14 children showed no significant abnormalities in growth and development. Conclusions:The intrauterine ultrasound manifestations of fetuses with 2q13 microdeletion are non-specific, and most of them are inherited from their parents. Postnatal follow-up should pay attention to the development of the nervous system of children.

Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.
Humans ; Randomized Controlled Trials as Topic ; Acupuncture Therapy/methods* ; Pain ; Pain Management ; China

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.