ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective:To investigate the clinicopathological characteristics and molecular variants of chromophobe renal cell carcinoma with small cell components/neuroendocrine-like features (ChRCC-SC/ND-L).Methods:There were 7 cases of ChRCC-SC/ND-L diagnosed by light microscopy and immunohistochemical staining were collected from the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of the People′s Liberation Army Navy (2 cases) between January 2010 and December 2023. The clinical data, histological characteristics, and immunohistochemical staining results of the patients were summarized. Among them, 4 cases underwent whole exome sequencing.Results:Among the 7 cases, 5 cases were male and 2 cases were female. The mean age was 53 (43,58)years,with a range of 36 to 76 years. Gross examination showed that the mean maximum tumor diameter was 7.9 (6.0,9.0) cm,with a range of 5.5 to 13.0 cm. The tumors were nodular, well-defined, gray, red or yellow in color with a solid cut surface, except for 1 case with cystic and solid on cut surface. One case showed visible necrosis, and 1 case invaded the renal pelvis and sinus. Microscopically, the tumors had clear boundaries. Typical ChRCC components (5 cases of classical type, 2 cases of eosinophilic type) were found in all cases, accompanied by varying amounts of small cell components (5%-90%). The two components were mixed in 6 cases or directly adjacent to each other in 1 case. The small cell components were arranged in clusters, dense acinar and nest-like structures, beam-like, fence-like, chrysanthemum-shaped clusters, and ribbon-like patterns. Three cases exhibited patchy necrosis. Intravascular tumor thrombus was found in 1 case. Immunohistochemically, EMA was expressed consistently in the small cell and typical ChRCC components (7/7); whilst both CK7 and CD117 were negative in 1 case with typical ChRCC component (6/7). Small cell components in 3 cases were positive for CD56, whereas all 7 cases were negative for CgA, Syn, and INSM1. The Ki-67 proliferation index was less than 1% in both components. Whole exome sequencing revealed that the 4 cases exhibited different genetic aberrations including 1 case with multiple chromosomal deletions, while 2 cases showed amplification of chromosome 12 and deletion of chromosome 11, respectively. The 7 cases were followed up for 25 to 172 months. Except for 1 patient that died with unknown causes 25 months after surgery, the remaining 6 cases were still alive (average 103.8 months, median 101 months).Conclusions:ChRCC-SC/ND-L is a very rare subtype of ChRCC. The small cell component does not represent true neuroendocrine differentiation and might indicate a morphological heterogeneity of the tumor. The presence of typical chromophobe cell carcinoma components is helpful for the diagnosis of ChRCC-SC/ND-L and they do not have consistent molecular characteristics. ChRCC-SC/ND-L has a good prognosis and the small cell components/neuroendocrine-like components might not have a significant impact on the outcome of patients with the tumor.

Objective:To investigate the clinicopathological characteristics, molecular features, differential diagnosis and prognosis of renal cell carcinoma (RCC) with TFEB gene amplification.Methods:A total of 113 cases of unclassified RCCs and RCCs with TFEB positive expression were collected from the Affiliated Hospital of Qingdao University and Navy 971 Hospital from January 2010 to December 2024. Eight cases of RCCs with TFEB amplification were identified using tissue microarrays, immunohistochemistry, and fluorescence in situ hybridization (FISH) techniques. The clinicopathological data and prognosis of the 8 cases were summarized, and relevant literature was reviewed.Results:Among the 8 cases, there were 5 males and 3 females. The average age was 63.4 (54, 77) year and the median age was 63.5 (59.0, 65.5) year. Seven cases were detected through physical examination, and 1 case presented with initial symptoms of metastasis to bones and lungs. The cohort included 1 biopsy specimen and 7 surgical resection specimens. The tumor diameters ranged from 2.5 to 15.0 cm. The cut surfaces of 5 cases were grayish-yellow or grayish-red, and 2 cases exhibited a colorful appearance, among which 3 cases involved renal sinus and 1 case showed invasion of the perirenal fat tissue. Microscopically, 4 cases were composed of clear cells arranged in solid sheets or acinar structures, along with varying numbers of eosinophilic cells. Two cases exhibited the morphology of high-grade eosinophilic RCC, and 1 case presented biphasic morphology with diffuse polygonal eosinophilic tumor cells and dense small cell components. The remaining 1 case exhibited the morphology of clear cell RCC. According to the WHO/ISUP nuclear grading system, 6 cases were Grade 3 and 2 cases were Grade 2. Multifocal necrosis was observed in 4 cases. In 4 surgical specimens, the tumor tissue invaded the renal parenchyma, with 2 cases showing nodular infiltration to surrounding tissues and 1 case with intravascular tumor thrombus. Immunohistochemical results showed varying degrees of TFEB nuclear positivity in 6 cases (6/8). Melanocytic markers such as Melan A (5/8) and HMB45 (3/8) were expressed at varying degrees. Cathepsin K (6/8), GPNMB (6/8), P504s (7/8) and CD10 (7/8) were positively expressed in most cases. FISH results revealed high-copy amplification of TFEB gene in 4 cases (partially showing clustered amplification) and low-copy amplification in 4 cases. During the follow-up period of 3 to 64 months of the 8 cases, 3 cases metastasized and 2 cases died of disease (both with high-copy TFEB gene amplification).Conclusions:RCC with TFEB gene amplification is rare and exhibits diverse morphological features. A common morphological characteristic of this type of tumor is a mixture of sheet-like clear cells and high nuclear grade eosinophilic cells. Combined immunohistochemical staining for TFEB, melanocytic markers, and GPNMB is helpful for the diagnosis of the tumor, and FISH detection of TFEB gene amplification is the most definitive method in diagnosing this tumor. RCC with TFEB gene amplification usually presents with strong aggressiveness and poor prognosis. Combining surgical resection with immunotherapy or VEGFR-targeted drugs might have therapeutic effects on the tumor.

Objective:To investigate the clinicopathological characteristics and diagnosis of high-grade succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC).Methods:Three cases of high-grade SDH-RCC diagnosed by immunohistochemical staining and/or molecular testing were collected from Affiliated Hospital of Qingdao University and 971 Hospital of Navy of Chinese People′s Liberation Army from January 2015 to December 2023. The clinicopathological characteristics and immunohistochemical features were summarized using light microscopy. Two cases were tested for gene mutations by next-generation sequencing.Results:Of the 3 cases, 2 were male and 1 was female. The ages were 49, 61, and 53 years, respectively. Gross examination revealed that all tumors were single nodules with diameters of 7.0, 4.5, and 5.2 cm, respectively, grayish white in color with irregular borders. Cases 1 and 2 exhibited solid cut sections, whereas case 3 had cystic and solid cut sections. Microscopically, all cases had high WHO/ISUP nuclear grade (3 or 4) and overt invasion. Case 1 exhibited a solid, sheet-like growth pattern with numerous scattered glandular ducts or acinar structures. Case 2 displayed a diffusely growth pattern reminiscent of sarcoma. Case 3 demonstrated intracystic papillary and nodular infiltrative growth patterns. Large clear cytoplasmic vacuoles could be observed in the focal areas of case 1 and case 3. Prominent peritumoral lymphocytes in stroma were noted in case 1. Case 1 was diagnosed with regional lymph node metastasis, and case 2 was diagnosed with renal vein thrombosis. Immunohistochemical staining revealed that SDHB and SDHA were deficiently expressed in 3 cases, while PAX8, FH, and INI-1 exhibited diffuse expression. CD10 (1/3), CA9 (1/3), and CK20 (1/3) were occasionally expressed. The Ki-67 proliferation index ranged from 10% to 50%. Two cases underwent next-generation sequencing and were both found to harbor pathogenic mutations in SDHA (case 2 had a frameshift mutation, and case 3 had a splice site mutation). All 3 cases were followed up for 11 to 112 months. Case 2 died 11 months post-operation, while case 1 and case 3 survived for 19 and 112 months, respectively, without any recurrence or metastasis.Conclusions:High-grade SDH-RCC is a rare subtype of SDH-RCC. The tumor exhibits various architectural patterns and is often misdiagnosed as other types of renal cell carcinoma. The presence of cytoplasmic vacuoles may be indicative for diagnosis. Compared to typical SDH-RCC, the high-grade subtype generally shows a larger tumor size, higher TNM stage, greater invasive potential, and poorer prognosis. For high-grade SDH-RCC, routine SDHB immunohistochemical staining may be necessary. The occurrence of high-grade SDH-RCC may be associated with mutations in SDHA.

OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.

Objective:To investigate the clinicopathological features, diagnosis, and prognosis of renal solitary fibrous tumor (SFT).Methods:Five cases of renal SFT with unequivocal diagnoses at the Affiliated Hospital of Qingdao University between January 2011 and July 2025 were subject to analyses of their clinical, morphological, immunophenotypic, and molecular characteristics, accompanied by a literature review.Results:Two males and three females aged between 45 and 62 years were included, all of whom presented with the discovery of a renal mass during routine physical examinations. Gross examination showed that the five tumors were all confined in the kidney. The tumors were nodular with maximum diameters ranging from 2.5 cm to 11.0 cm (mean, 5.8 cm). Upon cross-sectioning, they exhibited gray-white or gray-yellow cut surface. Histologically, the tumor cells exhibited oval or short spindle shapes in four cases, presenting with varying densities and arranged in short bundles, woven patterns, and irregular formation. Various amounts of coarse collagen and scattered staghorn blood-vessels were found in the stroma. In one case (case 5), the tumor cells were long spindle-shaped, densely organized in bundles, and interwoven, exhibiting inconspicuous boundaries, moderate nuclear atypia, and at least 4 mitotic figures per 10 high-power fields. Irregular patchy collagen deposition was particularly prominent at the edges of the tumor tissue. In two cases (cases 3 and 5), scattered and various amounts of renal tubules were observed in the tumor. Two cases (cases 4 and 5) demonstrated focal invasion of the renal parenchyma, although no necrosis was noted. Immunohistochemical staining showed that the tumor cells were diffusely and strongly positive for vimentin and STAT6 in all 5 cases, and positive for CD34. Bcl-2 positivity was present in 4 of the 5 cases. All cases were negative for CKpan, EMA, PAX8, HMB45, Melan A, SMA, and S-100 protein. The p53 status was wild type, and the Ki-67 index ranged from 1% to 8%. Next-generation sequencing was conducted on one case (case 4), revealing the NAB2 (exon 3)::STAT6 (exon 18) gene fusion. The 5 patients were followed up for 1 to 158 months (mean, 56 months), and all were alive with no recurrence or metastasis.Conclusions:SFT of the kidney are rare and morphologically similar to extrarenal SFT. Key morphological features include short spindle-shaped tumor cells arranged in bundles, interwoven patterns or irregularly, accompanied by staghorn blood-vessels and scattered coarse hyaline collagen fibers. SFT with epithelial inclusions may represent a relatively common histological subtype in the kidney. Immunohistochemical staining that demonstrates diffuse and strong positivity for STAT6 and CD34 is instrumental in diagnosing this tumor. The pathogenesis is linked to the centromeric inversion of chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes. Most of these tumors exhibit favorable prognosis.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.