Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

OBJECTIVE: To explore the effects of electroacupuncture (EA) on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells (GCs) in patients with polycystic ovary syndrome (PCOS) and phlegm-dampness syndrome. METHODS: In this randomized controlled trial, 90 infertile women with PCOS and phlegm-dampness syndrome were recruited between August 2022 and December 2022. Patients were randomly assigned to the EA and control groups using a random sequence of codes in the order of enrolment, with 45 in in each group. Both groups underwent the ovarian stimulation protocol. The patients in the EA group received EA therapy including Zhongwan (CV 12), Qihai (CV 6), bilateral Xuehai (SP 10), Sanyinjiao (SP 6), Yinlingquan (SP 9), Tianshu (ST 25), Zusanli (ST 36), and Fenglong (ST 40), and the patients in the control group was treated with pseudo-acupuncture. The intervention was 25 min twice a week for a total of 6 times until the trigger day after menstruation had ended in the cycle before oocyte retrieval. The primary outcomes were clinical pregnancy rate (CPR) and the number of high-quality embryos. The secondary outcomes were (1) pregnancy-related indicators, including fresh embryo transfer rate (ETR), ovarian hyperstimulation syndrome (OHSS) rate, early pregnancy loss rate (ePLR), ectopic pregnancy rate, live birth rate (LBR), and cumulative CPR; (2) mitochondrial autophagy and mitochondrial membrane potential (MMP) in GCs; and (3) scoring for Chinese medicine syndrome. Adverse events to assess clinical safety were also monitored. RESULTS: The cumulative CPR was significantly higher in the EA group (42/45, 93.3%) than in the control group (38/45, 84.4%, P=0.036). The number of high-quality embryos and fresh ETR in the EA group were higher than those in the control group (3.80±1.65 vs. 2.44±1.34, P<0.001; 46.7% vs 24.4%, P=0.028). Ectopic pregnancies were not observed in either group. There were no significant differences in the fresh CPR, OHSS rate, ePLR or LBR between the two groups (P>0.05). Compared with the control group, the EA group showed lower expression levels of miR-146a-5p mRNA and P62 protein in GCs and higher levels of MMP and the LC3-II/LC3-I protein ratio (all P<0.01). The phlegm-dampness syndrome scores of the EA group were significantly lower than those of the control group (P<0.01). CONCLUSIONS EA significantly improved pregnancy outcomes in patients with PCOS and phlegm dampness syndrome. Mechanistically, this effect may be related to EA in decreasing miR-146a-5p mRNA expression, promoting mitochondrial autophagy in GCs, and improving mitochondrial function, which may contribute to improved oocyte quality. (Trial registration No. ChiCTR2200062915).
Humans ; Female ; Polycystic Ovary Syndrome/therapy* ; Pregnancy ; Electroacupuncture ; Granulosa Cells/metabolism* ; Adult ; Mitochondria/metabolism* ; Pregnancy Outcome ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Infertility, Female/therapy*

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

OBJECTIVE To investigate the role of glyceraldehyde-3-phosphate dehydrogenase(GAPDH)in regulating ferroptosis,malignant biological behavior,and cisplatin resistance in laryngeal squamous cell carcinoma(LSCC)under hypoxic conditions.METHODS Human laryngeal cancer Hep-2 and TU212 cell lines were cultured in vitro under hypoxic(1%O2)and normoxic(21%O2)conditions without serum.Hep-2 cells were divided into five experimental groups:DMSO control group,Erastin treatment group,Hypoxia+Erastin group,Hypoxia+Erastin+NC-GAPDH group,and Hypoxia+Erastin+Silenced GAPDH group,to study the cellular response under various experimental conditions.Quantitative polymerase chain reaction(qPCR)and Western blot(WB)techniques were employed to analyze GAPDH mRNA and protein expression levels in each cell line.Cell Counting Kit-8(CCK-8),colony formation,and Transwell invasion assays were used to assess the vitality,proliferation,and invasion capabilities of each group of laryngeal cancer cells.Additionally,CCK-8 assays were used to determine cell resistance to various concentrations of cisplatin(5,15,20 μg/ml).Kit methods were used to evaluate intracellular malondialdehyde(MDA)and glutathione(GSH)levels.WB was employed to detect the expression levels of glutathione peroxidase 4(GPX4)and 4-hydroxynonenal(4-HNE)proteins.Fe2+probes and reactive oxygen species(ROS)fluorescence probes were used to measure intracellular Fe2+content and ROS levels.Transmission electron microscopy was utilized to observe mitochondrial morphology changes to assess ferroptosis occurrence.RESULTS Compared to normoxic conditions,hypoxia significantly increased the expression of GAPDH mRNA and protein in Hep-2 and Tu212 cells(P<0.05).Under hypoxic conditions,the number of cell colonies,migration capacity,and cell viability at 15 and 20 μg/ml cisplatin treatment were significantly higher than those under normoxic conditions(P<0.05).When GAPDH was silenced,these hypoxia-induced enhancements were reversed.Under normoxic conditions,compared to the DMSO control group,Erastin treatment significantly reduced the number of colonies,migration capacity,and cell viability at 15 and 20 μg/ml cisplatin treatment(P<0.05).However,under hypoxic conditions,the inhibitory effect of Erastin was weakened.Additionally,in the hypoxia+Erastin+si-GAPDH group,the number of colonies,migration capacity,and cell viability at 15 and 20 μg/ml cisplatin treatment were significantly lower than those in the hypoxia+Erastin+NC-GAPDH group(P<0.05).CONCLUSION This study reveals that silencing GAPDH under hypoxic conditions can reverse the inhibition of ferroptosis in LSCC cells,thereby suppressing their malignant biological behavior and cisplatin resistance.

Objective To explore the distribution patterns of tongue and pulse manifestations and traditional Chinese medicine(TCM)syndrome elements in ischemic stroke(IS)patients of different genders and ages,thus to provide approaches for the prevention and treatment of stroke with TCM.Methods The criteria of six syndrome elements in Diagnostic Scale of Syndrome Elements in Ischemic Stroke were used for the comprehensive identification of syndrome elements in 5 254 cases of inpatients confirmed as IS at the first visit in Shenzhen Traditional Chinese Medicine Hospital from 2017 to 2023.Moreover,the tongue proper,tongue coating,and whose pulse manifestations ranking in the top five in terms of the frequency of occurrence were collected for comparison and analysis.Results(1)For the distribution of TCM syndrome elements in 5 254 cases of IS patients,phlegm-dampness syndrome was the most common syndrome type(3 544 cases,67.5%),and then came qi deficiency syndrome(653 cases,12.4%)and yin deficiency syndrome(453 cases,8.6%).There were statistically significant differences in the distribution of phlegm-dampness syndrome,internal heat syndrome,and yin deficiency syndrome between the male and the female(P＜0.01).And the distribution of phlegm-dampness syndrome,qi deficiency syndrome,internal wind syndrome,and internal heat syndrome in the youth differed from that in the middle-aged and elderly(P＜0.01).(2)The tongue and pulse manifestations in IS patients with the leading six detection rates which ranked in descending order of frequency of occurrence were as follows:dull tongue(1 993 cases,37.9%),dark red tongue(1 907 cases,36.3%),thin and white coating(1 885 cases,35.9%),wiry and slippery pulse(1 714 cases,32.6%),white and greasy coating(1 679 cases,32.0%),and wiry and thready pulse(1 609 cases,30.6%).The detection rates of tongue and pulse manifestations such as light red tongue,thin and white coating in the youth group were significantly higher than those in the middle-aged and elderly group,and the detection rates of dark red tongue,and tooth-marked tongue in the middle-aged and elderly group were significantly higher than those in the youth group,the differences all being statistically significant(P＜0.05).The female patients had higher detection rates of dull tongue,thin and white coating,thin and yellow coating,wiry and thready pulse,and deep and thready pulse than male patients,while the male patients had higher detection rates of dark red tongue,red tongue,white and greasy coating,yellow and thick-greasy coating,white and thick-greasy coating,wiry and slippery pulse,and slippery pulse than the females,and the differences were all statistically significant(P＜0.05 or P＜0.01).Higher detection rate of thin and white coating was shown in the youth female than that in the youth male,while higher detection rate of wiry and slippery pulse was shown in the youth male than that in the youth female,and the differences were all statistically significant(P＜0.05 or P＜0.01).The middle-aged and elderly female patients had higher detection rates of dull tongue,thin and white coating,wiry and thready pulse,and deep and thready pulse than the middle-aged and elderly male patients,while the middle-aged and elderly male patients had higher detection rates of dark red tongue,red tongue,white and greasy coating,white and thick-greasy coating,yellow and thick-greasy coating,wiry and slippery pulse,and slippery pulse than the middle-aged and elderly female patients,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Phlegm-dampness syndrome,qi deficiency syndrome,and yin deficiency syndrome exert a significant effect on IS,and phlegm-dampness syndrome is the most common syndrome type.Factors such as gender and age have influences on the distribution of TCM syndrome in patients with IS.

Objective:To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED).Methods:Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed.Results:Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases.Conclusions:CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Objective:To investigate the changes in the white matter fiber structure of fetal brain with mild to moderate isolated ventriculomegaly (IVM) using diffusion tensor imaging (DTI) model and fixed based analysis (FBA) method of diffusion MRI (dMRI).Methods:This was a case-control study. Twenty fetuses diagnosed with mild to moderate IVM who were admitted to the Provincial Hospital Affiliated to Shandong First Medical University from August 2022 to August 2023 were included prospectively as the IVM group, with gestational age ranging from 24 to 36 (29.9±3.6) weeks. The control group included 22 normal control fetuses obtained from the dMRI atlas data of Chinese fetal brain, with gestational age ranging from 24 to 36 (30.2±3.7) weeks. The dMRI data were collected for all fetuses and the DTI model was used to obtain fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity of 7 main fiber bundles, including the genu and splenium of the corpus callosum, middle cerebellar peduncle, bilateral cortico-spinal tract, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. The FBA method was used to obtain fiber density (FD), fiber cross-sectional area (FC), and fiber density and cross-section (FDC) of the whole brain. The comparison of DTI parameters of each fiber bundle between the two groups was conducted using independent sample t test or Mann-Whitney U test. The comparison of FBA parameters between the two groups was performed using covariance analysis, and the MRtrix3 software package was used to display the brain regions with significant differences. Results:The FA values of the inferior longitudinal fasciculus in the IVM group and the control group were 0.142±0.012 and 0.133±0.015, respectively, and the difference was statistically significant ( t=2.21, P=0.033), while the DTI parameters of the other fiber bundles showed no statistically significant differences ( P>0.05). The whole brain FBA results showed that compared with the control group,FD decreased while FC increased in the corpus callosum, fornix, and sagittal stratum in IVM fetuses, while FDC decreased in the cortico-spinal tract. Conclusion:There are microstructural changes of the brain white matter fiber in intrauterine fetuses with mild to moderate IVM, which are mainly located in the white matter fiber bundles surrounding the body, atrium, and temporal horn of the lateral ventricle.

A new crinane-type alkaloid, 6-epihydroxypowelline (1), together with six known alkaloids, lycorine (2), 2-O-acetyllycorine (3), deacetylbowdensine (4), 1-epideacetylbowdensine (5), 8-demethyl-3-oxomaritidine (6), and (-)-marithamine (7) were isolated from the whole parts of the Crinum latifolium L. in Vietnam. The structure identification of all compounds was determined by 1D, 2D-NMR as well as HR-ESI-MS spectroscopic techniques. The absolute configuration of these compounds was established by the ECD data. In addition, in vitro inhibition of acetylcholinesterase (AChE) activities was assessed for all isolated alkaloids. All alkaloids had AChE inhibitory effects, with IC50 values ranging from 32.65 ± 2.72 to 212.76 ± 8.30 µM and compound 3 displayed the strongest inhibition of AChE, with IC50 values of 32.65 ± 2.72 µM (in comparison to the reference drug, galanthamine, which had an IC50 of 2.40 ± 0.45 µM).