OBJECTIVE: To study bioactive compounds from the endophytic fungus Penicillium sp. HJT-A-6 isolated from stem of Rhodiola tibetica, and evaluate its allelopathic activity. METHODS: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. In addition, the allelopathic activity of compound 1 was evaluated by measuring the seed germination rate of R. tibetica. RESULTS: Two new polyketides 4-hydroxy-3,6-dimethyl-2H-pyran-2-one (1) and penilactone E (2), together with six known compounds walterolactone A (3), 5-hydroxyhexan-4-olide (4), 3-methyl-2-penten-5-olide (5), chaetoquadrin F (6), (Z)-6-acetyl-3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one (7) and 4-hydroxy-3-(4-hydroxyhexanoyl)-5-methylfuran-2(5H)-one (8) were isolated from Penicillium sp. HJT-A-6. Compound 1 showed moderate seed-germination-promoting activity at a concentration of 0.001 mg/mL while inhibiting the seed germination at concentrations of 0.1 and 0.01 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compound 1 could extend the seed-germination period of R. tibetica (up to 11 d). CONCLUSION Two new compounds were isolated from R. tibetica endophytic fungus Penicillium sp. HJT-A-6. Compound 1 displayed plant hormone-like activity, which inhibited the seed germination of the host plant at high concentrations and promoted the seed germination of the host plant at low concentrations. The results not only enrich the chemical constituents of the endophytic fungi isolated from Rhodiola tibetica, but also provide a theoretical basis for understanding the interaction mechanism between Rhodiola tibetica endophytic fungi and the host plant.

Objective:To investigate the clinicopathological characteristics of well-differentiated papillary mesothelial tumor (WDPMT).Methods:Sixteen cases of resected WDPMTs diagnosed at the Affiliated Hospital of Qingdao University, Qingdao, China from 2017 to 2024 were collected and the clinicopathological features were retrospectively analyzed.Results:There were 7 males amd 9 females, with a mean age of 53.8±14.8 years (range, 25-83 years). Tumor size ranged from 3 to 12 mm in maximum diameter. Of the 16 cases, 15 involved the peritoneum and 1 involved the pleura, one of which occurred on the surface of ovary. All cases were incidentally identified during unrelated surgical procedures. Histologically, tumors exhibited arborizing papillary growth patterns and frequently displayed hierarchically branching papilla. Tumor cells showed cuboidal to flattened cell morphology with minimal nuclear atypia. Mitotic figures were not noted in all cases. Entrapped gland-like tumor cell clusters were found in the stroma of tumor papilla in 1 of the 16 cases. Immunohistochemically, the tumor cells expressed mesothelial markers (Calretinin, D2-40, and CK5/6) in all cases, and BAP1 and MTAP were immunoreactive in all tested cases. Fluorescence in situ hybridization revealed no CDKN2A deletions.Conclusions:WDPMT predominantly occurs in the peritoneum and typically demonstrates indolent biological behaviors. It often shows overlapping features with mesothelioma in situ and epithelioid mesothelioma. The hierarchical branching papillae is its diagnostic hallmark, while routine immunohistochemical evaluation of BAP1 and MTAP is also recommended for differential diagnosis of these tumors.

Carotid artery perivascular adipose tissue (PVAT) can influence plaque formation and progression. Recently, carotid artery PVAT density has emerged as a novel imaging biomarker being capable of reflecting local metabolic and inflammatory states of adipose tissue. It is closely associated with vulnerable plaque characteristics, such as intraplaque hemorrhage, thinning or rupture of the fibrous cap, lipid-rich necrotic core, and calcification. Therefore, carotid artery PVAT density holds promise as a key parameter for early identification of vulnerable carotid plaques and stroke risk prediction. This article reviews the definition and pathophysiological mechanism of PVAT and application of imaging techniques in PVAT, as well as the association between carotid artery PVAT density and vulnerable characteristics of plaques, with the aim of providing references for early identification of asymptomatic high-risk plaques and individualized prevention strategies of ischemic stroke.

Objective To systematically review the risk factors for liver injury in breast cancer patients after chemotherapy.Methods PubMed,Cochrane Library,Embase,Web of Science,CNKI,SinoMed,WanFang Data and VIP databases were electronically searched to collect studies on the influential factors of liver injury in breast cancer patients from inception to March 31,2024.Two reviewers independently screened the literature,extracted data and evaluated the risk of bias of the included studies.Meta-analysis was performed by using RevMan 5.3 software.Results A total of 15 studies involving 6,486 patients were included.The results of Meta-analysis showed that hepatitis B virus infection[OR=2.41,95％CI(1.52,3.82),P＜0.001],lymph node metastasis[OR=1.27,95％CI(1.05,1.55),P=0.02],hyperlipidemia[OR=1.58,95％CI(1.13,2.20)P=0.007],liver metastasis[OR=3.19,95％CI(2.11,4.84),P＜0.001],tumor node metastasis(TNM)stage Ⅲ to Ⅳ[OR=1.49,95％CI(1.17,1.90),P＜0.001],were risk factors for liver injury after breast cancer chemotherapy.Compared with other chemotherapy agents/regimens,the use of fluorouracil[OR=0.58,95％CI(0.42,0.80),P＜0.001],cyclophosphamide[OR=0.65,95％CI(0.47,0.89),P=0.008],AC regimen[OR=0.38,95％CI(0.22,0.66),P＜0.00 1]and neoadjuvant chemotherapy[OR=0.61,95％CI(0.43,0.88),P=0.007]were associated with a lower risk of liver injury,the use of paclitaxel drugs[OR=2.85,95％CI(2.31,3.52),P＜0.001],intensive regimen[OR=3.48,95％CI(2.15,5.62),P＜0.001],TAC regimen[OR=2.42,95％CI(1.38,4.24),P=0.002]increased the risk of liver injury.Tumor TNM stage I[OR=0.63,95％CI(0.51,0.78),P=0.001]were protective factors for liver injury after chemotherapy in breast cancer patients.Conclusion The current evidence shows that multiple factors influence the incidence of liver injury after breast cancer chemotherapy.Medical staff can formulate targeted chemotherapy programs according to the influencing factors and clinical characteristics to reduce the risk of liver injury after chemotherapy.

Bladder-preserving treatment has become a research focus due to its potential to balance therapeutic efficacy and quality of life.In recent years,the rapid development of immunotherapy has brought new opportunities for bladder-sparing strategies.In high-risk non-muscle invasive bladder cancer(HR-NMIBC),emerging regimens such as bacillus calmette-guérin-based immunoenhancement,immuno-chemotherapy combinations,targeted therapy,and gene therapy have demonstrated encouraging efficacy and safety in trials like GU-123 and TRUCE-02,with complete remission rate ranging from 42％-100％.In muscle-invasive bladder cancer(MIBC),immunotherapy is being integrated with trimodal therapy,radiotherapy,chemotherapy,and antibody-drug conjugates,as evidenced by studies such as ReBirth and BTCRC-GU15-023,which reported significant improvements in bladder-intact event-free survival,progression-free survival,and complete remission rate.This review summarizes the latest advances in immunotherapy-based bladder-preserving strategies for both HR-NMIBC and MIBC,aiming to provide insights for future individualized treatment approaches.

Objective:To investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.Methods:The experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups. Results:① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05). Conclusions:Overactivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.

Objective:To investigate impacts of paeoniflorin on inflammation and nuclear transcription factor-κB(NF-κB)/nucleotide-binding oligomeric domain-like receptor protein 3(NLRP3)signal pathway in knee osteoarthritis(KOA)model rats.Meth-ods:SD rats were randomly grouped into model group,glucosamine group,paeoniflorin low-dose group,paeoniflorin high-dose group,paeoniflorin high-dose+phorbol ester(PMA)(NF-κB activator)group,with 10 rats in each group,another 10 rats were regarded as control group,and only knee joint capsule was cut,after treatment with glucosamine,paeoniflorin and PMA,joint pain symptoms of rats were detected by mechanical stimulation method and thermal radiation method;knee joint width,joint swelling and synovial thick-ness were measured;HE staining was applied to detect joint tissue structure and morphology of rats in each group;levels of inflamma-tory factors IL-1β,monocyte chemoattractant protein 1(MCP-1)and IL-9 in joint fluid and serum of rats were detected by ELISA;and Western blot was applied to detect expressions of NF-κB/NLRP3 signal pathway related proteins in rat joint tissue.Results:Com-pared with control group,joint tissue structure of model group was significantly damaged,mechanical pain threshold and thermal sen-sitivity pain threshold were significantly lower(P<0.05),knee joint width,joint swelling and synovial thickness,levels of IL-1β,MCP-1 and IL-9 in joint fluid and serum,and expression of p-NF-κB p65/NF-κB p65 and NLRP3 proteins in joint tissue were higher(P<0.05).Compared with model group,joint tissue damage of rats in glucosamine group,paeoniflorin low-dose group and paeoniflorin high-dose group was reduced,mechanical pain threshold and thermal sensitivity pain threshold were higher(P<0.05),knee joint width,joint swelling and synovial thickness,levels of IL-1β,MCP-1 and IL-9 in joint fluid and serum,and expressions of p-NF-κB p65/NF-κB p65 and NLRP3 proteins in joint tissue were lower(P<0.05);joint tissue injury of rats in paeoniflorin high-dose group was further reduced compared with paeoniflorin low-dose group,mechanical pain threshold and thermal sensitivity pain threshold were further higher(P<0.05),knee joint width,joint swelling and synovial thickness,levels of IL-1β,MCP-1 and IL-9 in joint fluid and serum,and expression of p-NF-κB p65/NF-κB p65 and NLRP3 proteins in joint tissue were further lower(P<0.05).Compared with paeoniflorin high-dose group,joint tissue damage of rats in paeoniflorin high-dose+PMA group was increased,mechanical pain threshold and thermal sensitivity pain threshold were lower(P<0.05),knee joint width,joint swelling and synovial thickness,levels of IL-1β,MCP-1 and IL-9 in joint fluid and serum,and expression of p-NF-κB p65/NF-κB p65 and NLRP3 proteins in joint tissue were higher(P<0.05);there was no significant change in all indexes of rats in glucosamine group(P>0.05).Conclusion:Paeoniflorin can play an anti-inflammatory role by down-regulating the NF-κB/NLRP3 signal pathway,thus alleviating joint injury and joint pain symptoms of KOA rats.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Bladder-preserving treatment has become a research focus due to its potential to balance therapeutic efficacy and quality of life.In recent years,the rapid development of immunotherapy has brought new opportunities for bladder-sparing strategies.In high-risk non-muscle invasive bladder cancer(HR-NMIBC),emerging regimens such as bacillus calmette-guérin-based immunoenhancement,immuno-chemotherapy combinations,targeted therapy,and gene therapy have demonstrated encouraging efficacy and safety in trials like GU-123 and TRUCE-02,with complete remission rate ranging from 42％-100％.In muscle-invasive bladder cancer(MIBC),immunotherapy is being integrated with trimodal therapy,radiotherapy,chemotherapy,and antibody-drug conjugates,as evidenced by studies such as ReBirth and BTCRC-GU15-023,which reported significant improvements in bladder-intact event-free survival,progression-free survival,and complete remission rate.This review summarizes the latest advances in immunotherapy-based bladder-preserving strategies for both HR-NMIBC and MIBC,aiming to provide insights for future individualized treatment approaches.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.