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.

Microorganisms, abundant in nature, are prolific producers of a diverse array of natural products (NPs) that are fundamental in the development of innovative therapeutics. Despite their significant potential, the field faces considerable challenges, including the continuous emergence of potential health threats, as well as novel pathogen strains and viruses. The advent and implementation of advanced technologies, such as culture strategies, genomics mining, and artificial intelligence (AI), are facilitating a paradigm shift in pharmaceutical research, introducing innovative methodologies and perspectives. The development and maturation of these technologies have enhanced the exploration of microbial-derived NPs, thereby advancing pharmaceutical research and development. This review synthesizes recent developments in this context, emphasizing their applications in pharmaceutical discovery and development. Through systematic analysis and synthesis, it provides objective insights into the promising prospects and future direction of this essential field.
Biological Products/chemistry* ; Drug Discovery ; Humans ; Artificial Intelligence ; Bacteria/metabolism*

BACKGROUND:Cervical spondylotic myelopathy is a progressive disease leading to dysfunction in the middle-aged and elderly,and early diagnosis is difficult.In recent years,some clinical scholars have found that dynamic magnetic resonance imaging technology can detect spinal cord compression in a dynamic position earlier,but its specific biomechanical mechanism needs to be clarified. OBJECTIVE:To investigate the biomechanical compression characteristics of early cervical spondylotic myelopathy in hyperextension and flexion position,and to verify the effectiveness of dynamic magnetic resonance imaging in the diagnosis of early cervical spondylotic myelopathy. METHODS:A retrospective analysis was made on the patients who underwent cervical dynamic magnetic resonance imaging in the Department of Orthopedics of First Affiliated Hospital of Guangxi University of Chinese Medicine from January to June 2022.16 subjects were selected and divided into two groups.The pathological group included 8 patients with early cervical spondylotic myelopathy with hypertrophy of ligamentum flavum as the main sign,with 5 male patients and 3 female patients.The normal group included 8 normal degenerative people,with 4 male patients and 4 female patients.All patients were photographed with cervical CT plain scan,magnetic resonance imaging plain scan,and dynamic magnetic resonance imaging plain scan.This study was divided into the following three parts:(1)collect the dynamic magnetic resonance imaging image DCOM data of two groups of subjects,and collect the cervical vertebra CT and neutral magnetic resonance imaging image DCOM data to understand the bone and soft tissue of the two groups of subjects in the neutral position.(2)Based on the DCOM data of magnetic resonance imaging and CT plain scan,the three-dimensional finite element models of lower cervical vertebra(C3-7)of normal degenerative population and early cervical spondylotic myelopathy patients were established by reverse engineering software.The equivalent stress and equivalent elastic strain of the spinal cord and posterior dura were analyzed,and the distribution of stress and strain was observed.(3)After obtaining the stress and strain data,the data between groups were compared to analyze the mechanical characteristics of spinal cord compression caused by early cervical spondylotic myelopathy in a dynamic position and to verify the effectiveness of dynamic magnetic resonance imaging in the diagnosis of early cervical spondylotic myelopathy. RESULTS AND CONCLUSION:(1)When simulating the posterior extension,flexion and neutral position of the lower cervical vertebrae(C3-7)in the two groups,the values of stress and strain in the posterior part of the spinal cord were in the following order:extension>flexion>neutral(P<0.05).The strain values from large to small were as follows:extension>flexion>neutral(P<0.05).(2)Compared with the normal degenerative population model,the equivalent stress and strain of the spinal cord in the pathological group were higher than those in the normal group under two degrees of freedom of flexion and extension(P<0.05).The distribution area of stress and strain in the posterior part of the spinal cord was irregular.(3)In the neutral position,there was no significant difference in the strain value of the spinal cord between the two groups(P>0.05),and the strain distribution was uniform and regular.(4)It is indicated that in the cervical extension position,the dural sac and the posterior part of the spinal cord were compressed and deformed in the early cervical spondylotic myelopathy patients with the hypertrophy of ligamentum flavum as the main sign,and the degree of compression deformation of the spinal cord was significantly higher than that in the anterior flexion position and neutral position.In the neutral position,there were no obvious signs of spinal cord deformation in patients with early cervical spondylotic myelopathy.This study verified the role of dynamic magnetic resonance imaging in the diagnosis of early cervical spondylotic myelopathy from the point of view of biomechanics.

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

Objective:To analyze the safety and effectiveness of superselective embolization of the uterine arteries in the treatment of uterine fibroids.Methods:The clinical data of 60 patients with uterine fibroids who were admitted to Zhejiang Veteran Hospital from February 2020 to February 2022 were retrospectively analyzed. These patients were divided into a control group and an observation group ( n = 30/group) according to different surgical methods. The control group underwent conventional surgery. The observation group underwent superselective embolization of the uterine arteries. Uterine size, uterine fibroid size, postoperative hormone level, and complications were compared between the two groups. Results:There was no significant difference in total response rate between the observation and control groups [93.33 (28/30) vs. 83.33 (25/30), χ2 = 1.46, P > 0.05]. After surgery, serum estradiol, luteinizing hormone, follicle-stimulating hormone, and progesterone levels in the observation group were (164.14 ± 19.97) ng/L, (2.43 ± 1.47) IU/L, (2.51 ± 1.14) IU/L, and (5.05 ± 0.43) μg/L, respectively, which were significantly lower than (190.23 ± 21.62) ng/L, (3.78 ± 1.63) IU/L, (3.94 ± 1.23) IU/L, (8.22 ± 1.35) μg/L in the control group ( t = 4.86, 3.37, 4.67, 12.25, all P < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group [3.33% (1/30) vs. 20.00% (6/30), χ2 = 4.04, P < 0.05). Conclusion:Compared with conventional surgery, superselective embolization of the uterine arteries is more effective on uterine fibroids, better keep postoperative hormone level stable, and reduce or avoid short- and long-term complications. Therefore, superselective embolization of the uterine arteries for the treatment of uterine fibroids deserves the clinical promotion.

OBJECTIVE: To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects. METHODS: Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice. RESULTS: Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis. CONCLUSION Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.
Humans ; Animals ; Mice ; MicroRNAs/metabolism* ; Cell Line, Tumor ; Cell Proliferation/physiology* ; Mice, Nude ; Cell Movement/physiology* ; Colorectal Neoplasms/pathology* ; Luciferases/metabolism* ; Gene Expression Regulation, Neoplastic ; PTEN Phosphohydrolase/metabolism* ; Chemokine CXCL12/metabolism*

ObjectiveTo determine the prevalence of avian influenza viruses in the external environment of poultry in Anqing City， Anhui Province， and provide scientific evidence for prevention and control of animal-derived influenza in humans. MethodsA total of 28 farmers’ markets/farms in 10 counties （cities， districts） of Anqing City， Anhui Province， were selected as surveillance sites by simple random sampling strategy. Poultry faeces and other related samples were collected for 6 consecutive weeks. Real-time fluorescence quantitative PCR was used to examine the nucleic acids of influenza A virus. Subtypes H5， H7， and H9 of avian influenza virus were further tested in the positive samples. ResultsA total of 426 specimens were collected， among which 113 tested positive with a positive rate of 26.53%. Among the positive specimens， 104 were determined to be subtype H9， accounting for 92.04%. It did not significantly differ in the positive rate between the main and non-main urban areas （χ²<0.01， P>0.05） or among the specimens collected in different weeks （χ²=7.57， P>0.05）. However， it significantly differed in the positive rate among the specimens collected in the third week and other weeks （χ²=6.89， P<0.05）. Furthermore， among the different sampling sites， farms had the highest positive rate of 46.67%. Among the specimens from different sources， the surface-coated specimens from poultry cages had the highest positive rate of 34.78%. ConclusionAvian influenza viruses are prevalent in the external environment of poultry in Anqing City. It warrants strengthening the surveillance and risk assessment to reduce the virus transmission in the external environment and risk of human infection with animal-derived influenza.

【Objective】 To explore the technical methods and clinical efficacy of transvaginal or transrectal repair in the treatment of iatrogenic bladder fistula. 【Methods】 The clinical data of 7 cases of iatrogenic bladder fistula patients treated during 2016 and 2019 were retrospectively analyzed, including 6 cases of vesicovaginal fistula (VVF) and 1 case of vesicorectal fistula (VRF). The operation was conducted 3 to 10 months after the diagnosis of urinary fistula, and the vagina or rectum was fully cleaned before operation. Modified Latzko technique was employed to separate the gap between the bladder wall and vaginal or rectal wall along the fistula, the fistula scar was sharply removed, and the fistula, bladder wall, vaginal or intestinal wall, and vaginal or intestinal mucosa were sutured in layers. The urinary catheter was indwelled for 4 weeks. 【Results】 All 7 cases were successfully repaired at one procedure. No urine leakage was found after the urinary catheter was removed. There was no recurrence after 6 to 12 months of follow-up. 【Conclusion】 Selective application of the modified Latzko technique to repair iatrogenic urinary fistula through the natural lumen is an advantageous treatment scheme, which simplifies the operation and reduces trauma.

【Objective】 To investigate the efficacy of the adjustable "paper clip" techniques in the suture of dorsal vein complex (DVC) and retention of urethral function in robot-assisted laparoscopic radical prostatectomy (RALRP). 【Methods】 A total of 30 cases of prostate cancer treated with RALRP were enrolled, all of which used the adjustable "paper clip" techniques. During operation, the DVC was sewed with barbed suture, and then a reverse suture was made through two sides of the prostatic ligaments. A Hem-o-lock was used to fasten the suture, which would be flexible to control the degree of tightness for the ligature. Perioperative and follow-up data of urinary continence and symptoms were collected and analyzed. 【Results】 All operations were successful. The estimated blood loss was (123.3±80.7) mL, 53.6% patients recovered continence in 1 month, and the continence rate increased to 92.9% and 96.3% at month 3 and 6. 92.9 of patients had no risk of incontinence 3 months after surgery. 【Conclusion】 The adjustable "paper clip" techniques have advantages in reducing blood loss, maintaining clear surgical field, preserving urethral function, and improving urinary continence.

Objective:To analyze the influential factors of hypothermia in congenital heart disease (CHD) after cardiopulmonary bypass (CPB) rewarming using the decision tree model, thus providing theoretical basis for medical staff.Methods:A total of 711 CHD children who underwent surgery in the Shanghai Children′s Medical Center from January 1, 2019 to April 30, 2019 were retrospectively analyzed.A decision tree model was established to predict the risk factors for hypothermia in CHD children following CPB.Results:The decision tree model showed that CPB program, preoperative nutrition score and body surface area were the high-risk factors for hypothermia in CHD children after CPB rewarming.The accuracy, sensitivity, specificity of the decision tree model were 86.45%, 77.14% and 90.97%, respectively, and the area under the receiver operating characteristic curve was 0.851(95% CI: 0.798-0.904). Conclusions:Decision tree model has a high application value in predicting hypothermia in CHD children following CPB.It contributes to identify the influential factors of hypothermia, and provides references for performing preventive treatment and nursing measures to control the risk of hypothermia.