ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

BACKGROUND:Distinct risk factors for new adjacent vertebral fractures following percutaneous vertebroplasty in the elderly patients with osteoporotic vertebral compression fractures and underlying diseases may be different,yet there is a scarcity of pertinent research on this topic.OBJECTIVE:To investigate the high-risk factors for refracture in patients with osteoporotic vertebral compression fractures following percutaneous vertebroplasty and to delve deeper into the correlation between these risk factors and the recurrence of fractures in the operated vertebra as well as its adjacent vertebrae post-percutaneous vertebroplasty.METHODS:According to the inclusion criteria,412 patients with osteoporotic vertebral compression fractures who underwent percutaneous vertebroplasty at the Sixth Affiliated Hospital of Xinjiang Medical University between January 2018 and December 2023 were retrospectively screened.According to whether re-fracture occurred during the follow-up period,the patients were divided into a re-fracture group(n=75)and a non-re-fracture group(n=337).The following variables of the two groups of patients were reviewed:age,gender,body mass index,cement leakage,bone density T value,cement dosage,occupation,smoking,drinking,adverse reactions,medical insurance,hypertension,type 2 diabetes,chronic obstructive pulmonary disease,cerebral hemorrhage,coronary heart disease,psychological trauma,psychiatric treatment,osteoarthritis,gout,scoliosis,spinal surgery,chronic kidney,anti-osteoporosis treatment,previous fracture history(fracture caused by osteoporosis)and fracture injury plane.The above factors were analyzed using univariate analysis.The factors with P＜0.05 were subjected to binary logistic analysis to explore the related factors of postoperative vertebral recompression fracture.RESULTS AND CONCLUSION:(1)Univariate analysis showed that after percutaneous vertebroplasty,vertebral refracture was associated with age,smoking history of＞10 years,cement leakage,hypertension,type 2 diabetes,scoliosis,spinal surgery,and chronic kidney disease,with statistically significant differences(P＜0.05).(2)By binary Logistic regression,bone cement leakage condition(OR=2.547,95％CI:1.283-5.048,P＜0.05),smoking history＞10 years(OR=2.336,95％CI:1.157-4.701,P＜0.05),a history of hypertension(OR=4.657,95％CI:2.137-10.242,P＜0.05),a history of type 2 diabetes mellitus(OR=8.956,95％CI:3.941-21.301,P＜0.05),and a medical history of scoliosis(OR=3.754,95％CI:1.755-8.619,P＜0.05),medical history of spinal surgery(OR=2.700,95％CI:1.058-6.725,P＜0.05),and a history of chronic kidney disease(OR=2.812,95％CI:1.078-7.739,P＜0.05)were risk factors for refracture of the operated vertebral body and adjacent vertebrae.(3)The results showed that cement leakage,smoking for＞10 years,hypertension,type 2 diabetes mellitus,scoliosis,spinal surgery,and chronic kidney were risk factors for recurrent fractures of the operated vertebrae and adjacent vertebrae in patients with osteoporotic vertebral compression fractures.Surgeons should conduct a comprehensive assessment of patients before percutaneous vertebroplasty in order to more accurately predict the possibility of re-fracture and provide a basis for the formulation of personalized treatment plans to reduce the risk of future recurrent fractures.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BACKGROUND:Distinct risk factors for new adjacent vertebral fractures following percutaneous vertebroplasty in the elderly patients with osteoporotic vertebral compression fractures and underlying diseases may be different,yet there is a scarcity of pertinent research on this topic.OBJECTIVE:To investigate the high-risk factors for refracture in patients with osteoporotic vertebral compression fractures following percutaneous vertebroplasty and to delve deeper into the correlation between these risk factors and the recurrence of fractures in the operated vertebra as well as its adjacent vertebrae post-percutaneous vertebroplasty.METHODS:According to the inclusion criteria,412 patients with osteoporotic vertebral compression fractures who underwent percutaneous vertebroplasty at the Sixth Affiliated Hospital of Xinjiang Medical University between January 2018 and December 2023 were retrospectively screened.According to whether re-fracture occurred during the follow-up period,the patients were divided into a re-fracture group(n=75)and a non-re-fracture group(n=337).The following variables of the two groups of patients were reviewed:age,gender,body mass index,cement leakage,bone density T value,cement dosage,occupation,smoking,drinking,adverse reactions,medical insurance,hypertension,type 2 diabetes,chronic obstructive pulmonary disease,cerebral hemorrhage,coronary heart disease,psychological trauma,psychiatric treatment,osteoarthritis,gout,scoliosis,spinal surgery,chronic kidney,anti-osteoporosis treatment,previous fracture history(fracture caused by osteoporosis)and fracture injury plane.The above factors were analyzed using univariate analysis.The factors with P＜0.05 were subjected to binary logistic analysis to explore the related factors of postoperative vertebral recompression fracture.RESULTS AND CONCLUSION:(1)Univariate analysis showed that after percutaneous vertebroplasty,vertebral refracture was associated with age,smoking history of＞10 years,cement leakage,hypertension,type 2 diabetes,scoliosis,spinal surgery,and chronic kidney disease,with statistically significant differences(P＜0.05).(2)By binary Logistic regression,bone cement leakage condition(OR=2.547,95％CI:1.283-5.048,P＜0.05),smoking history＞10 years(OR=2.336,95％CI:1.157-4.701,P＜0.05),a history of hypertension(OR=4.657,95％CI:2.137-10.242,P＜0.05),a history of type 2 diabetes mellitus(OR=8.956,95％CI:3.941-21.301,P＜0.05),and a medical history of scoliosis(OR=3.754,95％CI:1.755-8.619,P＜0.05),medical history of spinal surgery(OR=2.700,95％CI:1.058-6.725,P＜0.05),and a history of chronic kidney disease(OR=2.812,95％CI:1.078-7.739,P＜0.05)were risk factors for refracture of the operated vertebral body and adjacent vertebrae.(3)The results showed that cement leakage,smoking for＞10 years,hypertension,type 2 diabetes mellitus,scoliosis,spinal surgery,and chronic kidney were risk factors for recurrent fractures of the operated vertebrae and adjacent vertebrae in patients with osteoporotic vertebral compression fractures.Surgeons should conduct a comprehensive assessment of patients before percutaneous vertebroplasty in order to more accurately predict the possibility of re-fracture and provide a basis for the formulation of personalized treatment plans to reduce the risk of future recurrent fractures.

This study systematically examined the effects of atomization as a transdermal permeation enhancer on the transdermal delivery of active ingredients with different physicochemical properties and investigated the underlying mechanisms. Porcine ear skin served as an in vitro model, and skin permeation experiments were conducted using Franz diffusion cells. Receptor fluids were collected at specific time points, and samples of the stratum corneum and viable epidermis–dermis were separated and prepared. Quantitative and visualization methods, including high-performance liquid chromatography, fluorescence derivatization, and confocal laser scanning microscopy, were used to compare skin retention and transdermal permeation of adenosine (AD), tranexamic acid (TXA), calcein (CAL), and tocopheryl acetate (TA) under atomized and non-atomized conditions. Additionally, transepidermal water loss (TEWL) measurements and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) were employed to analyze the mechanism behind the penetration enhancement caused by atomization. The findings showed that atomization increased skin retention within the stratum corneum and viable epidermis–dermis, as well as the transdermal permeation of all four active ingredients to varying degrees. The most significant enhancement was observed for TXA, which has a relatively low molecular weight and moderate lipophilicity, while the enhancement effects for highly hydrophilic AD and highly lipophilic TA were comparatively limited; however, atomization significantly increased the skin retention of TA. TEWL results indicated that skin permeability increased within 4 hours after atomization and largely recovered within 8 hours. ATR-FTIR analysis suggested that atomization may facilitate transdermal delivery by disrupting the lipid order and keratin conformation in the stratum corneum.This study provides theoretical support and experimental references for the advancement of atomization transdermal delivery technology, as well as the design and development of related atomization products.

Exercise-induced muscle damage (EIMD) is a frequent form of skeletal muscle microdamage that occurs after high-intensity, prolonged, or unaccustomed exercise, especially exercise dominated by eccentric contractions. It is commonly characterized by delayed-onset muscle soreness, transient loss of muscle strength, local inflammation, structural disruption of myofibers, and delayed functional recovery. Although mild EIMD may serve as a stimulus for training adaptation, excessive or insufficiently recovered muscle damage can impair exercise performance, disturb training continuity, and reduce participation in physical activity. Therefore, clarifying the molecular mechanisms that underlie the initiation, amplification, and resolution of EIMD is important for optimizing athletic training, improving post-exercise recovery, and guiding evidence-based public fitness practice. Necroptosis is a regulated form of programmed cell death mediated primarily by the receptor-interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling axis. Recent studies have shown that necroptosis is closely involved in tissue injury, sterile inflammation, and repair remodeling. However, whether necroptosis acts as an initiating driver, a secondary damage amplifier, or an adaptive signal required for repair after EIMD remains unclear. This review aimed to summarize the potential role of necroptosis in EIMD and to establish a mechanistic framework linking regulated cell death, inflammatory amplification, immune regulation, and skeletal muscle repair. Relevant studies concerning EIMD, necroptosis, RIPK1/RIPK3/MLKL signaling, damage-associated molecular patterns (DAMPs), inflammatory responses, immune cell recruitment, extracellular matrix remodeling, and muscle regeneration were reviewed and integrated. On this basis, the possible temporal and functional involvement of necroptosis in different phases of EIMD was analyzed. The main evidence summarized in this review suggests that EIMD is not merely a consequence of primary mechanical disruption. Instead, it develops through a dynamic sequence that includes sarcolemmal instability, calcium overload, mitochondrial dysfunction, oxidative stress, inflammatory mediator production, immune cell infiltration, necrotic tissue clearance, and regeneration-associated remodeling. Necroptosis may participate in this process through at least two interconnected mechanisms. First, in the early or progressive phase of EIMD, activation of the RIPK1/RIPK3/MLKL signaling axis may promote MLKL phosphorylation and plasma membrane permeabilization, leading to the release of DAMPs such as high-mobility group box 1, ATP, mitochondrial DNA, and other intracellular components. These signals may activate innate immune pathways, amplify inflammatory cytokine production, and enhance the recruitment of neutrophils and macrophages, thereby aggravating secondary inflammation and extending muscle fiber injury. Second, during the resolution and repair phases, necroptosis-related signaling may also contribute indirectly to the formation of a regenerative microenvironment. By influencing the clearance of necrotic debris, the recruitment and phenotypic transition of immune cells, and the remodeling of extracellular matrix components, necroptosis may affect satellite cell activation, myogenic repair, and the eventual structural and functional recovery of injured skeletal muscle. Thus, the biological effect of necroptosis in EIMD may be context dependent rather than uniformly harmful. Its outcome may depend on exercise intensity, the extent of tissue damage, the timing of pathway activation, the involved cell types, inflammatory status, training background, age, and metabolic condition. In conclusion, necroptosis may represent an important molecular link between skeletal muscle injury, sterile inflammation, and tissue repair after damaging exercise. It may exert a dual role in EIMD by amplifying secondary damage while also contributing to repair coordination under appropriate temporal and microenvironmental conditions. Future studies should determine the activation pattern of RIPK1/RIPK3/MLKL signaling after different exercise protocols, identify the major cell populations undergoing necroptosis in injured skeletal muscle, and examine whether targeted modulation of necroptosis can reduce excessive inflammation without impairing necessary regenerative responses. This review provides a theoretical basis for understanding the pathogenesis of EIMD and for developing targeted strategies to improve skeletal muscle recovery after exercise-induced injury.

ObjectiveTo explore the predictive value of serum cystatin C （CysC） and trabecular bone score （TBS） for postoperative fracture recurrence in elderly patients with osteoporotic vertebral fractures. MethodsA total of 100 elderly patients with osteoporotic vertebral fractures who were treated surgically at Fuling Hospital Affiliated to Chongqing University from June 2022 to June 2023 were followed up for 2 years. They were divided into the poor group （31 cases） and the good group （69 cases） based on the postoperative fracture recurrence. Pearson analysis was used to analyze the correlation between serum CysC and TBS， Cox analysis was used to analyze the influencing factors of postoperative fracture recurrence in elderly patients with osteoporotic vertebral fractures， and ROC analysis was used to analyze the predictive value of serum CysC and TBS for postoperative fracture recurrence in patients. ResultsThe proportion of bone cement penetration and serum CysC in the poor group were significantly higher than those in the good group （χ² = 4.977， P = 0.026； t = 4.749， P = 0.000）， while the proportion of postoperative anti-osteoporosis treatment， bone mineral density T value， and TBS were significantly lower than those in the good group （χ² = 4.229， P = 0.040； t = 2.065， P = 0.042； t = 5.163， P = 0.000）. Serum CysC was negatively correlated with TBS （r = -0.318， P = 0.001）. Elevated serum CysC was a risk factor for postoperative fracture recurrence in elderly patients with osteoporotic vertebral fractures （P < 0.05）， while elevated TBS was a protective factor （P < 0.05）. The AUC of serum CysC for predicting postoperative fracture recurrence in patients was 0.786 （95%CI = 0.679-0.894）， with a sensitivity of 77.42% and a specificity of 71.01%. The AUC of TBS for predicting postoperative fracture recurrence in patients was 0.795 （95%CI = 0.698-0.892）， with a sensitivity of 74.19% and a specificity of 79.71%. The AUC of the combination of serum CysC and TBS for predicting postoperative fracture recurrence in patients was 0.858 （95%CI = 0.773-0.943）， with a sensitivity of 74.19% and a specificity of 82.61%. The combination of the two had a higher predictive value for postoperative fracture recurrence in patients. ConclusionsElderly patients with osteoporotic vertebral fractures who experience postoperative fracture recurrence have elevated serum CysC and decreased TBS. The combination of serum CysC and TBS has a certain predictive value for postoperative fracture recurrence in elderly patients with osteoporotic vertebral fractures.

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.

[Purpose]To investigate the potential causal relationships between serum levels of trace elements and head and neck cancers.[Methods]Single nucleotide polymorphism(SNP)of oral cancer,oropharyngeal cancer,laryngeal cancer and thyroid cancer,associated with calcium,copper,iron,magnesium,zinc,were obtained from genome-wide association studies(GWAS).A two-sample bidirectional Mendelian randomization(MR)analysis was performed using the inverse variance weighting(IVW)method by calculating odds ratio(OR)and 95％confidence interval(CI).Pleiotropy was assessed using MR-PRESSO and MR-Egger regression,and sensitivity analysis was conducted via the"leave-one-out"method.[Results]IVW analysis revealed a causal association between serum magnesium levels and the incidence of oral cancer(OR=0.976,95％CI:0.956～0.997,P=0.025),also between thyroid cancer and serum calcium levels(OR=1.008,95％CI:1.001～1.015,P=0.023).No significant causal associations were observed between other trace ele-ments and head and neck cancers(all P＞0.05).[Conclusion]This MR study suggests that serum magnesium levels serve as a protective factor against oral cancer,while thyroid cancer leads to el-evated serum calcium levels.