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 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.

Background Previous studies have demonstrated that the vagus nerve stimulation improves upper limb function in patients with stroke sequelae(six month-two years).This study aimed to investigate whether the auricular intradermal acupuncture(AIA)acted on the auricular branch of the vagus nerve can facilitate the recovery of upper limb motor function and expedite the effects and characteristics of rehabilitation processes in flaccid phase after stroke in Phase Brunnstrom Ⅰ.Methods This study utilized a randomized controlled single-blinded clinical design.Patients with ischemic stroke in Phase Brunnstrom Ⅰ were randomly assigned to the auricular intradermal acupuncture(AIA)group(AIA,standard rehabilitation,conventional acupuncture)or the sham auricular intradermal acupuncture(sham AIA)group(the sham AIA,standard rehabilitation,conventional acupuncture)for 6 days of 1 week(6 times).Primary outcome measures:Brunnstrom(Ueda Assessment),Fugl-Meyer assessment of the upper extremity(FMA-UE)and its subtype score(FMA-UEFS,FMA-UEES),Wolf motor function test scale(WMFT).Secondary outcome measures:Upper limb active range of joint motion(AROM),manual muscle test(MMT)of upper limb muscles,Barthel index(BI).Results Of the 332 patients who were screened,70 patients met the criteria and were recruited.There were 35 patients in the AIA group,1 patient was fall off,34 patients were actually completed;35 patients in the sham AIA group had no falling off case.Primary outcome measures:The upper Ueda assessment of the AIA group were better than those of the sham AIA group after treatment on days 3 and 6(P<0.05,P<0.001,respectively).The FMA-UEFS score on days 6 of the AIA group were significantly better than those of the sham AIA group(P<0.05).FMA-UEES of the AIA group was more associated with FMA-UE than FMA-UEFS with FMA-UE after treatment on day 6(FMA-UEFS:r=0.728,P<0.001;FMA-UEES:r=0.744,P<0.001).After 3 days and 6 days of treatment,the AIA group of the WMFT were significantly improved in the sham AIA group(P<0.05,P<0.001,respectively).Secondary outcome measures:AROM:After 6 days of treatment,the AIA group of shoulder abduction were more improved than in the sham AIA group(P<0.05).MMT:The muscle strength of elbow flexion,and elbow extension muscle improved more in the AIA group than in the sham AIA group(P<0.05).Barthel index(BI):After 6 days of treatment,there was a significant improvement in the group compared with before treatment(P<0.05),but no difference compared with the group(P>0.05).Conclusions AIA combined with conventional rehabilitation and acupuncture,can effectively improve the upper limb motor function of patients with post-ischemic stroke flaccid hemiplegia and accelerates the rehabilitation process of upper limb motor function.Clinical Trial Registration The study protocol is registered withhttp://www.chictr.org.cn(accession number:ChiCTR2200058141).

ObjectiveTo investigate the immunomodulatory effect of polysaccharides from Astragali Radix-Angelicae Sinensis Radix herb pair（Qi-gui polysaccharides） on lipopolysaccharide（LPS）-induced RAW264.7 macrophages and to characterize the structure of the active component Qi-gui homogeneous polysaccharide（AAPS-4a）， and evaluate its protective effect on ulcerative colitis（UC）. MethodsThe effects of six Qi-gui polysaccharides（0.01-100 mg·L^-1） on the proliferation of RAW264.7 cells were assessed by cell proliferation and activity assay（CCK-8）， and enzyme-linked immunosorbent assay（ELISA） was used to investigate the effects of the six polysaccharides（3， 10 mg·L^-1） on the secretion levels of tumor necrosis factor（TNF）-α， interferon（IFN）-β， and nitric oxide（NO） in LPS-induced RAW264.7 cells. After screening for active polysaccharides， high-performance size-exclusion chromatography（HPSEC） was used to determine its homogeneity and relative molecular weight， then its characteristic functional groups were identified by Fourier transform infrared spectroscopy（FT-IR）， monosaccharide composition was analyzed by high performance liquid chromatography（HPLC）， methylation analysis combined with gas chromatography-mass spectrometry（GC-MS） was performed to determine the types and linkage modes of sugar residues， and one- and two-dimensional nuclear magnetic resonance（NMR） were used to identify the sugar residue composition and configuration of the active polysaccharide. Finally， experimental animals were divided into the normal group， model group， AAPS-4a low-dose group（50 mg·kg^-1）， AAPS-4a high-dose group（100 mg·kg^-1）， and sulfasalazine（SASP） group （75 mg·kg^-1）. Except for the normal group， the acute UC mouse model was induced using 3.5% dextran sulfate sodium salt（DSS）. Each treatment group was administered the corresponding dose via oral gavage for 7 days， and changes in body weight were recorded. After treatment， the spleen index and disease activity index（DAI） score were calculated， TNF-α and interleukin-6（IL-6） levels in the serum were detected by ELISA， and histopathological changes in colon tissue were observed by hematoxylin-eosin（HE） staining. ResultsAt the cellular level， AAPS-4a exhibited a dose-dependent inhibition of LPS-induced increases in TNF-α， IFN-β， and NO levels（P<0.01）. Structural characterization of AAPS-4a revealed that it was a homogeneous polysaccharide with a relative molecular weight of 7.6×10³ Da， consisting of mannose（Man）， glucose（Glc）， and galactose（Gal） in a molar ratio of 1.3∶23.9∶1.0. It was primarily composed of five sugar residues of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp， and 1，2-α-D-Galp. In vivo experiments showed that compared with the normal group， the model group demonstrated markedly increased DAI score and spleen index， significantly reduced colon length， and significantly elevated levels of TNF-α and IL-6（P<0.01）. Compared with the model group， the AAPS-4a high-dose group significantly reduced the DAI score and spleen index， as well as TNF-α and IL-6 levels， and improved colonic atrophy（P<0.05， P<0.01）. Pathological observations showed that AAPS-4a significantly inhibited inflammatory cell infiltration in colon tissue and alleviated pathological damage. ConclusionAAPS-4a， a neutral homogeneous polysaccharide composed of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp and 1，2-α-D-Galp， is identified as a key bioactive component contributing to the anti-UC effect of the Qi-gui herb pair. Its immunoregulatory and anti-UC properties suggest its potential as a therapeutic agent for UC.

The theory of five spirits(mind,eternal soul,corporeal soul,consciousness and will)is an important part of traditional Chinese medicine(TCM)theory,which reveals the human mental and psychological activities.Five-spirit theory takes the shape of modern cognitive psychology.Language is an important part of cognitive activities.Under the guidance of the five-spirit theory of TCM,and by combining the research results of modern cognitive psychology,this paper initially constructs a language processing model,and proposes that heart-mind,spleen-consciousness,kidney-will,and liver-soul are all involved in the formation of language.Moreover,the pathogenesis of post-stroke aphasia(PSA)is explored from the perspective of the five spirits.It is proposed that PSA refers to the comorbidity of body and spirit,and its pathogenesis is related to the disorders of the five spirits.After analyzing the clinical manifestations of PSA,it is suggested that malnutrition of heart-mind and insufficient kidney-will contribute to the pathogenesis of auditory comprehension and reading obstacles in patients with PSA,and the deactivation of liver-soul is closely related to spontaneous speech and naming obstacles.The treatment of PSA should be focused on nourishing blood and tranquilizing mind,enhancing consciousness and strengthening will,and suppressing liver to tranquilize soul.And the prescriptions of Pingbu Zhenxin Pills,Zhiyi Decoction plus Dingzhi Pills,and Dinghun Decoction can be chosen for modified use.The acupuncture and moxibustion can also be used for PSA,by performance mainly on the acupoints of heart meridians,pericardial meridians,spleen meridians,kidney meridians and liver meridians.The syndrome differentiation and treatment system for PSA with the combination of Chinese medicine and acupuncture based on the five-spirit theory makes up for the shortcomings of stress on the physique while ignorance of the spirit in the conventional zang-fu organ syndrome differentiation,and expands the methods for early intervention of PSA with TCM and approaches to improve the prognosis of rehabilitation.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective To investigate the application value of bedside ultrasound measurement of gastric antrum cross-sectional area(CSA)combined with acute gastrointestinal injury ultrasound(AGIUS)score in guiding early individualized enteral nutrition therapy for sepsis patients.Methods From January 2023 to July 2024,61 sepsis patients meeting diagnostic criteria were enrolled and divided into an observation group(n=30)and a control group(n=31).The observation group underwent bedside ultrasound monitoring of gastric antrum CSA to calculate gastric residual volume(GRV)and AGIUS score for formulating individualized en-teral nutrition strategies.The control group used gastric tube withdrawal method for GRV measurement to guide enteral nutrition.Clinical baseline characteristics,enteral nutrition-related complications,nutritional/in-fection indicators,and disease severity parameters were compared between groups.Predictive efficacy was ana-lyzed using receiver operating characteristic(ROC)curve and area under the curve(AUC).Results Both groups showed gradual increases in enteral nutrition feeding rates and total volumes over time,with the obser-vation group demonstrating significantly higher values than the control group at each time point(P＜0.05).The observation group started nasogastric feeding earlier than the control group(P＜0.05).Target calorie a-chievement rates on day 3,5,and 7 were better in the observation group(P＜0.05).The incidence of feeding intolerance progressively decreased in the observation group but increased in the control group over day 1,3,and 5,with significant intergroup differences at each time point(P＜0.05).By day 7,the observation group exhibited significantly higher prealbumin(PA),albumin(ALB),and transferrin(TF)levels compared to day 1 and the control group(P＜0.05).Both groups showed reductions in APACHE Ⅱ,SOFA,and AGI scores by day 7,with the observation group displaying significantly lower scores than the control group(P＜0.05).The observation group had shorter ICU stays[(10.83±3.26)d vs.(14.55±3.14)d,P＜0.05].The combination of gastric antrum CSA measurement and AGIUS scoring demonstrated excellent predictive value for feeding intolerance(AUC=0.920,95％CI:0.848-0.963),with 95.50％sensitivity and 82.50％specificity,achieving 87.60％predictive accuracy.Conclusion Bedside ultrasound measurement of gastric antrum cross-sectional area(CSA)combined with AGIUS scoring shows good effect as a safe and effective monitoring modality for guiding early individualized enteral nutrition therapy in sepsis patients.

Objective:This study aimed to propose an innovative modular surgical technique and explore its safety and application value in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy for advanced proximal gastric cancer invading the greater curvature.Methods:A retrospective collection was conducted on 34 patients with proximal gastric cancer invading the greater curvature who underwent laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy in the same center from October 2020 to December 2022. The technical key points, precautions and crucial steps of the modular surgical technique were summarized, and the Clinical indicators were analyzed.Results:All 34 patients successfully completed the operation under laparoscopy without conversion to open surgery. The average operation duration was 151.9±4.1 minutes, and the duration of splenic hilar lymphadenectomy was 12.9±1.5 minutes. The median intraoperative blood loss was 50(20, 50) ml, and the blood loss during splenic hilar lymphadenectomy was 5 (2, 5) ml. The median number of harvested lymph nodes was 32.0 (23.5,39.5), and the number of submitted No.10 lymph nodes was 3 (2, 4). The metastasis rate of No.10 lymph nodes was 20.6% (7/34). No patient had intraoperative complications. During the postoperative hospital stay, one patient had incision infection (Clavien-Dindo I), and one patient had pulmonary infection (Clavien-Dindo II). The time for the first postoperative feeding was 3 (2, 5) days, the time for the first postoperative flatus was 2 (2,3) days, the time for the first postoperative defecation was 3 (3, 4) days, the total postoperative drainage volume was 1047.5 (607.5,1397.5) mL, the time for postoperative drainage tube removal was 7 (6, 9) days, and the length of postoperative hospital stay was 7.0 (6.0, 9.5) days.Conclusions:The application of the innovative modular surgical technique in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy can simplify surgical process and enable safe, precise and comprehensive dissection of splenic hilar lymph nodes.

Background Previous studies have demonstrated that the vagus nerve stimulation improves upper limb function in patients with stroke sequelae(six month-two years).This study aimed to investigate whether the auricular intradermal acupuncture(AIA)acted on the auricular branch of the vagus nerve can facilitate the recovery of upper limb motor function and expedite the effects and characteristics of rehabilitation processes in flaccid phase after stroke in Phase Brunnstrom Ⅰ.Methods This study utilized a randomized controlled single-blinded clinical design.Patients with ischemic stroke in Phase Brunnstrom Ⅰ were randomly assigned to the auricular intradermal acupuncture(AIA)group(AIA,standard rehabilitation,conventional acupuncture)or the sham auricular intradermal acupuncture(sham AIA)group(the sham AIA,standard rehabilitation,conventional acupuncture)for 6 days of 1 week(6 times).Primary outcome measures:Brunnstrom(Ueda Assessment),Fugl-Meyer assessment of the upper extremity(FMA-UE)and its subtype score(FMA-UEFS,FMA-UEES),Wolf motor function test scale(WMFT).Secondary outcome measures:Upper limb active range of joint motion(AROM),manual muscle test(MMT)of upper limb muscles,Barthel index(BI).Results Of the 332 patients who were screened,70 patients met the criteria and were recruited.There were 35 patients in the AIA group,1 patient was fall off,34 patients were actually completed;35 patients in the sham AIA group had no falling off case.Primary outcome measures:The upper Ueda assessment of the AIA group were better than those of the sham AIA group after treatment on days 3 and 6(P<0.05,P<0.001,respectively).The FMA-UEFS score on days 6 of the AIA group were significantly better than those of the sham AIA group(P<0.05).FMA-UEES of the AIA group was more associated with FMA-UE than FMA-UEFS with FMA-UE after treatment on day 6(FMA-UEFS:r=0.728,P<0.001;FMA-UEES:r=0.744,P<0.001).After 3 days and 6 days of treatment,the AIA group of the WMFT were significantly improved in the sham AIA group(P<0.05,P<0.001,respectively).Secondary outcome measures:AROM:After 6 days of treatment,the AIA group of shoulder abduction were more improved than in the sham AIA group(P<0.05).MMT:The muscle strength of elbow flexion,and elbow extension muscle improved more in the AIA group than in the sham AIA group(P<0.05).Barthel index(BI):After 6 days of treatment,there was a significant improvement in the group compared with before treatment(P<0.05),but no difference compared with the group(P>0.05).Conclusions AIA combined with conventional rehabilitation and acupuncture,can effectively improve the upper limb motor function of patients with post-ischemic stroke flaccid hemiplegia and accelerates the rehabilitation process of upper limb motor function.Clinical Trial Registration The study protocol is registered withhttp://www.chictr.org.cn(accession number:ChiCTR2200058141).

Objective:This study aimed to propose an innovative modular surgical technique and explore its safety and application value in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy for advanced proximal gastric cancer invading the greater curvature.Methods:A retrospective collection was conducted on 34 patients with proximal gastric cancer invading the greater curvature who underwent laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy in the same center from October 2020 to December 2022. The technical key points, precautions and crucial steps of the modular surgical technique were summarized, and the Clinical indicators were analyzed.Results:All 34 patients successfully completed the operation under laparoscopy without conversion to open surgery. The average operation duration was 151.9±4.1 minutes, and the duration of splenic hilar lymphadenectomy was 12.9±1.5 minutes. The median intraoperative blood loss was 50(20, 50) ml, and the blood loss during splenic hilar lymphadenectomy was 5 (2, 5) ml. The median number of harvested lymph nodes was 32.0 (23.5,39.5), and the number of submitted No.10 lymph nodes was 3 (2, 4). The metastasis rate of No.10 lymph nodes was 20.6% (7/34). No patient had intraoperative complications. During the postoperative hospital stay, one patient had incision infection (Clavien-Dindo I), and one patient had pulmonary infection (Clavien-Dindo II). The time for the first postoperative feeding was 3 (2, 5) days, the time for the first postoperative flatus was 2 (2,3) days, the time for the first postoperative defecation was 3 (3, 4) days, the total postoperative drainage volume was 1047.5 (607.5,1397.5) mL, the time for postoperative drainage tube removal was 7 (6, 9) days, and the length of postoperative hospital stay was 7.0 (6.0, 9.5) days.Conclusions:The application of the innovative modular surgical technique in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy can simplify surgical process and enable safe, precise and comprehensive dissection of splenic hilar lymph nodes.