ObjectiveTo investigate the protective effect of resveratrol against blood-brain barrier damage in a rat model of cerebral ischemia-reperfusion and to determine whether this effect is mediated by the C-C motif chemokine ligand 3 (CCL3)/C-C chemokine receptor type 5 (CCR5) signaling pathway　Methods　A total of 100 specific pathogen-free (SPF) male Sprague-Dawley (SD) rats, aged 6-8 weeks, were randomly divided into five groups: sham-operated (Sham), model (MCAO), resveratrol-treated (Res), resveratrol+CCR5 agonist (Res+Agonist), and resveratrol+CCR5 antagonist (Res+Antagonist) groups. The MCAO, Res, Res+Agonist, and Res+Antagonist groups were subjected to middle cerebral artery occlusion (MCAO) for 45 min followed by reperfusion to establish the rat model of cerebral ischemia, while the Sham group underwent carotid artery exposure without ischemia. After reperfusion, resveratrol (60 mg/kg) was intraperitoneally injected in Res, Res+Agonist and Res+Antagonist groups, and an equal volume of normal saline was injected in Sham and MCAO groups. Thirty minutes later, CCR5 agonist (20 μg/kg) was injected via the tail vein in the Res+Agonist group, CCR5 inhibitor (1 mg/kg) was injected via the tail vein in the Res+Antagonist group, and the equal volume of normal saline was injected via the tail vein in the Res, Sham and MCAO groups. Thereafter, resveratrol, CCR5 agonist, CCR5 inhibitor, or saline were administered every 24 hours for 3 consecutive days. After modeling, cerebral infarct volume was evaluated by 2,3,5‑triphenyltetrazolium chloride (TTC) staining. Blood‑brain barrier (BBB) permeability was assessed by Evans blue extravasation. Serum levels of the pro‑inflammatory cytokines interleukin‑1β (IL‑1β), tumor necrosis factor‑α (TNF‑α), and CCL3 were measured by enzyme‑linked immunosorbent assay (ELISA). Histopathological changes in brain tissue were observed by hematoxylin and eosin (HE) staining and Nissl staining. Immunofluorescence staining was used to detect the fluorescence intensity of the microglial marker ionized calcium‑binding adapter molecule 1 (Iba‑1) and CCR5. Western blotting analysis was used to detect proteins associated with the CCL3/CCR5 signaling pathway (CCL3, CCR5) in brain tissue, serum pro-inflammatory cytokines [phosphorylated nuclear factor-kappa B (p-NF-κB)] and blood-brain barrier-related proteins [matrix metalloproteinase 9 (MMP9) and occludin]. ResultsCompared with the Sham group, the MCAO group exhibited significantly increased levels of all injury parameters, including cerebral infarct volume, Evans blue extravasation rate in brain tissue, serum levels of the pro‑inflammatory cytokines (IL-1β, TNF-α, and CCL3), the rate of Iba-1- and CCR5-positive immunofluorescence signals in brain tissue, and the protein expression levels of CCL3, CCR5, p-NF-κB, and MMP9 (all P<0.001), accompanied by markedly decreased expression of occludin (P<0.001). HE and Nissl staining revealed pronounced histopathological damage in the MCAO group.Compared with the MCAO group, the Res group showed significant reductions in all the aforementioned injury indicators and a significant increase in occludin expression (P<0.01), together with ameliorated histopathological changes. Compared with the Res group, the Res+Agonist group displayed significantly elevated injury indicators and decreased occludin expression (P<0.05), with aggravated brain tissue damage. In contrast, the Res+Antagonist group exhibited significant decreases in injury indicators and a significant increase in occludin expression (P<0.05), along with further alleviation of histopathological injury. ConclusionResveratrol attenuates peripheral inflammation in cerebral ischemia‑reperfusion injury by targeting the CCL3/CCR5 signaling pathway, thereby exerting a protective effect on the blood‑brain barrier.

Traditional Chinese medicine (TCM) has historically played a pivotal role in the prevention and treatment of warm diseases, establishing a comprehensive theoretical framework that underpins its practices. The distinctive and indispensable contributions of aromatic Chinese herbs in dispelling harmful influences and mitigating the spread of these diseases are well recognized; however, further investigation is warranted to elucidate their systematic properties and regularities, and the theory of aromatic Chinese herbs in preventing and treating warm diseases still needs to be comprehensively summarized. This study employs the principles rooted in TCM, with particular emphasis on the framework for warm diseases. An analysis of the disease mechanisms, transmission dynamics, and preventive strategies is conducted during the early stage of infection, throughout the course of the disease, and in the post-illness phase. Furthermore, the characteristics and applications of aromatic Chinese herbs are integrated with insights drawn from modern pharmacological research to explore their specific roles in the prevention and management of warm diseases. The utilization of aromatic Chinese herbs manifests in a variety of therapeutic effects: aromatic medicinals purging filth and dispelling pathogens for preventing epidemic disease, aromatic medicinals regulation for relieving superficies syndrome and dispersing evils, aromatic medicinals ventilation the lung to relieve cough and asthma, aromatic medicinals resolving the dampness to awaken the spleen and stomach, aromatic medicinals opening the orifices to restore consciousness, aromatic and pungent medicinals to regulate qi, aromatic medicinals dredging the vessels to activate blood circulation and dissipate blood stasis, and aromatic medicinals clearing latent heat from the yin level. These properties facilitate tailored approaches to address the diverse manifestations of warm diseases and their associated symptoms, providing clear guidance for clinical application to achieve pre-disease prevention, active disease treatment, complication prevention, and post-recovery relapse avoidance. The use of aromatic Chinese herbs in preventing and treating warm diseases demonstrates theoretical, practical, systematic, and regular characteristics. The theory of the properties of aromatic Chinese herbs has been expanded and sublimated in clinical practice, and its scientific connotation has been expounded in modern research. Under the guidance of the theory of treatment based on syndrome differentiation, and by taking into account the distinct stages and pathologies of warm diseases, the rational selection of aromatic Chinese herbs can improve the clinical efficacy.

ObjectiveTo investigate the incidence rate of primary liver cancer （PLC） and the progression of liver fibrosis in chronic hepatitis B （CHB） patients with low-level viremia （LLV） （HBV DNA<2 000 IU/mL but ≥20 IU/mL） after treatment adjustment， and to provide more robust evidence for clinical practice. MethodsA retrospective analysis was performed for the clinical data of LLV patients who initially received nucleos（t）ide analogue （NAs） for at least 48 weeks at the Fifth Medical Center of PLA General Hospital from August 2007 to April 2017 and subsequently underwent NAs adjustment due to LLV， and according to the virologic response after 48 weeks of treatment adjustment， the patients were divided into LLV group and complete virological response （CVR） group （HBV DNA<20 IU/mL）. The patients were followed up once every 3‍ ‍—‍ ‍6 months till the primary endpoint event of PLC or October 2024. The incidence rate of PLC and the progression of liver fibrosis were observed， and the progression of liver fibrosis was defined as an increase of ≥1 grade in fibrosis-4 （FIB-4） index. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of PLC， and the Log-rank test was used for comparison between groups； the Cox regression analysis was used to investigate the risk factors for PLC， and the Logistic regression analysis was used to investigate the influencing factors for the progression of liver fibrosis. ResultsA total of 307 patients were enrolled， with a mean age of 50.0 years， and the male patients accounted for 80.5%. After 48 weeks of treatment with the adjusted NAs regimen， 254 patients （82.7%） achieved CVR， and 53 patients （17.3%） still had LLV. For the LLV group， the incidence rate of PLC was 30.2% and the rate of liver fibrosis progression was 22.6%， while for the CVR group， the incidence rate of PLC was only 13.4%， and the rate of liver fibrosis progression was 7.5%. The multivariate regression analyses showed that LLV was an independent risk factor for the onset of PLC （hazard ratio=2.623， 95% confidence interval ［CI］： 1.315‍ ‍—‍ ‍5.234， P=0.006） and the progression of liver fibrosis （odds ratio=3.213， 95%CI： 1.385‍ ‍—‍ ‍7.455， P=0.007）. ConclusionActive adjustment of treatment is needed immediately after the diagnosis of LLV to improve CVR， and if LLV persists after treatment adjustment， it is necessary to enhance the monitoring of liver fibrosis progression and PLC， so as to facilitate early diagnosis and treatment.

Objective:To compare and analyze the differences in positioning errors and placement outside the target area between two different image-guided systems(Halcyon and Synergy)in radiotherapy for cervical cancer.Methods:The data of 40 patients with cervical cancer who received treatment in Dezhou People's Hospital from March 2023 to June 2023 were retrospectively selected.Each patient was treated respectively with Halcyon linear accelerator and Synergy linear accelerator,with 20 cases for each treatment method.All patients underwent cone beam computed tomography(CBCT)at kV level to conduct image scanning before radiotherapy,and the obtained CBCT images were matched with the positioned CT images by online.The registration results of left and right(x),head and foot(y)and front and back(z)of three translation direction,and pitch(Rx),rotation(Ry)and deflection(Rz)directions of rotation direction were respectively obtained.The margin of planning target volume(MPTV)was calculated according to positioning expansion formula.The differences of positioning errors and target area expansion between Halcyon and Synergy image-guided systems were compared and analyzed.Results:Halcyon and Synergy image-guided systems obtained respectively 479 and 447 sets of CBCT images.The translational errors of Halcyon image-guided system on x,y,and z directions were respectively(-0.03±0.21),(0.12±0.63)and(0.02±0.15)cm,and the rotational errors of that on Rx,Ry and Rz directions were respectively(0.38±1.26)°,(-0.40±1.02)°,and(0.07±1.07)°.The translational errors of Synergy image-guided system were respectively(-0.07±0.18),(0.08±0.49)and(0.11±0.22)cm on the three directions,and the rotational errors of that were respectively(0.28±1.29)°,(-0.29±1.29)° and(-0.16±1.20)°.The translational error values on the y direction of both image-guided system were larger than that on x and z directions,and the absolute values of the range of translational errors of them were basically within 5 mm.There were no statistically significant difference in the positioning errors of rotation on Rx and Ry directions between Halcyon and Synergy image-guided systems(P＞0.05),while there was a statistically significant difference in the positioning error of rotation on Rz direction between them(t=-3.06,P＜0.05).The MPTV values of Halcyon image-guided system on x,y and z directions were respectively 0.4,1.4 and 0.3 cm,and those of Synergy image-guided system were respectively 0.4,0.9 and 0.5 cm.The expansion boundary of target area of Halcyon image-guided system on the y direction was larger than that of Synergy image-guided system,and that on other directions were all less or equal to 0.5 cm.Conclusion:The MPTV values of Halcyon and Synergy image-guided systems can meet clinical requirements in radiotherapy.The positioning errors and the tube current of the scan of Halcyon image-guided system were larger than those of Synergy image-guided system,but the scanning time and treatment time of that were significantly lower than those of Synergy image-guided system.Different treatment systems can be selected individually for patients according to their different conditions.

Objective:To explore the molecular mechanism of miR-4508 regulating the inflammatory response of human bronchial epithelial cells induced by representative chrysotile asbestos.Methods:The chrysotile asbestos was ground into ultrafine dust using a horizontal planetary instrument, and human bronchial epithelium (16HBE) cells were taken as the object of infection. Cell survival rate was detected by cell counting kit-8 method, cytotoxicity was detected by lactate dehydrogenase (LDH) kit. The released of inflammatory factor IL-6 was detected by electrochemical luminescence. The released inflammatory factor IL-8 was detected by enzyme-linked immunosorbent assay. The expression level of miR-4508 was screened and verified by reverse transcription-quantitative real-time polymerase chain reaction. After 16HBE cells were treated with AKT inhibitor MK2206, the phosphorylation levels of AKT and PTEN were detected by western blot. The expression levels of AKT and PTEN and the contents of IL-6 and IL-8 were detected in miR-4508 overexpression and interference experiments.Results:With the increase of chrysotile asbestos exposure concentration, the cell survival rate decreased in a concentration-dependent manner, and the LDH content gradually increased. The secretion of IL-6 and IL-8 in chrysotile 25, 50 and 75 μg/ml groups were (325.92±8.61) pg/ml, (331.51±4.96) pg/ml, (378.74±13.77) pg/ml, and (94.95±3.11) pg/ml, (357.60±1.80) pg/ml, (537.19±3.11) pg/ml, respectively, while the group with 0 μg/ml chrysotile was (95.85±1.20) pg/ml and (7.81±0.00) pg/ml ( P＜0.05). In addition, chrysotile asbestos exposure to 16HBE could induce the high expression of miR-4508 . After pretreatment with MK2206, the phosphorylation levels of AKT and PTEN were decreased, the contents of IL-6 and IL-8 were significantly decreased, and the expression level of miR-4508 was significantly reduced. Overexpression of miR-4508 significantly increased the expressions of AKT and PTEN, and the contents of IL-6 and IL-8 ( P＜0.01). After interfering with miR-4508, the expressions of AKT and PTEN were significantly decreased, and the contents of IL-6 and IL-8 were significantly decreased ( P＜0.01). Conclusions:Chrysotile asbestos can induce the inflammatory response of 16HBE cells and up-regulate the expression level of miR-4508. The up-regulation of miR-4508 promotes the 16HBE inflammatory response induced by chrysotile asbestos through the PI3K/AKT pathway.

Vacuum compression molding (VCM) is a novel technology supporting the research and development of pharmaceutical solid dispersions. It is widely applied due to its precision and convenience in sample preparation. This technology integrates the principles of heating, melting, cooling, and vacuum compression to transform solid powders into shaped solids directly. By selecting different molds, temperatures, and pressures, researchers can prepare samples with diverse characteristics. This paper presents an overview of the equipment composition and working principles of VCM technology, demonstrating its distinct advantages in the formulation screening process of amorphous solid dispersions through comparative analysis with hot melt extrusion using case studies, and introduces its applications in the development of drug delivery systems and rheological characterization analysis, with a perspective on the future development of its functions.

Objective To explore the impact of gender factors in participant selection during bioequivalence studies,and to provide insights for improving the screening success rate in subsequent trials.Methods A retrospective study was con-ducted to summarize the screening information of healthy subjects in the bioequivalence study conducted in the Phase Ⅰ Clinical Trial Laboratory of the Affiliated Hospital of Xiangnan University from July 2021 to July 2023.The number of failed screening ca-ses in different stages of screening for each project was counted,and the influence of gender factors on subject screening was ana-lyzed.Results A total of 32 bioequivalence studies involving 2 794 subjects,including 1 816 males and 978 females,were in-cluded in the study.The proportion of males was higher in vital signs and BMI abnormalities,and the proportion of females was higher in ECG abnormalities and active withdrawal,and the pass rate was lower in males than in females(40.0％ vs.45.8％),and the existence of the two was statistically significant(P＜0.05).The results of PC A showed that the distribution of data in males was more dispersed,and the distribution of data in females was centralized,and the two could be clearly differentiated.Binary lo-gistic regression analysis showed significant differences between males and females in laboratory test screening failures and BMI(P＜0.05).Further analysis showed that the screening failure rates of blood biochemistry,urine routine,coagulation function and blood transfusion were higher in males than in females,but the screening failure rates of blood routine were lower than those of fe-males.Conclusions Gender is an important influencing factor in the screening process of bioequivalence studies.Including subjects with appropriate gender ratios can help improve enrollment speed and reduce clinical trial costs.

Objective:To evaluate the clinical efficacy of botulinum toxin type A (BTX-A) injection in enhancing chin aesthetics.Methods:A retrospective analysis was conducted on patients with suboptimal chin aesthetics who underwent dual-plane BTX-A injection at Plastic Surgery Hospital, Chinese Academy of Medical Sciences between August 2023 and March 2024. Prior to injection, patients were instructed to repeatedly pucker their lips forward and upward to identify the most prominent points of the mentalis muscle for injection. A 13 mm 30 G needle was inserted perpendicularly into the muscle layer, and BTX-A was administered at a concentration of 20 U/ml, with 3 U per injection point. For the patients exhibiting significant orange peel signs at rest, intradermal deep-layer BTX-A injection was concurrently performed at a concentration of 5 U/ml, with 0.5 U per linear track. Postoperative follow-up was conducted, and third-party physicians assessed pre- and post-treatment photographs using the global aesthetic improvement scale (GAIS) (scores ranging from 5 to 1, representing worse, no improvement, mild improvement, moderate improvement, and significant improvement, respectively). Patient satisfaction was also surveyed [categorized as very satisfied, satisfied, dissatisfied, or very dissatisfied; satisfaction rate = (very satisfied + satisfied) cases/total cases × 100%], along with their willingness to undergo repeated injections and recommend the procedure to others. Descriptive statistical analysis was performed using SPSS 24.0 software. Normally distributed continuous data were expressed as Mean±SD, and categorical data were expressed as counts (%).Results:A total of 120 patients were included, comprising 11 males and 109 females, aged 22-39 years (mean age of 33.3 years). Follow-up ranged from 1 to 5 months (mean of 1.3 months). Postoperatively, 102 patients reported subjective improvement in chin appearance, characterized by enhanced fullness and roundness of the chin. Thirty-one patients noted a slight elevation of the submental fat pad and improved definition of the cervicomental angle. The mean GAIS score was 1.61±0.78, with 76 cases scoring 1, 24 cases scoring 2, 10 cases scoring 3, and 10 cases scoring 4. Improvement (scores 1-3) was achieved in 91.7% (110/120) of patients. The subjective satisfaction rate was 85.0% (102/120), and 94 patients (78.3%) expressed willingness to undergo repeated injections and recommend the procedure to family or friends. Early postoperative complications included localized bruising in 17 cases, which was resolved within 10 d, and transient fine motor dysfunction of the lower jaw in 23 cases, with normal chewing, swallowing, and facial expressions, all of which were resolved completely within 6 weeks. No cases of mouth deviation, facial paralysis, allergic reactions, or other complications were observed.Conclusion:The application of BTX-A via intramuscular mentalis injection combined with intradermal deep-layer injection significantly improves both dynamic and static chin aesthetics. However, some common complications also ask for the further attention of practitioners.

Objective:To evaluate the clinical value of sacral canal posterior wall reconstruction in the treatment of symptomatic sacral canal cysts.Methods:A retrospective cohort study was conducted.The clinical data of 80 patients with symptomatic sacral cysts who underwent surgical treatment at Beijing Friendship Hospital, Capital Medical University, between June 2018 and September 2024 were collected. There were 19 males and 61 females, with an average age of (49.0±11.3) years (ranged from 23-76 years). The patients were divided into the traditional group ( n=30) and the reconstruction group ( n=50) based on the surgical approach. The traditional group underwent the conventional surgical method without reconstruction of the posterior wall of the sacral canal, while the reconstruction group underwent posterior wall reconstruction of the sacral canal. Postoperative observations included the integrity of the sacral canal posterior wall, wound healing, and symptom improvement in both groups. Measurement data with normal distribution were expressed as mean±standard deviation( ± s). Independent samples t-test was used for comparisons of measurement data between groups. Categorical data were compared using the chi-square test or Fisher′s exact test. Ordinal data were analyzed using the Mann-Whitney U test. Pearson correlation analysis was used to assess the relationship between variables. Results:Among the 80 patients, the sacral bone integrity score in the reconstruction group was (1.42±0.49) scores, compared to (3.00±0.00) scores in the traditional group, the reconstruction group showed significantly better results ( P<0.05). Symptom improvement was also significantly different between the two groups ( P=0.038): in the traditional group, 17 patients experienced complete symptom resolution, 6 partial improvement, 7 no improvement, and 0 worsening; in the reconstruction group, 37 had complete symptom resolution, 11 partial improvement, 2 no improvement, and 0 worsening. The effective improvement rate (complete+ partial improvement) in the reconstruction group was significantly better than that in the traditional group ( P=0.012). In terms of wound healing, 76 cases healed well, 4 had delayed healing, and 0 had infections. In the traditional group, 27 healed well, 3 had delayed healing, 0 infections; in the reconstruction group, 49 healed well, 1 had delayed healing, and 0 infections. There was no significant difference in wound healing rate between the two groups ( P=0.146). A significant positive correlation was found between sacral canal posterior wall integrity and symptom improvement ( r=0.288, P=0.010). Conclusion:Sacral canal posterior wall reconstruction significantly improves postoperative anatomical integrity and clinical outcomes without increasing complications, supporting its adoption as a preferred surgical approach for symptomatic sacral canal cysts.

Objective To investigate the association of liver radiodensity with the degree and progression of liver fibrosis in patients with chronic hepatitis B(CHB).Methods A retrospective cohort study was conducted among 114 CHB patients who were hospitalized in The First Hospital of Lanzhou University from January to December 2019,and related clinical data were collected,including laboratory tests and abdominal CT.The metabolic characteristics of the patients were assessed,and liver radiodensity was measured.An analysis of variance was used for comparison of normally distributed continuous data between three groups,and the Kruskal-Wallis H rank sum test was used for comparison of continuous data with skewed distribution between three groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between three groups.A logistic regression analysis was used to investigate the influencing factors for the degree of liver fibrosis,and the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for the progression of liver fibrosis in CHB.Results Among the 114 patients enrolled,43(37.72％)had no liver cirrhosis,30(26.32％)were suspected of liver cirrhosis,and 41(35.96％)had liver cirrhosis,with a median follow-up time of 538.5(322.75-1 031.50)days.Liver radiodensity on plain scan(odds ratio[OR]=0.81,95％confidence interval[CI]:0.68-0.97,P=0.025),liver radiodensity on contrast-enhanced scan(OR=0.95,95％CI:0.90-0.99,P=0.037),and liver volume(OR=0.99,95％CI:0.98-0.99,P<0.001)were independent influencing factors for the degree of liver fibrosis.The univariate Cox regression analysis showed that the low level of HDL(hazard ratio=2.81,95％CI:1.04-7.54,P=0.041)was associated with the progression of liver fibrosis in CHB patients,and the degree of liver fibrosis,liver volume,and liver radiodensity showed no significant association with the progression of liver fibrosis(all P>0.05).Conclusion In CHB patients,liver radiodensity is an independent influencing factor for the degree of liver fibrosis,and low HDL has a marked influence on the progression of liver fibrosis.