ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

With the rising incidence of colon cancer, several studies have indicated that aquaporin 1 (AQP1) expression is associated with the development of colon cancer. This study aims to elucidate the potential molecular mechanisms between them. Methods: We screened data from The Cancer Genome Atlas (TCGA) database and retrospectively examined AQP1 protein expression in 127 colon cancer patients to analyze the relationship between AQP1 expression and pathological stages, prognosis. We created stable colon cancer cell lines with differential AQP1 expression, the effect of AQP1 expression on the proliferation and migration of colon cancer cells was assessed by in vitro and in vivo studies, and explored potential molecular mechanisms through Western blotting. Results: High AQP1 expression was associated with poorer survival (overall survival [OS], p = .028) in colon cancer patients from the TCGA database. Similarly, retrospective clinical data indicated that high AQP1 expression was associated with reduced disease-free survival and OS (p = .036 and p = .017, respectively). The low-expressing AQP1 colon cancer cells exhibited a decrease in proliferation and migration ability of colon cancer cells compared to the overexpressing AQP1 group (p < .05) in vitro and in vivo. Immunohistochemistry and western blotting experiments validated heightened expression of N-cadherin, vimentin, and claudin- 1 in the tumor tissues of the overexpressing AQP1 group. Conversely, reduced AQP1 expression resulted in decreased expression of claudin- 1. Conclusions: AQP1 correlates with unfavorable prognosis in colon cancer and potentially enhances the proliferation and migration of colon cancer by up-regulating claudin-1 expression.

Lianpo Yin was first recorded in the Revised Treatise on Cholera from Suixi Residence by WANG Mengying. It is composed of seven medicinal herbs： Coptidis Rhizoma， Magnoliae Officinalis Cortex， Sojae Semen Praeparatum， Acori Tatarinowii Rhizoma， Pinelliae Rhizoma， Gardeniae Fructus， and Phragmitis Rhizoma. As one of the classic prescriptions for clearing heat， resolving dampness， regulating Qi， and harmonizing the middle energizer， it has been included in the Catalogue of Ancient Classic Prescriptions （Second Batch： Han Chinese Medicine） published by the National Administration of Traditional Chinese Medicine in 2023. Lianpo Yin is primarily indicated for cholera caused by the accumulation of dampness-heat， and it can promote digestion and eliminate phlegm. By summarizing the ancient literature records， chemical constituents of individual herbs and the compound formula， pharmacological effects， and modern clinical applications of Lianpo Yin， this paper discovers that the understandings of most ancient physicians are consistent with the original text. The pathogenesis treated by this prescription is generally attributed to the accumulation of dampness-heat in the middle energizer and disrupted ascending and descending of Qi. The main chemical components of this prescription include coptisine， trigonelline， genistein， palmatine， berberine， honokiol， and magnolol. Lianpo Yin exhibits pharmacological effects such as anti-inflammatory activity， regulation of apoptosis， modulation of mitochondrial autophagy， regulation of the hypothalamic-pituitary-adrenal （HPA） axis， promotion of gastrointestinal motility， improvement of the gastric mucosal barrier， regulation of intestinal flora and their metabolites， and antimicrobial activity. In modern clinical practice， this prescription is mainly used to treat digestive system diseases such as chronic superficial gastritis and Helicobacter pylori （Hp）-associated gastritis. Additionally， it demonstrates significant therapeutic effects on various diseases affecting the nervous， respiratory， dermatological， and cardiovascular systems. This study provides a detailed review of the ancient literature records， chemical components， pharmacological effects， and clinical applications of Lianpo Yin and its modified formulas， aiming to offer references for the dosage form development and broader clinical application of this classic prescription.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， with a complex pathogenesis. Mitochondria play a pivotal role in this disease process， and studies have confirmed that mitochondrial dysfunction can exacerbate metabolic disorders and induce innate immune imbalance， while mitochondrial DNA （mtDNA） is the core molecule mediating these two pathological effects. After the abnormal release of mtDNA， it can be recognized by intracellular pattern recognition receptors， which in turn triggers innate immune responses and causes tissue damage， forming a pathological pathway of “mtDNA release-immune activation-tissue damage”. Currently， there is a lack of systematic reviews summarizing the mechanism of action of this pathway in different stages of MAFLD and the intervention strategies targeting this pathway. This article systematically reviews the core molecular mechanism of this pathway， its pathological role in the development and progression of MAFLD， and the current intervention strategies targeting this mechanism， in order to provide a theoretical basis for analyzing the pathogenesis of MAFLD and developing novel therapeutic strategies.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective:To investigate the efficacy of using a single Kocher-Langenbeck approach to improve anterior column screw fixation for the treatment of transverse + posterior wall acetabular fractures.Method:A retrospective analysis was conducted of the data of 21 patients who had been treated with a single Kocher-Langenbeck approach to improve anterior column screw fixation for transverse + posterior wall acetabular fractures at Department of Orthopaedics, Weifang People's Hospital from May 2021 to May 2023. There were 11 males and 10 females with an age of (51.3±15.5) years. The time from injury to surgery was (10.4±3.6) days. The anterior column screw fixation was improved as follows: screws were implanted 1 to 2 cm in front of the apex of the great notch of the external iliac plate of the pelvis to penetrate out at the upper branch root of the pubic ramus, with the whole screw fully located within the bony channel. Such indexes were recorded as surgical time, intraoperative blood loss, intraoperative fluoroscopy frequency for improved placement of anterior column screws, fracture healing time, incidence of complications, and fracture reduction and hip joint function at the last follow-up.Results:For this cohort, surgical time was (120.9±40.7) minutes, intraoperative blood loss (330.2±65.9) mL, and intraoperative fluoroscopy frequency for improved placement of anterior column screws (6.2±2.3) times. The 21 patients were followed up for (21.5±5.9) months. All fractures achieved bony union after (3.2±1.1) months. Incision fat liquefaction occurred in 1 patient after surgery and symptoms of sciatic nerve injury were observed in 2 patients. Follow-ups observed no such complications as loosening or breakage of internal fixators. According to the Matta scoring criteria, the quality of fracture reduction at the last follow-up was evaluated as anatomical reduction in 15 cases, as satisfactory reduction in 4 cases, as acceptable reduction in 2 cases, giving a satisfaction rate of 90.5% (19/21). According to the improved Merle d'Aubigné & Poster scoring criteria, hip function was evaluated as excellent in 16 cases, as good in 2 cases, and as fair in 3 cases, giving an excellent and good rate of 85.7% (18/21).Conclusion:It is effective to use a single Kocher-Langenbeck approach to improve anterior column screw fixation for the treatment of transverse + posterior wall acetabular fractures, showing advantages of reduced surgical time and intraoperative bleeding.

Objective To use AI-assisted motor dysfunction assessment for quantitative evaluation of motor function in Parkinson's disease(PD)and multiple system atrophy-Parkinsonian type(MSA-P)in order to achieve accurate differential diagnosis.Methods A total of 105 participants aged ≥60 years were consecutively enrolled from the First and Third Medical Centers of Chinese PLA General Hospital between January and September 2024.Based on diagnostic criteria,they were divided into a PD group(48 cases),a MSA-P group(31 cases),and a control group(26 cases).The general information was collected,and the motor function was evaluated with Move-ment Dysfunction Assessment Software in order to assess the diagnostic value of the AI-assisted assessment in differentiating between PD and MSA-P.Results Significantly differences were observed among the three groups in terms of facial expression indicators,bilateral finger tapping frequency,bilateral hand movement frequency,right hand movement amplitude change rate,bilat-eral palm flipping frequency,bilateral toe tapping frequency,freezing load of bilateral toe tapping,bilateral leg flexibility frequency,right leg flexibility amplitude change rate,freezing load of bilat-eral leg flexibility,upright extension angular velocity,turnaround time,forward step frequency,backward step frequency,forward average stride length,backward average stride length,forward average walking speed,backward average walking speed,forward average step width,backward average step width,bilateral postural tremor frequency,bilateral postural tremor maximum am-plitude,bilateral action tremor frequency,bilateral action tremor maximum amplitude,and com-parison of bilateral resting tremor frequency(P＜0.05,P＜0.01).The MSA-P group exhibited significantly lower blink frequency,maximum amplitude and frequency of facial tremors,upright extension angular velocity,and step frequency,while higher ratio of mouth opening duration and longer turnaround time when compared with the PD group(P＜0.05,P＜0.01).The AUC value of the combined nine motor function indicators and the five facial expression indicators in differ-entiating PD from MSA-P was 0.943(95％CI:0.895-0.991,P=0.000)and 0.925(95％CI:0.870-0.981,P=0.000),respectively,both better than that of individual indicators.Conclusion Combi-nation assessment of facial expression,posture,gait with AI assistance can contribute to the dif-ferential diagnosis of PD and MSA-P.