The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

This paper explored the protective effect and potential mechanism of Shouhui Tongbian Capsules(SHTB) on cerebral ischemia-reperfusion rat models. Rats were randomly divided into sham surgery group, model group, low-dose SHTB group(0.2 g·kg~(-1)·d~(-1)), high-dose SHTB group(SHTB g·kg~(-1)·d~(-1)), and an edaravone positive drug group(5.4 mg·kg~(-1)·d~(-1)), with 12 rats in each group. Rats were given continuous intragastric administration seven days before surgery, and the suture method was used to establish the cerebral ischemia-reperfusion injury(CIRI) rat model. Zea-Longa rating scale for neurological functions was used to assess the degree of neurological function impairment in rats; hematoxylin-eosin(HE) staining was used to observe the pathological damage of rats' brain tissue; TTC staining was used to measure the area of cerebral infarction in rats; enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in each group. Western blot was used to detect the level of tight junction protein associated with the blood-brain barrier and intestinal barrier, as well as the protein expression of the TLR4/MyD88/NF-κB pathway in brain tissue. Changes in rats' brain tissue and metabolites in serum were detected by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), so as to explore the potential mechanism of SHTB treatment for CIRI in rats. Compared with the model group, SHTB could significantly alleviate the pathological damage to the brain of CIRI rats, reduce the volume of cerebral infarction, and lower the level of inflammation in the serum; Western blot results showed that SHTB could regulate the expression of tight junction proteins related to the blood-brain barrier and intestinal barrier in CIRI rats and downregulate the expression of TLR4, NF-κB, and MyD88 proteins in brain tissue. The UPLC-MS/MS results indicated that SHTB could significantly regulate the content of potential differential metabolites such as fatty acids, and serum and brain tissue are involved in pathways such as unsaturated fatty acid biosynthesis. SHTB could repair intestinal barrier function, reduce inflammation levels in the body, and improve the damaged blood-brain barrier, exerting a protective effect on brain nerves. Its mechanism may be achieved by balancing fatty acid metabolism and regulating the expression of TLR4/MyD88/NF-κB signaling pathway proteins.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Reperfusion Injury/genetics* ; Male ; Rats, Sprague-Dawley ; Brain Ischemia/genetics* ; Metabolomics ; Disease Models, Animal ; Myeloid Differentiation Factor 88/metabolism* ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Humans ; Brain/metabolism*

OBJECTIVE: To study the effect of ultrasound-guided fascia iliaca compartment block on perioperative analgesia and postoperative complications in geriatric patients with hip fractures. METHODS: A total of 127 elderly patients undergoing hip fracture surgery from January 2021 to September 2021 were randomized to receive ultrasound-guided continuous fascia iliaca compartment block(group F) either intravenous analgesia control group(group C). There were 62 cases in group F, including 19 males and 43 females with an average age of (82.4±7.2) years old ranging from 66 to 95 years old, involving 25 femoral neck fractures and 37 femoral intertrochanteric fractures. There were 65 cases in control group, including 18 males and 47 females, with an average age of (81.4±8.7) years old ranging from 65 to 94 years old, involving 29 femoral neck fractures and 36 femoral intertrochanteric fractures. The visual analogue scale(VAS), minimental state examination (MMSE), observer's assessment of alertness/sedation(OAA/S) scale, modified Bromage score, postoperative complications and general conditions during hospitalization in two groups were observed. RESULTS: The resting and exercise VAS at 30 min after block, anesthesia placement and 6, 24 and 48 h after surgery were lower than those in group C(P<0.05). In group F, MMSE scores at 12 h before surgery, and 1, 3 d after surgery and OAA/S scores at 3 d after surgery were higher than those in group C(P<0.05). The incidence of adverse effects and the number requiring additional analgesia were lower than those in group C(P<0.05). Group F had better perioperative analgesia satisfaction and hospital stay than group C(P<0.05). But there was no significant difference regarding Bromage score and 30-day mortality between two group(P>0.05). CONCLUSION Ultrasound-guided continuous fascia iliacus space block was safe and effective for elderly patients with hip fracture, and could significantly reduce perioperative pain, improve postoperative cognitive function, and reduce postoperative complications, thereby shortening hospital stay and improving the quality of life during hospitalization.
Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Pain Management ; Nerve Block ; Quality of Life ; Hip Fractures/surgery* ; Pain/surgery* ; Femoral Neck Fractures/surgery* ; Femoral Fractures/surgery* ; Ultrasonography, Interventional ; Postoperative Complications/surgery* ; Fascia ; Pain, Postoperative

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective: This study aims to survey the incidence of surgical site infection (SSI) in China and to analyze its risk factors, so as to prevent and control SSI after colorectal surgery. Methods: An observative study was conducted. Based on a program of Chinese SSI Surveillance from 2018 to 2020, the clinical data of all adult patients undergoing colorectal surgery during this time period were extracted. These included demographic characteristics and perioperative clinical parameters. Minors, pregnant women, obstetric or gynecological surgery, urological system surgery, retroperitoneal surgery, resection of superficial soft tissue masses, and mesh or other implants were excluded. A total of 2122 patients undergoing colorectal surgery from 50 hospitals were included, including 1252 males and 870 females. The median age was 63 (16) years and the median BMI was 23 (4.58) kg/m². The primary outcome was the incidence of SSI within 30 days after colorectal surgery. The secondary outcomes were mortality within 30 days postoperatively, length of ICU stays and postoperative hospital stays, and cost of hospitalization. Patients were divided into the SSI group and non-SSI group based on the occurrence of SSI. Multivariable logistic regression was performed to analyze risk factors of SSI after colorectal surgery, and subgroup analysis was conducted for open and laparoscopic surgery. Results: The incidence of SSI after colorectal surgery was 5.6% (119/2122), including 47 cases (47/119, 39.5%) with superficial incisional infections, 24 cases (24/119, 20.2%) with deep incisional infections, and 48 cases (48/119, 40.3%) with organ/space infections. The occurrence of SSI significantly increased mortality [2.5% (3/119) vs. 0.1%(3/2003), χ²=22.400, P=0.003], the length of ICU stay [0 (1) day vs. 0(0) day, U=131 339, P<0.001], postoperative hospital stay [18.5 (12.8) days vs. 9.0 (6.0) days, U=167 902, P<0.001], and medical expenses [75 000 (49 000) yuan vs. 60 000 (31 000) yuan, U=126 189, P<0.001] (P<0.05). Multivariate analysis revealed that hypertension (OR=1.782, 95%CI: 1.173-2.709, P=0.007), preoperative albumin level (OR=1.680, 95%CI: 1.089-2.592, P=0.019), a contaminated or infected incision (OR= 1.993, 95%CI: 1.076-3.689, P=0.028), emergency surgery (OR=2.067, 95%CI: 1.076-3.972, P=0.029), open surgery (OR=2.132, 95%CI: 1.396-3.255, P<0.001), and surgical duration (OR=1.804, 95%CI: 1.188-2.740, P=0.006) were risk factors for SSI, while preoperative skin preparation (OR=0.478, 95%CI: 0.310-0.737, P=0.001) was a protective factor for SSI. Subgroup analysis was performed on patients undergoing open or laparoscopic surgery. The incidence of SSI in the open surgery group was 10.2%, which was significantly higher than that in the laparoscopic or robotic group (3.5%, χ²=39.816, P<0.001). Subgroup analysis identified that a contaminated or infected incision (OR=2.168, 95%CI: 1.042-4.510, P=0.038) and surgical duration (OR=2.072, 95%CI: 1.171-3.664, P=0.012) were risk factors for SSI after open surgery, while mechanical bowel preparation (OR=0.428, 95%CI: 0.227-0.807, P=0.009) and preoperative skin preparation (OR=0.356, 95%CI: 0.199-0.634, P<0.001) were protective factors for SSI after open surgery. In laparoscopic surgery, diabetes mellitus (OR= 2.292, 95%CI: 1.138-4.617, P=0.020) and hypertension (OR=2.265, 95%CI: 1.234-4.159, P=0.008) were risk factors for SSI. Conclusions: The incidence of SSI after colorectal surgery is 5.6%. Minimally invasive surgery should be selected to reduce the occurrence of postoperative SSI. To prevent the occurrence of SSI after open surgery, skin preparation and mechanical bowel preparation should be performed before the operation, and the duration of the operation should be shortened as much as possible. In the perioperative period, care of patients with hypertension, diabetes, and contaminated or infected incisions should be given particular attention.
Adult ; Albumins ; China/epidemiology* ; Colorectal Surgery/adverse effects* ; Female ; Humans ; Hypertension/complications* ; Male ; Middle Aged ; Pregnancy ; Surgical Wound Infection/etiology*

Objectives: To evaluate the immunogenicity of Methods: Protein extracts from Results: Immunization with Conclusion This is the advanced study to investigate the immunogenicity of
Animals ; Antibodies, Bacterial/immunology* ; Antigens, Bacterial/immunology* ; Bacterial Proteins/immunology* ; Cross Reactions ; Cytokines/immunology* ; Female ; Genome, Bacterial ; Immunoglobulin G/immunology* ; Immunoglobulin M/immunology* ; Macrophages/immunology* ; Mice, Inbred BALB C ; Mycobacterium avium Complex/immunology* ; Mycobacterium tuberculosis/immunology* ; Tuberculosis Vaccines/administration & dosage* ; Whole Genome Sequencing

OBJECTIVE Compound Kushen injection (CKI) is a bis-herbal formulation extracted from Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Heterosmilacis Japonicae). Clinically, it is used as the adjuvant treat?ment of cancer. However, with the increased application, the cases of immediate hypersensitivity reactions (IHRs) also gradually rise. In this study, we investigated the underlying mechanism(s) and active constituent(s) for CKI-induced IHRs in experimental models. METHODS T helper 2 (Th2) immunity-amplified mice were prepared by aluminum adjuvant. Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice. For evaluating micro?vascular permeability, Evans blue extravasation assay was used. Platelet-activating factor (PAF), serum total IgE (tIgE) and mouse mast cell protease 1 (MMCP1) were measured by ELISA. RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks, but could induce Evans blue extravasation (local) and cause obvious hypothermia (systemic) after a single injection. Further study showed that alka?loids in Kushen, especially matrine, were responsible for CKI-induced IHRs. Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically. In cell system, CKI was able to promote PAF production in a non-cell-selective manner. In cell lysate, the effect of CKI on PAF production became stron?ger and could be abolished by blocking de novo pathway. CONCLUSION In conclusion, our study identifies, for the first time, that CKI is a PAF inducer. It causes non-immunologic IHRs, rather than IgE-dependent IHRs, by promoting PAF production through de novo pathway. Alkaloids in Kushen, especially matrine, are the prime culprits for IHRs. Our find?ings may provide a potential approach for preventing and treating CKI-induced IHRs.

Sepsis， a common critical disease in the intensive care unit（ICU）， features high morbidity and mortality. At present， it is mainly tackled with western medicine， which may trigger a series of problems like antibiotic resistance， adverse hormonal reactions， and high cost after a long-term use. Therefore， exploring new efficient， safe， and cheap drugs and treatment modes has become the focus of our research at this stage. By virtue of unique advantages including "the concept of holism and individualized treatment based on syndrome differentiation"， Chinese medicine has accumulated quite rich experience in the prevention and treatment of sepsis. In recent years， research on the regulation of Chinese medicine on nuclear transcription factor-κB（NF-κB） signaling pathway in sepsis has kept emerging. On this basis， this paper reviewed the etiology and pathogenesis of sepsis， syndrome differentiation and treatment， NF-κB signaling pathway， and its intervention with Chinese medicine. It has been found that some single Chinese herbs and their extracts， Chinese herbal compounds， and Chinese herbal injections effectively inhibit the expression of such inflammatory factors as NF-κB-mediated tumor necrosis factor-α（TNF-α）， interleukin-1（IL-1）， and IL-6 as well as the related proteins， reduce the systemic inflammatory response and organ injury， and improve the prognosis by regulating the activation of NF-κB signaling pathway and the immune function of macrophages. However， due to the limitations of objective conditions， some studies also have the problems of fuzzy pro-inflammatory anti-inflammatory balance mechanism， unclear pharmacokinetics and low drug safety evaluation， which need to be further studied and explored in order to provide a new theoretical basis and diagnosis and treatment thinking for the treatment of sepsis with traditional Chinese medicine.

Caffeic acid and its oligomers are the main water-soluble active constituents of the traditional Chinese medicine(TCM) Arnebiae Radix. These compounds possess multiple biological activities such as antimicrobial, antioxidant, cardiovascular protective, liver protective, anti-liver fibrosis, antiviral and anticancer activities. The phenylpropanoid pathway in plants is responsible for the biosynthesis of caffeic acid and its oligomers. Glycosylation can change phenylpropanoid solubility, stability and toxic potential, as well as influencing compartmentalization and biological activity. In view of the important role played by de-glycosylation in the regulation of phenylpropanoid homeostasis, the biosynthesis of caffeic acid and its oligomers are supposed to be under the control of relative UDP-glycosyltransferases(UGTs). Through the data mining of Arnebia euchroma transcriptome, we cloned 15 full-length putative UGT genes. After recombinant expression using the prokaryotic system, the crude enzyme solution of the putative UGTs was examined for the glycosylation activities towards caffeic acid and rosmarinic acid in vitro. AeUGT_01, AeUGT_02, AeUGT_03, AeUGT_04 and AeUGT_10 were able to glycosylate caffeic acid and/or rosmarinic acid resulting in different mono-and/or di-glycosylated products in the UPLC-MS analyses. The characterized UGTs were distantly related to each other and divided into different clades of the phylogenetic tree. Based on the observation that each characterized UGT exhibited substrate or catalytic similarity with the members in their own clade, we supposed the glycosylation abilities towards caffeic acid and/or rosmarinic acid were evolved independently in different clades. The identification of caffeic acid and rosmarinic acid UGTs from A. euchroma could lead to deeper understanding of the caffeic acid oligomers biosynthesis and its regulation. Furthermore, these UGTs might be used for regiospecific glycosylation of caffeic acid and rosmarinic acid to produce bioactive compounds for potential therapeutic applications.
Boraginaceae/genetics* ; Caffeic Acids ; Chromatography, Liquid ; Cinnamates ; Cloning, Molecular ; Depsides ; Glycosyltransferases/genetics* ; Phylogeny ; Tandem Mass Spectrometry

Nitrogen fertilizer has been the long-lasting crucial component in cultivation of Chinese materia medica(CMM) and crops for its profound effects on enhancing the productivity. In consideration of its role in better production, intensive and excessive application of N fertilizer is often found in CMM cultivation. Therefore, firstly, this review summarized various concentrations of N application with regards to different CMM and districts from the literatures published in the last two decades. The recommended concentration of nitrogen application of forty seven CMM species were covered in this review. We found that the optimum rates of nitrogen fertili-zer for different medicinal plants species were varied in the range between 0-1 035.55 kg·hm~(-2). Most of the optimum rates of nitrogen fertilizer for CMM in published researches fell between 100-199 kg·hm~(-2). The optimum rate of nitrogen fertilizer is not only related to amount of nitrogen required for different medicinal plants but also to soil fertilities of different fields. In addition, we outlined the diffe-rent effects of proper and excessive nitrogen deposition on yield of CMM. Proper nitrogen deposition benefits the yield of CMM, howe-ver, excessive nitrogen use accounts for a decrease in CMM yield. We elucidated that nutritional content, water use efficiencies, and photosynthesis capacity were major influencing factors. Researches showed that proper nitrogen fertilizer could promote the water use efficiencies of plants and boost photosynthesis. Consequently, the yield of CMM can be enhanced after nitrogen deposition. However, negative effects of nitrogen fertilizer were also found on plant including producing toxic substances to the soil and causing severe pest damages. Lastly we analyzed the impact of N fertilizer application on secondary metabolites which accounts for a large part of active pharmaceutical ingredients of CMM. It usually caused an increase in nitrogen-containing secondary metabolites content and a decrease in non-nitrogen-containing secondary metabolites content respectively. The potential underlying mechanisms are the different synthetic pathways of these metabolites and the plant nutritional status. Synthesis of non-nitrogen-containing secondary metabolites like phenols can be inhibited after nitrogen application because of the competition of the same precursor substances between metabolites synthesis and plant growth. To sum up, impacts and mechanisms of nitrogen fertilizer on yield and quality enhancement of CMM were discussed in this review. Negative effects of excessive nitrogen application on CMM should be paid special attention in CMM cultivation and prescription fertilization based on the field soil quality is strongly recommended. Overall, this review aims to provides insights on improving the proper application of N fertilizer in the cultivation of CMM.
Agriculture ; China ; Fertilizers ; Materia Medica ; Nitrogen/analysis* ; Soil