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 investigate the effect of Mcart1 knockout on acute inflammation of macrophages in vitro and in vivo.Methods The Mcart1 knockout mice were used to establish a sepsis model induced by lipopolysaccharide(LPS),and the survival period was measured.Bone marrow derived macrophages(BMDM)of LPS-induced inflam-mation mice were cultured in DMEM high-glucose medium.The mRNA levels of M1 and M2 related cytokines of BM-DM after LPS stimulation were detected by RT-qPCR.The expression level of inflammation-related cytokines in serum of sepsis mice was detected by ELISA.Results Compared with wild type mice(Mcart1flox/flox),the survival time length of sepsis in Mcart1 knockout mice(Mcart1Lyz2-Cre)was significantly shortened(P＜0.001).After inflammation,the mRNA level of M1-related cytokines was up-regulated in BMDM cells of Mcart1Lyz2-Cre mice(P＜0.05);The mRNA level of M1-related cytokines was down-regulated(P＜0.05);The expression of M1-related mediators in serum of sep-sis Mcart1Lyz2-Cre mice was up-regulated(P＜0.01).Conclusions Mcart1 knockout can significantly raise the inflam-matory response of macrophages and aggravate the pathological symptoms of sepsis mice.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare autosomal dominant hereditary disorder characterized by hyperuricemia, gout, impaired urinary concentration, and progressive renal failure. It is primarily caused by mutations in uromodulin (UMOD) gene. This study reports a family with ADTKD in which whole-exome sequencing and Sanger sequencing identified a missense mutation in the UMOD gene, c.761A>C (p.H254P), present in both the proband and affected relatives. According to American College of Medical Genetics and Genomics (ACMG) guidelines, this variant is classified as likely pathogenic. The mutation results in an amino acid substitution that may impair UMOD protein folding and intracellular trafficking. UMOD gene mutations are associated with ADTKD, and genetic testing plays a vital role in the early diagnosis and treatment of this condition, highlighting its importance in the diagnosis of rare kidney diseases.
Adult ; Humans ; Male ; Exome Sequencing ; Mutation ; Mutation, Missense ; Nephritis, Interstitial/genetics* ; Pedigree ; Uromodulin/genetics*

Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases that share similar inflammatory mechanisms and characteristics. Programmed cell death (PCD) has recently garnered attention for its crucial role in regulating inflammation and maintaining tissue homeostasis, as well as for its potential to link these two diseases. The various forms of PCD--including apoptosis, pyroptosis, and necroptosis--are closely controlled by signaling pathways such as Toll-like receptor 4 (TLR4) /NF-κB and MAPK. These pathways determine cell fate and influence inflammatory responses, tissue destruction, and repair, and they both play important roles in the pathogenesis of RA and periodontitis. In periodontitis, periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis) and its virulence factors, including lipopolysaccharide (LPS), induce pyroptosis and necroptosis in immune cells such as macrophages via the TLR4/NF-κB pathway, which leads to an excessive release of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Concurrently, these pathogens inhibit the normal apoptotic process of immune cells, such as neutrophils, prolonging their survival, exacerbating immune imbalance, and aggravating periodontal tissue destruction. Similarly, in RA synovial tissue, fibroblast-like synoviocytes (FLS) acquire apoptosis resistance through signaling pathways such as the Bcl-2 family, JAK/STAT, and NF-κB, allowing for the consistent proliferation and secretion of matrix metalloproteinases and pro-inflammatory cytokines. Meanwhile, the continuous activation of pyroptotic pathways in neutrophils and macrophages results in the sustained release of IL-1β, further exacerbating synovial inflammation and bone destruction. Notably, dysregulated PCD fosters inter-organ crosstalk through shared inflammatory mediators and metabolic networks. Damage-associated molecular patterns (DAMPs) and cytokines that originate from periodontal lesions can spread systemically, influencing cell death processes in synovial and immune cells, thereby aggravating joint inflammation and bone erosion. By contrast, systemic inflammation in RA can upregulate osteoclastic activity or interfere with the normal apoptosis of periodontal cells via TNF-α and IL-6, ultimately intensifying periodontal immune imbalance. This review highlights the pivotal bridging role of PCD in the pathogenesis of both periodontitis and RA, providing a reference for therapeutic strategies that target cell death pathways to manage and potentially mitigate these diseases.

Objective:To explore the effects of ropivacaine ultrasound-guided serratus anterior plane block anesthesia on analgesia, oxygen metabolism and postoperative cognitive function in patients undergoing radical mastectomy.Methods:The study subjects were 110 patients with breast cancer treated in hospital from Sep. 2020 to Dec. 2023. They were divided into the control group ( n=55, general anesthesia) and the study group ( n=55, general anesthesia + ultrasound-guided serratus anterior plane block anesthesia) by random odd-even criteria. The analgesic effect, the level of oxygen metabolism index before and after operation, postoperative cognitive function and the occurrence of adverse reactions were compared. Results:The intraoperative dosage of sufentanil, remifentanil and propofol, and the number of analgesic pump compression within 48h in the study group were lower [ (241.82±19.82) μg, (581.42±52.77) mg, (107.22±9.81) μg, (3.47±1.02) times vs. (271.22±24.87) μg, (638.91±63.79) mg, (121.48±10.84) μg, (5.81±1.35) ], and the first time of postoperative analgesia pump was higher [ (7.59±1.44) h vs. (5.05±1.24) h], with statistically significant differences ( t=6.86, 5.15, 7.23, 10.26, 9.80; P<0.05). The visual analog scores in the study group were lower at 1h, 4h and 8h after surgery [ (1.11±0.25) points, (1.89±0.54) points, (1.65±0.45) points vs. (2.17±0.49) points, (2.68±0.64) points, (2.33±0.64) points], with statistically significant differences ( t=14.29, 7.00, 6.45, P<0.05). The difference of arterial-carotid vein oxygen content between the time of the beginning of operation and 1h after surgery in the study group was lower [ (37.22±2.22) ng/L, (34.89±1.86) ng/L vs. (42.77±2.05) ng/L, (42.77±2.05) ng/L], while carotid venous blood oxygen content and cerebral oxygen uptake rate were higher [ (94.32±2.78) ng/L, (97.39±2.64) ng/L, (37.26±2.31) %, (44.76±2.54) % vs. (81.82±1.35) ng/L, (89.53±2.04) ng/L, (42.86±2.06) %, (47.58±2.15) %], with statistically significant differences ( timmediately after the surgery =6.81, 8.12, 10.26, t1h after the surgery =12.54, 7.34, 10.54; P<0.05) ; The cognitive function scores in the study group at 1 and 7 days after surgery were higher [ (24.78±2.59) points, (26.35±1.84) points vs. (20.36±2.14) points, (24.66±1.57) points], with statistically significant differences ( t=9.76, 5.18, P<0.05). The incidence of adverse reactions was 5.46% in the study group and 18.18% in the control group, and the difference was statistically significant ( χ2 value=4.27, P<0.05) . Conclusion:Ropivacaine ultrasound-guided serratus anterior plane block anesthesia can improve the analgesic effect of breast cancer patients, ensure the balance of oxygen metabolism in brain tissue, and reduce the cognitive function damage of patients, and has excellent clinical application value.

Objective:To understand the real experience of caregivers of children with craniopharyngioma-associated hypothalamic obesity (CP-HO) based on the chronic disease trajectory model, so as to provide a reference for formulating corresponding disease management plans.Methods:From May 2023 to July 2023, semi-structured interviews were conducted with 17 caregivers of children with CP-HO who were admitted to the Department of Neurosurgery, Nanfang Hospital, Southern Medical University through purposive sampling. The interview data were analyzed by Colaizzi 7-step analysis method.Results:The 17 caregivers of children with CP-HO were 24 to 46 years old, including 3 males and 14 females. A total of 3 themes were extracted. Prodromal phase of weight: lack of disease cognition and weakening of self-concept; during the period of weight increase, the demand burden became prominent and the life pattern changed; weight stability: pressure, hope, and insight into the value of life.Conclusions:For promoting a good disease response of caregivers and improving the weight management effect of children and the quality of family life, medical staff should pay attention to and understand the disease care experience of children with CP-HO, and provide comprehensive and systematic solution strategies.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

OBJECTIVE To investigate the effect and possible mechanism of shikonin on neuroinflammation in sepsis- associated encephalopathy （SAE） rats by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS）-stimulator of interferon gene （STING） signaling pathway. METHODS Rats were randomly separated into SAE group， shikonin low-dose， medium-dose and high-dose groups （1.33， 2.66， 5.32 mg/kg）， high dose of shikonin+Roc A group （5.32 mg/kg shikonin+0.67 mg/kg cGAS-STING signaling pathway activator Roc A）， and control group， with 12 rats in each group. Except for the control group， SAE models were constructed in all other groups. After successful modeling， administration began once a day for 14 days. After administration， the Y-maze experiment and open-field experiment were applied to evaluate the learning and memory ability and anxiety state of rats， respectively. The pathological changes of neurons in the dentate gyrus （DG） of the hippocampus were observed. The number of CD86 and CD206 positive cells， the levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10， and the protein expressions of cGAS and STING were detected in the brain tissue of the hippocampus DG region. RESULTS Compared with the SAE group， the neuronal damage of rats in shikonin low-dose， medium-dose and high-dose groups were improved； the percentage of activity distance in the “new arm”， the duration of stay in the central area， walking distance， the number of intact neurons and CD206 positive cells in the brain tissue of the hippocampal DG area， and the levels of IL-4 and IL-10 increased/rised/prolonged significantly （P＜0.05）； the number of CD86 positive cells in the brain tissue of the hippocampal DG region， the levels of IL-1β and TNF-α， and protein expressions of cGAS and STING were significantly reduced/decreased/down-regulated （P＜0.05）， and the effect of shikonin was dose-dependent （P＜0.05）. Roc A could significantly reverse the improvement effect of high-dose shikonin on neuroinflammation in SAE rats （P＜0.05）. CONCLUSIONS Shikonin can improve neuroinflammation in SAE rats by inhibiting cGAS-STING signaling pathway.

In the process of promoting the implementation and transformation of the Q3D guideline of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) in China, the risk assessment of elemental impurities in naturally sourced excipients often faces challenges such as multiple types of elemental impurities and insufficient detection methods. In this paper, an inductively coupled plasma mass spectrometry (ICP-MS) method for screening 12 elemental impurities in titanium dioxide was established using the optimized acid extraction pre-treatment method. The accuracy and repeatability of the method were good. The recoveries of cadmium, lead, mercury, cobalt, nickel, lithium, barium, molybdenum, copper, chromium and iron were 83.6%−101.6%, the recovery of antimony was 54.1%, and the RSD was 1.1%−10.2% (n=6). The evaluation results of elemental impurities showed that the risk of cadmium, mercury, cobalt, nickel, lithium, barium, molybdenum, copper, chromium and antimony was low, while the risk of lead was high, and it is recommended that a lead salt test be added to the pharmacopoeia standard for this product. Based on the statistical data, the differences in the control levels of elemental impurities and whiteness of 29 batches of titanium dioxide samples from 10 domestic and foreign manufacturers were compared and analyzed. The Pearson correlation coefficient method was used to analyze the correlation between residual elemental impurities and whiteness, and a heat map was used to visualize the results. The results showed that whiteness was significantly negatively correlated with the amount of residual barium and the sum of residual elemental impurities. It is suggested that the manufactures should include whiteness as an internally controlled indicator to further improve the quality of titanium dioxide used as a pharmaceutical excipient.

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.