Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

Objective To explore the application value of simple drawing line puncture combined with visual articular process arthroplasty in lateral foraminoscopy.Methods A retrospective analysis was performed on 89 patients with single-segment lumbar disc herniation treated with lateral foraminoscopy from May 2019 to December 2022,including traditional transforaminal endoscopic spine system(TESSYS)technology(conventional group,35 cases)and simple drawing line puncture combined with visual articular process arthroplasty(modified group,54 cases).The fluoroscopy times,puncture time,and operation time of the two groups were compared.The Visual Analogue Score(VAS),Oswestry Disability Index(ODI),and MacNab criteria were used to evaluate the surgical effect at 3 d after surgery and at the last follow-up.Results All the operations were successfully completed without conversion to open surgery.In the conventional group,there was 1 case of L4 nerve root injury,who was considered intraoperative nerve root compression injury.There was no abnormality in lower limb muscle strength after surgery,but hyperalgesia and numbness in the innervated cutaneous area accompanied by nocturnal cramps.The patient was given treatment with pregabalin,mecobalamin,vitamin B1 and B6 for 2 months,and returned to normal at 1 year of follow-up.The other cases had no complications such as dural injury,abdominal organ injury,or incision infection.Recurrence occurred in 1 case in the conventional group and 2 cases in the modified group,and all the 3 cases occurred within 3 months after operation.Among them,2 patients had severe symptoms and underwent endoscopic revision again,and the other patient improved after conservative treatment.Compared with the conventional group,the puncture times[(1.8±0.7)times vs.(7.5±1.1)times,t=27.543,P=0.000].fluoroscopy times[(5.7±1.8)times vs.(23.2±2.2)times,t=41.235,P=0.000]and operation time[(72.7±7.2)min vs.(92.7±7.7)min,t=12.317,P=0.000]in the modified group were significantly reduced or shortened,and there was no significant difference in postoperative hospital stay[(3.2±0.6)d vs.(3.3±0.6)d,t=0.062,P=0.951]between the two groups.The conventional group was followed up for(14.0±1.3)months and the modified group was followed up for(13.6±1.2)months.There were no significant differences in VAS scores[(1.5±0.6)points vs.(1.6±0.7)points,t=0.751,P=0.455].ODI[(10.8±3.4)％vs.(11.8±3.9)％,t=1.284,P=0.202].and excellent and good rate of MacNab criteria[100％(54/54)vs.100％(35/35),Z=-0.981,P=0.327]between the two groups at the last follow-up.Conclusions Simple drawing line puncture combined with visual articular process arthroplasty can significantly improve the accuracy of intervertebral foramen aspiration,with simple operation,reduced X-ray exposure for doctors and patients,shortened operation time,and improved surgical safety.It is worthy of promotion and application in percutaneous foraminoscopy.

Objective To explore the application value of simple drawing line puncture combined with visual articular process arthroplasty in lateral foraminoscopy.Methods A retrospective analysis was performed on 89 patients with single-segment lumbar disc herniation treated with lateral foraminoscopy from May 2019 to December 2022,including traditional transforaminal endoscopic spine system(TESSYS)technology(conventional group,35 cases)and simple drawing line puncture combined with visual articular process arthroplasty(modified group,54 cases).The fluoroscopy times,puncture time,and operation time of the two groups were compared.The Visual Analogue Score(VAS),Oswestry Disability Index(ODI),and MacNab criteria were used to evaluate the surgical effect at 3 d after surgery and at the last follow-up.Results All the operations were successfully completed without conversion to open surgery.In the conventional group,there was 1 case of L4 nerve root injury,who was considered intraoperative nerve root compression injury.There was no abnormality in lower limb muscle strength after surgery,but hyperalgesia and numbness in the innervated cutaneous area accompanied by nocturnal cramps.The patient was given treatment with pregabalin,mecobalamin,vitamin B1 and B6 for 2 months,and returned to normal at 1 year of follow-up.The other cases had no complications such as dural injury,abdominal organ injury,or incision infection.Recurrence occurred in 1 case in the conventional group and 2 cases in the modified group,and all the 3 cases occurred within 3 months after operation.Among them,2 patients had severe symptoms and underwent endoscopic revision again,and the other patient improved after conservative treatment.Compared with the conventional group,the puncture times[(1.8±0.7)times vs.(7.5±1.1)times,t=27.543,P=0.000].fluoroscopy times[(5.7±1.8)times vs.(23.2±2.2)times,t=41.235,P=0.000]and operation time[(72.7±7.2)min vs.(92.7±7.7)min,t=12.317,P=0.000]in the modified group were significantly reduced or shortened,and there was no significant difference in postoperative hospital stay[(3.2±0.6)d vs.(3.3±0.6)d,t=0.062,P=0.951]between the two groups.The conventional group was followed up for(14.0±1.3)months and the modified group was followed up for(13.6±1.2)months.There were no significant differences in VAS scores[(1.5±0.6)points vs.(1.6±0.7)points,t=0.751,P=0.455].ODI[(10.8±3.4)％vs.(11.8±3.9)％,t=1.284,P=0.202].and excellent and good rate of MacNab criteria[100％(54/54)vs.100％(35/35),Z=-0.981,P=0.327]between the two groups at the last follow-up.Conclusions Simple drawing line puncture combined with visual articular process arthroplasty can significantly improve the accuracy of intervertebral foramen aspiration,with simple operation,reduced X-ray exposure for doctors and patients,shortened operation time,and improved surgical safety.It is worthy of promotion and application in percutaneous foraminoscopy.

Objective:To construct a recombinant bioluminescent bacteriophage (HT7) targeting Escherichia coli, and evaluate its ability to identify Escherichia coli. Methods:Initially, pCRISPR-sg (1-10) and PFN-1000 plasmid strains were constructed by genetic engineering, and the most efficient small guild RNA (sgRNA) were screened by bilayer plate. By the gene editing technique, which comprised homologous recombination and clustered regularly interspaced short palin dromic repeats (CRISPR)-Cas system, the Nanoluc luciferase gene was integrated into the downstream non-coding region of 10A gene of T7 phage, to constructe the bioluminescent phage HT7 successfully. The difference of biological characteristics between HT7 phage and T7 phage was evaluated by plaque assay and liquid amplification assay. In addition, 51 strains of Escherichia coli, 20 strains of Klebsiella pneumoniae, 14 strains of Staphylococcus aureus, 6 strains of Enterococcus faecium, 5 strains of Enterococcus faecalis, 3 strains of Acinetobacter baumannii and 1 strain of Pseudomonas aeruginosa were collected and isolated to evaluate the limit of detection and specificity of HT7 phage. Results:Among the 10 CRISPR-targeted cleavage systems constructed, sgRNA8 exhibited the highest cleavage efficiency, with a cleavage rate of 0.18. After three rounds of recombination screening using the pCas9/pCRISPR/PFN-1000 triple-plasmid system, PCR validation yielded recombinant phage bands at 2 798 bp, indicating the successful construction of the HT7 phage. The recombinant phage showed significant differences in biological characteristics in terms of lysis efficiency ( P<0.001), one-step growth curve ( P=0.001), and infection multiplicity ( P=0.031). Both lysis burst time and log growth node were extended by 10 min, with the optimal infection multiplicity being 0.1. Clinical sample testing identified lysis of 6 strains of Escherichia coli within 4.5 h, while other strains remained unaffected, with detection of pathogenic bacteria below 10 CFU/ml. Conclusions:The developed pCas9/pCRISPR/PFN-1000 triple-plasmid editing system efficiently edits the bacteriophage genome. The constructed HT7 fluorescent bacteriophage enables the detection of Escherichia coli below 10 CFU/ml within 4.5 hours, demonstrating low detection limits and high detection specificity.

ObjectiveTo observe the clinical efficacy of Tongdu Huoxue decoction in the treatment of acute lumbar disc herniation （LDH）. MethodA total of 316 patients with acute LDH admitted to the orthopedic outpatient department of Hubei Provincial Hospital of Traditional Chinese Medicine and Honghu City Hospital of Traditional Chinese Medicine from January 2020 to June 2023 were randomly divided into two groups. 156 cases in the control group （two cases with stopped follow-up） were treated with meloxicam tablets， while 153 cases in the observation group （five cases with stopped follow-up） were treated with Tongdu Huoxue decoction. Both groups were treated for three months. The clinical efficacy， McGill Pain Score Scale （SF-MPQ）， Oswestry Dysfunction Index （ODI） score， and the Japanese Orthopaedic Association （JOA） scores of the two groups before and after treatment were compared. The serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） of the patients before and after treatment were determined by using enzyme-linked immunosorbent assay （ELISA）. The NDI-092 type electromyography-evoked potential instrument was adopted to measure the motor conduction velocity and clinical efficacy of the tibial and common peroneal nerves in patients of the two groups before and after treatment， and the clinical safety of the two groups of patients was compared. ResultAfter treatment， the total effective rate in the observation group was 95.4% （146/153）， significantly higher than that in the control group of 76.3% （119/156） （χ² =23.18， P<0.05）. After treatment， both groups showed significant reductions in SF-MPQ and ODI scores， as well as the levels of IL-1β， IL-6， and TNF-α （P<0.05）， with the observation group showing a more significant reduction （P<0.05）. Both groups showed a significant increase in JOA scores and motor conduction velocities of the tibial and common peroneal nerves after treatment （P<0.05）， with the observation group showing a more significant increase （P<0.05）. ConclusionTongdu Huoxue decoction can alleviate lumbar and leg pain in acute LDH， improve lumbar spine function， and suppress inflammatory reactions. It is highly safe and is worthy of clinical promotion.

Objective To elucidate the role of programmed cell death factor 4(PDCD4)in mitochondrial dysfunction caused by sepsis-related vascular endothelial damage.Methods Cultured human umbilical vein endothelial cells(HUVECs)and mouse vascular endothelial cells(C166 cells)were transfected with a small interfering RNA targeting PDCD4 followed by treatment with lipopolysaccharide(LPS)alone or in combination with carbonyl cyanide 3-chlorophenylhydrazone(FCCP).The proteomic changes in the cells after PDCD4 knockdown were analyzed using LC-MS/MS technique.The mRNA expressions of PDCD4 and the genes associated with cell inflammation and apoptosis were detected with RT-PCR,and the expressions of FIS1,DRP1 and OPA1 proteins key to mitochondrial fission and fusion were determined using Western blotting.JC-1 and MitoSOX fluorescent probes were used to observe the changes in mitochondrial membrane potential and mitochondrial reactive oxygen species levels under by a laser confocal microscope.Results LPS stimulation of the cells significantly increased the mRNA expressions of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP1)and enhanced the cellular expression of PDCD4(P<0.05).Proteomic analysis suggested a correlation between PDCD4 knockdown and changes in mitochondrial dynamics in the cells.LPS treatment significantly increased the expressions of mitochondrial fission proteins FIS1 and DRP1 and lowered the expression of the fusion protein OPA1 in the cells(P<0.05),causing also mitochondrial oxidative stress and reduction of the mitochondrial membrane potential(P<0.05).In HUVECs,treatment with FCCP significantly attenuated the protective effect of PDCD4 knockdown,which inhibited LPS-induced inflammation and oxidative stress and restored the balance between mitochondrial fission and fusion.Conclusion PDCD4 knockdown protects vascular endothelial cells against LPS-induced damages by repressing mitochondrial fission and oxidative stress,promoting mitochondrial fusion,and maintaining normal mitochondrial function.

ObjectiveTo explore the possible mechanism of Osteoking （OK） on postmenopausal osteoporosis （PMOP）. MethodForty adult female mice were randomly divided into a sham operation （Sham） group， osteoporosis model （OVX） group， estradiol intervention （E₂） group， and OK group， with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy， and the corresponding drugs were given one week later. After 12 weeks， the body mass and uterine index of mice were measured， and the pathological changes of bone tissue and the number of osteoclasts （OCs） were determined by hematoxylin-eosin （HE） and tartrate-resistant acid phosphatase （TRAP） staining， respectively. Bone mineral density （BMD）， trabecular number （Tb.N）， trabecular separation （Tb.Sp）， and bone volume fraction （BV/TV） were measured by microcomputed tomography （Micro-CT）. The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α （TNF-α） and bone resorption marker C-terminal telopeptide of type Ⅰ collagen （CTX-1） were measured by enzyme linked immunosorbent assay （ELISA）. The protein expression levels of nuclear factor-kappa B p65 （NF-κB p65）， phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65）， nuclear factor kappa B inhibitor alpha （IκBα）， phosphorylated nuclear factor kappa B alpha （p-IκBα）， nuclear factor of activated T cells 1 （NFATc1）， and proto-oncogene （c-Fos） were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 （MMP-9）， NFATc1， TRAP， cathepsin K （CTSK）， and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the Sham group， the uterine index decreased significantly in the OVX group， and the body mass （BMI） increased significantly. The structure of bone trabeculae was completely damaged， and the number of OCs increased. BMD， Tb.N， BV/TV， and maximum load decreased， while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were up-regulated （P<0.05， P<0.01）. Compared with the OVX group， the body mass of the OK and E₂ groups decreased， and the uterine index increased. The bone trabeculae increased， and the number of OCs decreased. BMD， Tb.N， BV/TV， and maximum load increased， while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were decreased， and the mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were decreased （P<0.05， P<0.01）. ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice， which is one of the mechanisms for treating PMOP.

In the context of the new era of metaverse, this article summarizes and analyzes the rapid development of medical education in the new situation and the current research status of new teaching model for medical imaging. Moreover, this article focuses on how to build a metaverse medical imaging teaching resource library, construct a virtual environment for metaverse medical imaging teaching, and create a learning platform for metaverse medical imaging teaching. The article also describes the logic and plan of a course for practicing the new teaching model for medical imaging in the context of metaverse. Virtual teaching was carried out for the specific theme course "Head MRI", and the teaching experience for medical imaging in the context of metaverse was explored and summarized, which provides a reference for achieving diversified teaching.

Objective To elucidate the role of programmed cell death factor 4(PDCD4)in mitochondrial dysfunction caused by sepsis-related vascular endothelial damage.Methods Cultured human umbilical vein endothelial cells(HUVECs)and mouse vascular endothelial cells(C166 cells)were transfected with a small interfering RNA targeting PDCD4 followed by treatment with lipopolysaccharide(LPS)alone or in combination with carbonyl cyanide 3-chlorophenylhydrazone(FCCP).The proteomic changes in the cells after PDCD4 knockdown were analyzed using LC-MS/MS technique.The mRNA expressions of PDCD4 and the genes associated with cell inflammation and apoptosis were detected with RT-PCR,and the expressions of FIS1,DRP1 and OPA1 proteins key to mitochondrial fission and fusion were determined using Western blotting.JC-1 and MitoSOX fluorescent probes were used to observe the changes in mitochondrial membrane potential and mitochondrial reactive oxygen species levels under by a laser confocal microscope.Results LPS stimulation of the cells significantly increased the mRNA expressions of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP1)and enhanced the cellular expression of PDCD4(P<0.05).Proteomic analysis suggested a correlation between PDCD4 knockdown and changes in mitochondrial dynamics in the cells.LPS treatment significantly increased the expressions of mitochondrial fission proteins FIS1 and DRP1 and lowered the expression of the fusion protein OPA1 in the cells(P<0.05),causing also mitochondrial oxidative stress and reduction of the mitochondrial membrane potential(P<0.05).In HUVECs,treatment with FCCP significantly attenuated the protective effect of PDCD4 knockdown,which inhibited LPS-induced inflammation and oxidative stress and restored the balance between mitochondrial fission and fusion.Conclusion PDCD4 knockdown protects vascular endothelial cells against LPS-induced damages by repressing mitochondrial fission and oxidative stress,promoting mitochondrial fusion,and maintaining normal mitochondrial function.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.