The main active compound, 3,4-dihydroxyacetophenone(3,4-DHAP), in the leaves of Ilex pubescens var. glaber, exhibits various pharmacological activities, including vasodilation and heart protection. Currently, natural extraction and chemical synthesis are the primary methods for obtaining 3,4-DHAP, but both approaches have inherent challenges. To address these problems, this study explored the whole-cell bioconversion of 1-(4-hydroxyphenol)-ethanol to 3,4-DHAP using recombinant Escherichia coli, cultivated in a green, cost-effective medium at room temperature and atmospheric pressure. Firstly, this study successfully constructed recombinant E. coli S1, which contained only the HpaBC gene, and recombinant E. coli S3, which contained both the Hped and HpaBC genes. The ability of S1 and S3 to synthesize 3,4-DHAP from their respective substrates was then evaluated through whole-cell bioconversion. Based on these results, the effects of four factors, i.e., substrate concentration, IPTG concentration, induction temperature, and transformation temperature, on the whole-cell bioconversion yield of S3 were investigated using an orthogonal experiment. The results showed that the factors influenced the yield in the following order: transformation temperature > induction temperature > IPTG concentration > substrate concentration. The optimal conditions were found to be a transformation temperature of 35 ℃, IPTG concentration of 0.1 mmol·L~(-1), induction temperature of 25 ℃, and substrate concentration of 10 mmol·L~(-1). Finally, the effect of transformation time on the yield of 3,4-DHAP was further examined under the optimal conditions. The results indicated that as the transformation time increased, the yield of 3,4-DHAP steadily increased. The highest yield of 260 mg·L~(-1) with a productivity of 17% was achieved after 72 hours of transformation. In conclusion, this study successfully achieved the whole-cell bioconversion of 1-(4-hydroxyphenol)-ethanol to 3,4-DHAP using recombinant E. coli for the first time, laying the groundwork for further optimization and development of the biosynthesis of 3,4-DHAP.
Escherichia coli/genetics* ; Acetophenones/chemistry* ; Ethanol/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Biotransformation

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

Objective:To investigate the association between visceral adipose tissue (VAT) thickness in early pregnancy and the risk of gestational diabetes mellitus (GDM).Methods:Based on the Qingdao Women and Children Health Cohort, pregnant women in the first trimester (11-13 +6 weeks of gestation) were enrolled in this cohort study between May 2019 and October 2022. The VAT was measured in first trimester and determined as the distance from the inner margin of the rectus abdominis muscle to the anterior wall of the great artery using multi-functional color ultrasound. The 75 g oral glucose tolerance test (OGTT) results were followed up at 24-28 weeks and the participants were divided into GDM group and non-GDM group. The pregnant women were divided into 4 groups according to the VAT quartile. Log-binomial model and linear regression model were used to analyze the association between VAT and GDM/blood glucose. Results:A total of 3 686 pregnant women were included in this study, the mean age of participants was (30.56±4.05) years and 722 were diagnosed with GDM, with an incidence of 19.6%. The log-binomial regression model results showed that compared with VAT thickness Q1 (VAT<14.70 mm), the GDM risk in Q3 (21.65≤VAT≤29.69 mm) and Q4 (VAT ≥29.70 mm) increased by 34% [ RR(95% CI): 1.34 (1.08-1.67)], and 61% [ RR(95% CI): 1.61 (1.30-2.00)], respectively. Among women with gestational age<35 years old, compared with VAT thickness Q1, the risk of GDM increased by 42% in Q3 [ RR(95% CI): 1.42 (1.22-1.65)] and 70% [ RR(95% CI): 1.70 (1.46-1.98)] in Q4, whereas no associations were found in women with gestational age ≥35 years old ( P>0.05). The association between VAT and GDM risk was only found in pregnant women with pre-pregnancy BMI <24.0 kg/m 2, and the GDM risk increased by 57% [ RR(95% CI): 1.57 (1.22-2.04)] in Q3 and 65% [ RR(95% CI): 1.65 (1.24-2.19)] in Q4 compare with Q1. The results of multiple linear regression analysis showed that VAT was positively correlated with fasting blood glucose, 1-hour blood glucose after 75 g OGTT and 2-hours blood glucose after 75 g OGTT (all Pfor trend<0.001). Conclusion:High VAT thickness in early pregnancy is an independent risk factor for GDM, and the GDM risk increases with the raising of VAT depth.

Objective:To investigate the association between visceral adipose tissue (VAT) thickness in early pregnancy and the risk of gestational diabetes mellitus (GDM).Methods:Based on the Qingdao Women and Children Health Cohort, pregnant women in the first trimester (11-13 +6 weeks of gestation) were enrolled in this cohort study between May 2019 and October 2022. The VAT was measured in first trimester and determined as the distance from the inner margin of the rectus abdominis muscle to the anterior wall of the great artery using multi-functional color ultrasound. The 75 g oral glucose tolerance test (OGTT) results were followed up at 24-28 weeks and the participants were divided into GDM group and non-GDM group. The pregnant women were divided into 4 groups according to the VAT quartile. Log-binomial model and linear regression model were used to analyze the association between VAT and GDM/blood glucose. Results:A total of 3 686 pregnant women were included in this study, the mean age of participants was (30.56±4.05) years and 722 were diagnosed with GDM, with an incidence of 19.6%. The log-binomial regression model results showed that compared with VAT thickness Q1 (VAT<14.70 mm), the GDM risk in Q3 (21.65≤VAT≤29.69 mm) and Q4 (VAT ≥29.70 mm) increased by 34% [ RR(95% CI): 1.34 (1.08-1.67)], and 61% [ RR(95% CI): 1.61 (1.30-2.00)], respectively. Among women with gestational age<35 years old, compared with VAT thickness Q1, the risk of GDM increased by 42% in Q3 [ RR(95% CI): 1.42 (1.22-1.65)] and 70% [ RR(95% CI): 1.70 (1.46-1.98)] in Q4, whereas no associations were found in women with gestational age ≥35 years old ( P>0.05). The association between VAT and GDM risk was only found in pregnant women with pre-pregnancy BMI <24.0 kg/m 2, and the GDM risk increased by 57% [ RR(95% CI): 1.57 (1.22-2.04)] in Q3 and 65% [ RR(95% CI): 1.65 (1.24-2.19)] in Q4 compare with Q1. The results of multiple linear regression analysis showed that VAT was positively correlated with fasting blood glucose, 1-hour blood glucose after 75 g OGTT and 2-hours blood glucose after 75 g OGTT (all Pfor trend<0.001). Conclusion:High VAT thickness in early pregnancy is an independent risk factor for GDM, and the GDM risk increases with the raising of VAT depth.

Objective: We aimed to investigate whether 2-[ 18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[ 18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18;P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion Adding 2-[ 18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

OBJECTIVES: To compare the effect of different frequency of acupoint thread-embedding on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention. METHODS: A total of 126 subjects with overweight/obesity of spleen deficiency and dampness retention were randomized into a 2-week group(63 cases, 13 cases dropped out)and a 3-week group(63 cases, 11 cases dropped out, 1 case was eliminated). The two groups were treated with acupoint thread-embedding once every 2 weeks and once every 3 weeks respectively, Zhongwan(CV 12), Shuifen(CV 9), Qihai(CV 6), Guanyuan(CV 4) and bilateral Zhangmen(LR 13), Tianshu(ST 25), Liangmen(ST 21), Daheng(SP 15), Fujie(SP 14), Pishu(BL 20), Yinlingquan(SP 9)were selected. Four times were required in the two groups. Before and after treatment, follow-up after 2 months of treatment completion, the body mass index(BMI), body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, fat percentage(F%), skin fold thickness were observed in the two groups. RESULTS: After treatment and in follow-up, the BMI, body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, F%, skin fold thickness in the two groups were decreased compared with those before treatment (P<0.001, P<0.01), the changes of BMI, body weight, obesity degree, F%, skin fold thickness in the 2-week group were larger than those in the 3-week group(P<0.05, P<0.01, P<0.001). CONCLUSIONS The effect of acupoint thread-embedding once every 2 weeks on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention is superior to that once every 3 weeks.
Humans ; Acupuncture Points ; Overweight/therapy* ; Spleen ; Obesity/therapy* ; Body Weight ; Acupuncture Therapy ; Weight Loss

PURPOSE: Different arch structures may cause different foot function injuries. In the past, the arch structure and flexibility of the foot were often defined by the height of the arch, and there was no three-dimensional (3D) structure classification method. In order to form a more complete 3D description, we propose a new classification system of arch volume flexibility (AVF), and then use this new classification system to investigate the relationship between the AVF and arch index (AI), and the arch height flexibility (AHF) and AI, respectively. METHODS: It is proposed to recruit 180 young male adults for the test. We obtained arch volume and AI through 3D scanning and obtained the navicular height through manual measurement. Based on these data, we calculated the AHF and the AVF. Using the quintile method, these arches are divided into very stiff, stiff, neutral, flexible, and very flexible. According to AI value, all arches were divided into cavus, rectus, and planus. The distribution of AVF was compared using χ² goodness of fit test. The spearman correlation test was used to compare the AHF and AVF. A p < 0.05 indicates that the difference is statistically significant. RESULTS: All participants' plantar data was obtained through 3D scanning, but only 159 of them were complete, so only 318 feet had valid data. The left AHF is (21.23 ± 12.91) mm/kN, and the right AHF is (21.71 ± 12.69) mm/kN. The AVF of the left foot arch is (207.35 ± 118.28) mm³/kg, while the right one is (203.00 ± 117.92) mm³/kg, and the total AVF of the arch was (205.17 ± 117.94) mm³/kg. There was no statistical difference in the AVF between the left and right feet for the same participant (n = 159, p = 0.654). In cavus, the percentage of arch with AVF is 21.4% (very stiff), 21.4% (stiff), 14.3% (neutral), 7.1% (flexible), and 35.7% (very flexible). In rectus, the percentage of arch with AVF is 23.9% (very stiff), 19.6% (stiff), 14.7% (neutral), 24.5% (flexible), and 17.2% (very flexible). In planus, the percentage of arch with AVF is 14.9% (very stiff), 20.6% (stiff), 27.0% (neutral), 16.3% (flexible), and 21.3% (very flexible). Moreover, the correlation between AHF and AVF is not significant (p = 0.060). CONCLUSION In cavus, rectus, and planus, different AVF accounts different percentage, but the difference is not statistically significant. AVF is evenly distributed in the arches of the feet at different heights. We further found the relationship between AHF and AVF is not significant. As a 3D index, AVF may be able to describe the flexibility of the arch more comprehensively than AHF.
Adult ; Humans ; Male ; Foot ; Foot Injuries ; Biomechanical Phenomena

Our studies were aimed to explore the effect and mechanism of the inhibition of the formation of vasculogenic mimicry (VM) in human glioblastoma cells by Xihuang pill (XHP) medicated serum through regulating the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. The medicated serum of XHP was prepared by gavage for 7 days to male SD rats (approval number of animal experiment ethics: 202105A051). The hypoxia model of U251 cells was established using 200 μmol·L^-1 of CoCl₂. After treatment with XHP-medicated serum, cell viability and proliferation of U251 cells were detected by CCK-8 and cell cloning experiment. Cell apoptosis and cell cycle of U251 cells were determined by flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell invasion assay. The formation of VM was assessed by three-dimensional cell culture of U251 cells. The protein expression levels of HIF-1α, VEGFA, VEGFR2, phosphorylated-VEGFR2 (p-VEGFR2), vascular endothelial-cadherin (VE-cadherin), Eph receptor tyrosine kinases A2 (EphA2), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 14 (MMP14) and laminin γ2 in U251 cells were detected by Western blot. The results showed that 10% XHP-medicated serum had little effect on the cell viability, proliferation, apoptosis and cell cycle of U251 cells under hypoxia. Compared with the model group, 10% XHP-medicated serum at 1.0, 1.5 and 2.0 h significantly decreased the migration rate (P < 0.01) and the number of invading U251 cells (P < 0.01). 10% XHP-medicated serum at 2.0 h significantly suppressed the formation of VM tubular structures in U251 cells under the condition of hypoxia (P < 0.01). Western blot experiment showed that 10% XHP-medicated serum significantly down-regulated the expression of HIF-1α, VEGFA, phospho-VEGFR2, VE-cadherin, EphA2 and MMP14 proteins (P < 0.05). In conclusion, XHP could inhibit the formation of VM in human glioblastoma U251 cells to suppress the angiogenesis by down-regulating the HIF-1α/VEGFA/VEGFR2 signaling pathway.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*