ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 （STAT1）/interferon regulatory factor 3 （IRF3） signaling pathway in a pneumonia model induced by lipopolysaccharide （LPS） and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group， and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling， the rats were randomly divided into the model group， dexamethasone group （0.5 mg·kg^-1）， and Yifei Jianpi prescription high-dose （12 mg·kg^-1）， medium-dose （6 mg·kg^-1）， and low-dose （3 mg·kg^-1） groups， with 10 rats in each group. Treatment was administered once daily， and the normal control and model groups received the same volume of normal saline. After 14 days， flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of immunoglobulin G （IgG）， immunoglobulin A （IgA）， immunoglobulin M （IgM）， and the content of tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in alveolar lavage fluid （BALF）. Hematoxylin-eosin （HE） staining was used to observe lung tissue pathology and score the damage. Thymus weight， spleen weight， and wet-to-dry weight ratio （W/D） were recorded. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT1， IRF3， IL-6， and interferon-alpha （IFN-α） in lung tissues， while Western blot was performed to assess the protein expression of STAT1， IRF3， IL-6， and IFN-α. ResultsCompared with the normal control group， the model group showed significantly increased proportion of B lymphocytes in peripheral blood， decreased proportions of NK cells and CD4⁺/CD8⁺ （P<0.05， P<0.01）， decreased serum levels of IgG and IgA， significantly increased IgM levels （P<0.01）， significantly elevated content of TNF-α， IL-6， and IL-8 in BALF， and significantly decreased IL-10 levels （P<0.01）. Lung tissue damage was evident， with significant increases in thymus and spleen weights and a higher W/D ratio （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly upregulated （P<0.05，P<0.01）. Compared with the model group， the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood， increased proportions of NK cells and CD4⁺/CD8⁺ ratios （P<0.05， P<0.01）， significantly increased serum levels of IgG and IgA， significantly decreased IgM levels （P<0.05， P<0.01）， significantly reduced levels of TNF-α， IL-6， and IL-8 in BALF， and significantly increased IL-10 levels （P<0.01）. Lung tissue damage was alleviated， thymus and spleen weights were significantly reduced， and the W/D ratio was markedly decreased （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly downregulated （P<0.05， P<0.01）. ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.

ObjectiveTo investigate the efficacy and safety of stereotactic body radiotherapy （SBRT） combined with sintilimab and bevacizumab in the treatment of patients with unresectable hepatocellular carcinoma （uHCC） and related prognostic factors. MethodsA total of 42 patients with uHCC who underwent SBRT combined with sintilimab and bevacizumab in Department of Radiation Oncology， The Fifth Medical Centre of PLA General Hospital， from March to December 2022 were enrolled. The prescribed dose of planning target volume was 36‍ ‍—‍ ‍50 Gy in 5‍ ‍—‍ ‍6 fractions for continuous irradiation， followed by the regimen of sintilimab and bevacizumab. Each course of treatment was 3 weeks until the presence of tumor progression or serious adverse events. The Kaplan-Meier method was used to calculate overall survival （OS） rate and progression-free survival （PFS） rate， and the log-rank test was used for comparison between groups； the Cox proportional hazards model was used to investigate the influencing factors for prognosis. ResultsThe median follow-up time was 21.6 months， with an objective response rate of 69%， a disease control rate of 85.7%， a median PFS of 10.0 months （95% confidence interval ［CI］： 6.7‍ ‍—‍ ‍13.0）， and a median OS of 23.3 months （95%CI： 14.7‍ ‍—‍ ‍31.8）. Most adverse events were grade 1‍ ‍—‍ ‍2 events， and there were no fatal adverse events. At 6‍ ‍—‍ ‍8 weeks after treatment， the AFP response group had a significantly better OS than the non-AFP response group （not reached vs 11.8 months， P=0.007）. The multivariate analysis showed that AFP response was associated with the good prognosis of patients （hazard ratio=0.31， 95%CI： 0.13‍ ‍—‍ ‍0.75， P=0.009）. ConclusionFor patients with uHCC， SBRT combined with sintilimab and bevacizumab can improve survival with a manageable safety profile， and a >50% reduction in AFP at 6‍ ‍—‍ ‍8 weeks after treatment can be used as a potential prognostic indicator.

OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of primary Sjögren syndrome （pSS）. METHODS Randomized controlled trials （RCTs） on the effects of RTX （trial group） versus placebo （control group） in the treatment of pSS were searched from the Cochran Library， PubMed， Embase， Medline， Web of Science， VIP， CNKI， Wanfang， and other databases during the inception to February 2024. After literature screening and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included， involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index （ESSDAI） score [MD＝－1.17， 95%CI（－1.52， －0.82）， P＜0.000 01] and oral dryness visual analogue scale （VAS） score [MD＝－3.97， 95%CI （－5.08， －2.86）， P＜0.000 01] in the trial group were significantly lower than the control group； unstimulated salivary flow rate [SMD＝0.64， 95%CI（0.41， 0.87）， P＜0.000 01] and Schirmer score [MD＝0.19， 95%CI（0.18， 0.20）， P＜0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD＝0.10， 95%CI（－0.04， 0.23）， P＝0.16]， fatigue VAS score [MD＝－12.50， 95%CI（－35.14， 10.15）， P＝0.28]， European League Against Rheumatism Sjögren syndrome patient reported index （ESSPRI） score [MD＝0.33， 95%CI（－0.53， 1.18）， P＝0.46]， Short-form 36 health survey physical component summary （SF36-PCS） score [MD＝0.90， 95%CI（－2.97， 4.78）， P＝0.65]， SF-36 mental component summary （SF36-MCS） score [MD＝0.11， 95%CI（－0.41， 0.63）， P＝0.68]， total salivary gland ultrasound score [SMD＝－1.91， 95%CI（－4.01， 0.19）， P＝0.07] or the incidence of adverse drug reactions [OR＝1.15，95%CI（0.62，2.13），P＝0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score， unstimulated salivary flow rate， Schirmer score and oral dryness VAS score in pSS patients， and has a good safety profile. However， it did not exhibit significant improvement in fatigue VAS score， ESSPRI score， SF36-PCS score， SF36-MCS score or response rates.

OBJECTIVE To summarize the current situation of pharmaceutical clinic service in our hospital over the past five years， and explore sustainable development strategies for service models of pharmaceutical clinics. METHODS A retrospective analysis was conducted on the consultation records of patients who registered and established files at the pharmaceutical clinic in our hospital from January 2019 to December 2023. Statistical analysis was performed on patients’ general information， medication- related problems， and types of pharmaceutical services provided by pharmacists. RESULTS A total of 963 consultation records were included， among which females aged 20-39 years accounted for the highest proportion （66.04%）； obstetrics and gynecology- related consultations accounted for the largest number of cases. Additionally， 80 patients attended follow-up visits at our hospital’s pharmaceutical clinic. A total of 1 029 medication-related issues were resolved， including 538 cases of drug consultations （52.28%）， 453 medication recommendations （44.02%）， 22 medication restructuring（2.14%）， and 16 medication education （1.55%）； the most common types of medication-related problems identified were adverse drug events（70.07%）. CONCLUSIONS Although the pharmaceutical clinic has achieved recognition from clinicians and patients， challenges such as low awareness among healthcare providers and the public persist. Future efforts should focus on strengthening information technology construction， enhancing pharmacist training， and establishing various forms of outpatient pharmaceutical service models.

ObjectiveTo investigate the effect of astragaloside Ⅳ（AS-Ⅳ） on the proliferation of vascular smooth muscle cells（VSMCs） induced by angiotensin Ⅱ（Ang Ⅱ） based on solute carrier family 7 member 11/glutathione peroxidase 4（SLC7A11/GPX4） pathway. MethodsPrimary rat thoracic aortic VSMCs were cultured by tissue explant method， and the cell types were identified by immunofluorescence. Cell counting kit-8（CCK-8） was used to determine the optimal concentration and time of AS-Ⅳ after Ang Ⅱ stimulation. The experiment was divided into blank group， model group， AS-Ⅳ group（40 μmol·L^-1）， Erastin group（0.5 μmol·L^-1）， Erastin+AS-Ⅳ group（0.5 μmol·L^-1+40 μmol·L^-1）. The blank group was cultured in normal medium， the model group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1）， and each administration group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1） and the corresponding doses of drug. CCK-8 and plate clone formation assay were used to detect the proliferation of cells in each group， Prussian blue staining was used to detect cell iron deposition， the content of reactive oxygen species（ROS） in cells was detected by fluorescence probe method， the content of malondialdehyde（MDA） was detected by thiobarbituric acid（TBA） method， and the protein levels of SLC7A11 and GPX4 in each group were detected by Western blot. ResultsPrimary rat thoracic aortic VSMCs were successfully cultured by tissue explant method， and immunofluorescence detection showed that positive expression of α-smooth muscle actin（α-SMA） and negative expression of vimentin in the cells， identifying them as VSMCs. The optimal concentration and time of AS-Ⅳ determined by CCK-8 were 40 μmol·L^-1 and 24 h， respectively. Pharmacodynamic studies showed that compared with the blank group， the cell proliferation in the model group increased， the iron deposition in the cells increased， the contents of ROS and MDA increased， and the expression levels of SLC7A11 and GPX4 proteins decreased（P<0.05， P<0.01）. Compared with the model group， the cell proliferation of the AS-Ⅳ group was inhibited， the iron deposition in the cells was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. While in the Erastin group， the cell proliferation was increased， the iron deposition was increased， ROS and MDA contents were increased， and the expression levels of SLC7A11 and GPX4 proteins were decreased（P<0.05， P<0.01）. Compared with the AS-Ⅳ group， Erastin+AS-Ⅳ group showed increased cell proliferation， increased iron deposition in cells， increased ROS and MDA contents， and decreased expression of SLC7A11 and GPX4 proteins（P<0.05）. Compared with the Erastin group， the cell proliferation in Erastin+AS-Ⅳ group was inhibited， the iron deposition was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. ConclusionAS-Ⅳ can inhibit ferroptosis by regulating the SLC7A11/GPX4 pathway， so as to weaken the proliferation of VSMCs， thus playing a role in the treatment of atherosclerosis.

AIM: To evaluate the efficacy of 3% diquafosol sodium ophthalmic solution in treating dry eye syndrome following cataract surgery and its impact on tear film stability.METHODS: This prospective clinical study was conducted at Xi'an Aier Eye Hospital, Northwest University from January 2021 to January 2024. A total of 124 patients(124 eyes)who underwent cataract phacoemulsification were enrolled and randomly assigned to either the study group(62 cases, 62 eyes)or the control group(62 cases, 62 eyes)using a random number table. The study group received 3% diquafosol sodium ophthalmic solution four times daily for 1 mo, while the control group was treated with sodium hyaluronate eye drops four times daily for 1 mo. Clinical efficacy, tear film breakup time(BUT), Schirmer I test(SⅠt), corneal fluorescein staining(FL)score, inflammatory factors [interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)] levels in tears, and adverse reactions were compared between the two groups.RESULTS: After treatment, the effective rate was 93.5% in the study group and 87.1% in the control group, with no significant difference between the two groups(P>0.05). The study group showed significantly higher BUT, SⅠt values compared to the control group, while FL score, and inflammatory factor levels in tears were significantly lower at 1 mo after treatment(all P<0.05). The incidence of adverse reactions did not differ significantly between the two groups(P=0.198).CONCLUSION: The 3% diquafosol sodium ophthalmic solution significantly improves tear secretion and tear film stability in patients with dry eye syndrome after cataract surgery, effectively alleviating dry eye symptoms. It is a safe and effective treatment method.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

In January 2025， the European Society for Medical Oncology （ESMO） released the ESMO clinical practice guideline interim update on the management of biliary tract cancer as a supplementary update to Biliary tract cancer： ESMO clinical practice guideline for diagnosis， treatment and follow-up published in November 2022. This interim update mainly revises the latest evidence-based medical recommendations in the key fields of molecular diagnostics and clinical management since the release of the original guidelines， and it is not a comprehensive update of the entire document. This article summarizes and makes an excerpt of the new recommendations from this interim update.

BACKGROUND: Whether lipid-modifying drugs directly impact the outcome of sepsis remains uncertain. Therefore, systematic investigations are needed to explore the potential impact of lipid-related therapies on sepsis outcomes and to elucidate the underlying mechanisms involving circulating inflammatory cytokines, which may play critical roles in the pathogenesis of sepsis. This study aimed to utilize drug-target Mendelian randomization to assess the direct causal effects of genetically proxied lipid-modifying therapies on sepsis outcomes. METHODS: First, a two-sample Mendelian randomization study was conducted to validate the causal associations among high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and sepsis. A subsequent drug-target Mendelian randomization study assessed the direct causal effects of genetically proxied lipid-modifying therapies on the risk of sepsis, sepsis-related critical care admission, and sepsis-related death. The identified lipid-modifying drug targets were subsequently explored for direct causal relationships with 36 circulating inflammatory cytokines. Finally, enrichment analyses of the identified cytokines were conducted to explore the potential relationships of lipid-modifying drugs with the inflammatory response. RESULTS: Genetically proxied cholesteryl ester transfer protein (CETP) inhibitors were significantly associated with sepsis-related critical care admission (OR=0.84, 95% CI [0.74, 0.95], P=0.008,) and sepsis-related death (OR=0.68, 95% CI [0.52, 0.88], P=0.004). The genetically proxied CETP inhibitors were strongly associated with the levels of 15 circulating inflammatory cytokines. Enrichment analyses indicated that CETP inhibitors may modulate inflammatory cytokines and influence the inflammatory response pathway. CONCLUSION: This study supports a causal effect of genetically proxied CETP inhibitors in reducing the risk of sepsis-related critical care admission and death. These findings suggest that the underlying mechanism may involve the modulation of some circulating inflammatory cytokines, influencing the inflammatory response pathway.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.