ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

This paper reviews the published articles of recent years on the application of deep learning methods in automatic localization of acupoint, and summarizes it from 3 key links, i.e. the dataset construction, the neural network model design, and the accuracy evaluation of acupoint localization. The significant progress has been obtained in the field of deep learning for acupoint localization, but the scale of acupoint detection needs to be expanded and the precision, the generalization ability, and the real-time performance of the model be advanced. The future research should focus on the support of standardized datasets, and the integration of 3D modeling and multimodal data fusion, so as to increase the accuracy and strengthen the personalization of acupoint localization.
Deep Learning ; Acupuncture Points ; Humans ; Neural Networks, Computer

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

The construction of experimental animal models plays an important supporting role in research into the mechanisms of action of Chinese medicines.There have been increasing reports of the construction and evaluation of animal models of spleen deficiency;however,the construction method have involved different standards and there has been insufficient objectification of the evaluation indexes.In this review,we summarize the construction and evaluation method of animal models of spleen deficiency from the aspects of animal selection,model establishment,macroscopic characterization,behavioral experiments,and objective indexes of spleen deficiency,with a view to providing theoretical guidance for the construction of experimental animal models of spleen deficiency and references for the selection of animal model platforms for spleen deficiency.

Objective This study aimed to develop an experimental animal platform for evaluating the feasibility and safety of intelligent acupuncture robots and to lay the foundation for further research.Methods Six 2-month-old Guangxi Bama miniature pigs were used as experimental subjects for acupuncture verification after anesthesia.First,manual acupuncture verification was carried out.Six acupoints were selected for each experimental animal and the needles were left for 20 min after the lifting,inserting,and twisting manipulation.Before and after controls were included.The experiment was carried out for 28 days,and each experiment was conducted once every 2 days for a total of 10 times.After verification of manual acupuncture,a point 10 mm from each of the six selected acupoints was selected,with a total of 12 points,and acupuncture operations were carried out on the experimental animals using the intelligent acupuncture module of the acupuncture robot at different frequencies and angles,to further verify the stability and feasibility of the animal platform.Results Routine safety-related blood indicators and blood biochemistry indicators after the procedure were normal and stable compared with those before the procedure.The average heart rate of the animals was 124 beats/min,the average blood pressure was 87/36 mmHg,and the average body temperature of was 36℃at a room temperature of 25℃,with no significant change in body temperature during and after the experiment.On the basis of this experimental platform,acupuncture manipulation using the intelligent acupuncture module of the acupuncture robot was completed successfully,with no abnormalities related to acupuncture such as bending,breaking,or stagnation of needles during the experimental process,and the experimental animals showed no obvious abnormalities.Conclusions This study established a stable experimental animal platform for evaluating the feasibility and safety of acupuncture carried out by intelligent acupuncture robots,based on the existing experimental method of miniature pigs.These result lay a foundation for further research related to the use of intelligent acupuncture robots.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy. This paper provides a review of the pathways involved in the development of ACC and the progress of targeted drug therapy. The pathways reviewed include Wnt/β-catenin, P53, epithelial-mesenchymal transition(EMT), insulin growth factor(IGF) and fibroblast growth factor(FGF) signalling pathways.

Objective:To explore the safety and feasibility of adrenal tumor resection under day surgery mode for the treatment of unilateral primary aldosteronism (UPA).Methods:The clinical data of 83 patients who underwent adrenalectomy for the treatment of UPA from January 2020 to January 2023 were retrospectively analyzed. There were 42 males (50.6%)and 41 females (49.4%), age (49.0±12.3)years old. Body mass index (25.4±3.6)kg/m 2. There were 17 patients with diabetes, 58 patients with preoperative hypertension, and the duration of hypertension was 8.2(1, 15)years. Systolic blood pressure was 151.8(137.0, 160.0)mmHg (1 mmHg=0.133 kPa), and diastolic blood pressure was 97.4(87.0, 107.0)mmHg. 20 cases had severe preoperative hypokalemia, with preoperative blood potassium levels of (2.9±0.6)mmol/L. The ratio of preoperative plasma aldosterone to renin activity was 54.1(13.0, 77.2). Tumors were located on the left side in 47 cases (56.6%)and on the right side in 36 cases (43.4%). The maximum diameter of the tumor is 1.5(1.0, 1.7)cm. Patients diagnosed with unilateral primary aldosteronism were included, and patients diagnosed with adrenal pheochromocytoma, adrenal malignancy, or severe cardiovascular disease that cannot tolerate surgery were excluded. The patient was admitted to the hospital on the same day, underwent surgery on the same day, and was evaluated after extubation within one day after surgery. The patient had no fever or lower back pain after surgery, was able to freely get out of bed, and had no obvious abnormalities in blood routine, electrolyte and other test indicators. The patient was discharged from the hospital and received continuous care outside the hospital. The patient was guided to undergo regular outpatient follow-up. Evaluate the efficacy using the Primary Aldosterone Hyperaldosteronism Surgical Outcome (PASO)criteria. Results:The patients had a mean length of hospital stay of 43.0(40.3, 44.6)hours, an operation time of 89.6(70.0, 103.0)minutes, and an operation cost of 23 820.2 (21 150.8, 24 948. 3)yuan. The postoperative free position time was 29.5(20.8, 39.7)hours, the postoperative time for fluid placement of the diet was 25.2(20.1, 27.8) hours, and 42.2(37.9, 41.9)hours of postoperative drain removal. The overall postoperative clinical remission rate was 85.5%. There were four postoperative complications, accounting for 4.8% of cases. These included two cases of interosseous vein thrombosis, one case of delayed healing, and one case of peritoneal rupture. No case of readmission was reported within 30 days.Conclusions:UPA adrenal tumour resection in ambulatory mode is safe and effective when strict inclusion and exclusion criteria are followed, adequate preoperative preparation is carried out, and expert physician assessment is provided.

Objective:To evaluate the predictive value of preoperative frailty combined with nutritional status for prolonged postoperative ileus (PPOI) in the patients with gynecological malignancies.Methods:Patients undergoing elective surgery for gynecological malignancies in the Affiliated Hospital of Jiangnan University from April 2022 to February 2023 were selected. The Frail scale was used to evaluate the frailty within 24 h of admission, and the nutritional status was evaluated by the Controlling Nutritional Status score. The general characteristics of patients and occurrence of PPOI were recorded, and the risk factors for PPOI were analyzed by multivariate logistic regression. The ability of frailty, nutritional status and their combination to predict PPOI was assessed by the receiver operating characteristic curve.Results:Two hundred and fourteen patients were finally included, 52 cases developed of PPOI, and 98 cases were frail patients. Preoperative frailty combined with moderate to severe malnutrition was an independent risk factor for PPOI in the patients with gynecological malignancies ( P<0.05), and the area under the curve in predicting the occurrence of PPOI was 0.796 (95% confidence interval 0.736-0.857) in the patients with gynecological malignancies. Conclusions:Preoperative frailty combined with moderate to severe malnutrition has a higher accuracy in predicting PPOI in the patients with gynecological malignancies.

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.