[Application framework and model of Jingjin therapy in rehabilitation medicine].

The Jingjin therapy and rehabilitation medicine share commonalities and complement each other. The application of Jingjin therapy from a rehabilitation perspective can broaden the development path of traditional Chinese medicine (TCM) rehabilitation. This paper, based on relevant literature and research findings, elaborates on the connection between Jingjin syndrome differentiation acupuncture and rehabilitation assessment and treatment. It discusses the application framework of Jingjin's preventive treatment theory in disease prevention and rehabilitation, and forecasts the research model of Jingjin rehabilitation medicine from an integrative perspective of Chinese and western medicine. This study aims to improve the rehabilitation application thinking of Jingjin therapy and enrich the application methods and treatment approaches of TCM rehabilitation medicine.

A novel neuroprotective method against ischemic stroke by accelerating the drainage of brain interstitial fluid.

Ischemic stroke is a leading cause of death and disability worldwide. Inflammatory response after stroke determines the outcome of ischemic injury. A recent study has reported an efficient method, epidural arterial implantation (EAI), for accelerating interstitial fluid (ISF) drainage, which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space (ECS). In this study, the method of EAI was modified (m-EAI) to control its function of accelerating the ISF drainage at different time points following ischemic attack. The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion (tMCAO) rat model. The results demonstrated the accumulation of IL-1ß, IL-6, and TNF-α was significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats, accompanied with decreased infarct volume and improved neurological function. This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS. Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.

Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.

Zr-MOF Carrier-Enhanced Dual-Mode Biosensing Platforms for Rapid and Sensitive Diagnosis of Mpox.

Dual-mode readout platforms with colorimetric and electrochemiluminescence (ECL) signal enhancement are proposed for the ultrasensitive and flexible detection of the monkeypox virus (MPXV) in different scenes. A new nanotag, Ru@U6-Ru/Pt NPs is constructed for dual-mode platforms by integrating double-layered ECL luminophores and the nanozyme using Zr-MOF (UiO-66-NH2) as the carrier, which not only generates enhanced ECL and colorimetric signals but also provide greater stability than that of commonly used nanotags. Dual-mode platforms are used within 15 min from the "sample in" to the "result out" steps, without nucleic acid amplification. The colorimetric mode allows the screening of MPXV with the visual limit of detection (vLOD) of 0.1 pM (6 × 108 copies µL-1) and the ECL mode supports quantitative detection of MPXV with an LOD as low as 10 aM (6 copies·µL-1), resulting in a broad sensing range of 60 to 3 × 1011 copies·µL-1 (10 orders of magnitude). Validation is conducted using 50 clinical samples, which is 100% concordant to those of quantitative polymerase chain reaction (qPCR), indicating that Ru@U6-Ru/Pt NPs-based dual-mode sensing platforms showed great promise as rapid, sensitive, and accurate tools for diagnosis of the nucleic acid of MPXV and other infectious pathogens.

Celiac Axis Stenosis as an Independent Risk Factor for Bile Leakage in Laparoscopic Pancreaticoduodenectomy: A Retrospective Study.

Background: Celiac axis stenosis can potentially lead to insufficient blood supply to vital organs, such as the liver, spleen, pancreas, and stomach. This condition result in the development of collateral circulation between the superior mesenteric artery and the hepatic artery. However, these collateral circulations are often disrupted during pancreaticoduodenectomy (PD), which may increase the risk of postoperative complications. Methods: A retrospective analysis was conducted on patients who underwent laparoscopic pancreaticoduodenectomy (LPD) from April 2015 to April 2023. Celiac trunk stenosis is classified according to the degree of stenosis: no stenosis (<30%), grade A (30%-<50%), grade B (50%-≤80%), and grade C (>80%). The incidence of postoperative complications was evaluated, and both univariate and multivariate risk analyses were conducted. Results: A total of 997 patients were included in the study, with mild celiac axis stenosis present in 23 (2.3%) patients, moderate stenosis in 18 (1.8%) patients, and severe stenosis in 10 (1.0%) patients. Independent risk factors for the development of bile leakage, as identified by both univariate and multivariate analyses, included body mass index (BMI) (HR = 1.108, 95% CI = 1.008-1.218, P = .033), intra-abdominal infection (HR = 2.607, 95% CI = 1.308-5.196, P = .006), postoperative hemorrhage (HR = 4.510, 95% CI = 2.048-9.930, P = <0.001), and celiac axis stenosis (50%-≤80%, HR = 4.235, 95% CI = 1.153-15.558, P = .030), and (>80%, HR = 4.728, 95% CI = .882-25.341, P = .047). Celiac axis stenosis, however, was not determined to be an independent risk factor for pancreatic fistula (P > 0.05). Additionally, the presence of an aberrant hepatic artery did not significantly increase the risk of postoperative complications when compared with celiac axis stenosis alone. Conclusion: Severe celiac axis stenosis is an independent risk factor for postoperative bile leakage following LPD.

Guest-Induced Helical Superstructure from a Gold Nanocluster-Based Supramolecular Organic Framework Enables Efficient Catalysis.

Mimicking hierarchical assembly in nature to exploit atomically precise artificial systems with complex structures and versatile functions remains a long-standing challenge. Herein, we report two single-crystal supramolecular organic frameworks (MSOF-4 and MSOF-5) based on custom-designed atomically precise gold nanoclusters Au11(4-Mpy)3(PPh3)7, showing distinct and intriguing host-guest adaptation behaviors toward 1-/2-bromopropane (BPR) isomers. MSOF-4 exhibits sev topology and cylindrical channels with 4-mercaptopyridine (4-Mpy) ligands matching well with guest 1-BPR. Due to the confinement effect, solid MSOF-4 undergoes significant structural change upon selective adsorption of 1-BPR vapor over 2-BPR, resulting in strong near-infrared fluorescence. Single-crystal X-ray diffraction reveals that Au11(4-Mpy)3(PPh3)7 in MSOF-4 transforms into Au11Br3(PPh3)7 upon ligand exchange with 1-BPR, resulting in 1-BPR@MSOF-6 single crystals with a rarely reported helical assembly structure. Significantly, the double-helical structure of MSOF-6 facilitates efficient catalysis of the electron transfer (ET) reaction, resulting in a nearly 6 times increase of catalytic rates compared with MSOF-4. In sharp contrast, solid MSOF-5 possesses chb topology and cage-type channels with narrow windows, showing excellent selective physical adsorption toward 1-BPR vapor but a nonfluorescent feature upon guest adsorption. Our results demonstrate a powerful strategy for developing advanced assemblies with high-order complexity and engineering their functions in atomic precision.

Utilizing superheated steam to prepare traditional Chinese twice-cooked pork bellies, exploring its effects on the texture and flavor of fat layers.

Fat greatly impacts the overall texture and flavor of pork belly. Twice-cooked pork bellies (TPB), typically boiled and sliced before "back to pot" being stir-fried, is a classic Sichuan cuisine among stir-fried dishes. In this study, the effects of substituting conventional pan-frying (PCV) with superheated steam (SHS) technology on the sensory, texture, microstructure and flavor of the fat layers were investigated. SHS was used as an alternative to boiling (120 °C for 15, 20, 25, and 30 min), and "back to pot" stir-frying was also by SHS. TPB precooked for 25 min (P25) with SHS performed better quality characteristics than PCV, with less collagen fiber disruption and lipid droplet area, resulting in a lower hardness and higher shear force. Besides, the low-oxygen environment of SHS retarded the lipid peroxidation, showing a significantly lower MDA content than PCV. Differently, PCV exhibited more grassy and fatty flavors, while P25 exhibited a unique aroma of fruity and creamy due to its higher UFA/SFA ratios in the pre-cooking stage. Overall, the sensory scores of P25 were comparable to those of PCV (with no significant difference), revealing that SHS is expected to be applied to the industrial production of stir-fried dishes.

Unveiling potential of cellulose gel electrolyte: Molecular engineering for enhanced electrostatic interactions with Mg adatoms in Mg-ion battery.

The Mg-ion battery faces significant limitations due to its liquid electrolyte, which suffers from inherent issues such as leakage and the growth of Mg dendrites. In contrast, gel polymer electrolytes (GPEs) offer heightened safety, a wide voltage window, and excellent flexibility, making them a promising alternative with outstanding electrochemical performance. In this study, a cyano-modified cellulose (CEC) GPE was engineered to aim at enhancing ion transportation and promoting uniform ion-flux through interactions between N and Mg2+ ions. The resulting CEC-based GPE demonstrated a high ionic conductivity of 1.73 mS cm-1 at room temperature. Furthermore, it exhibited remarkable Mg plating/stripping performance (coulombic efficiency ~96.7 %) and compatibility with electrodes. Importantly, when employed in a Mo6S8//Mg battery configuration, the CEC GPE displayed exceptional cycle stability, with virtually no degradation observed even after 650 cycles at 1C, thereby significantly advancing Mg-ion battery technology due to its excellent electrochemical properties. This study provides valuable insights into the molecular engineering of cellulose-based GPEs.

Research progress in the relationship between gut microbiota metabolite trimethylamine N-oxide and ischemic stroke. / è‚ é“èŒç¾¤ä»£è°¢äº§ç‰©æ°§åŒ–ä¸‰ç”²èƒºä¸Žç¼ºè¡€æ€§è„‘å’ä¸­å ³ç³»çš„ç ”ç©¶è¿›å±•.

Ischemic stroke (IS) is a severe cerebrovascular disease that seriously endangers human health. Gut microbiota plays a key role as an intermediate mediator in bidirectional regulation between the brain and the intestine. In recent years, trimethylamine N-oxide (TMAO) as a gut microbiota metabolite has received widespread attention in cardiovascular diseases. Elevated levels of TMAO may increase the risk of IS by affecting IS risk factors such as atherosclerosis, atrial fibrillation, hypertension, and type 2 diabetes. TMAO exacerbates neurological damage in IS patients, increases the risk of IS recurrence, and is an independent predictor of post-stroke cognitive impairment (PSCI) in patients. Current research suggests that the mechanisms of TMAO action include endothelial dysfunction, promoting of foam cell formation, influence on cholesterol metabolism, and enhancement of platelet reactivity. Lowering plasma TMAO levels through the rational use of traditional Chinese medicine, dietary management, vitamins, and probiotics can prevent and treat IS.

Structural basis for transcription activation through cooperative recruitment of MntR.

The manganese transport regulator (MntR) from B. subtilis is a dual regulatory protein that responds to heightened Mn 2+ availability in the cell by both repressing the expression of uptake transporters and activating the expression of efflux proteins. Recent work indicates that, in its role as an activator, MntR binds several sites upstream of the genes encoding Mn 2+ exporters, leading to a cooperative response to manganese. Here, we use cryo-EM to explore the molecular basis of gene activation by MntR and report a structure of four MntR dimers bound to four 18-base pair sites across an 84-base pair regulatory region of the mneP promoter. Our structures, along with solution studies including mass photometry and in vivo transcription assays, reveal that MntR dimers employ polar and non-polar contacts to bind cooperatively to an array of low-affinity DNA-binding sites. These results reveal the molecular basis for cooperativity in the activation of manganese efflux.

Is conventional functional liver remnant volume higher than 40% still sufficient to prevent post-hepatectomy liver failure in jaundiced patients with hilar cholangiocarcinoma? A single-center experience in China.

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.

The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Redox Concomitant Formation Method for Fabrication of Cu(I)-MOF/Polymer Composites with Antifouling Properties.

Marine biofouling, which is one of the technical challenges hindering the growth of the marine economy, has been controlled using cuprous oxide (Cu2O) nanoparticles due to the exceptional antifouling properties of Cu(I) ions. However, Cu2O nanoparticles have encountered bottlenecks due to explosive releases of Cu+ ions, high toxicity at elevated doses, and long-term instability. Here, we present a novel method called Redox Concomitant Formation (RCF) for fabricating a hierarchical Cu(I) metal-organic framework polypyrrole (Cu(I)-MOF/PPy) composite. This method enables in-situ phase transition via successive redox reactions that change the chemical valence state and coordination mode of Cu(II)-MOF, resulting in a new structure of Cu(I)-MOF while creating a PPy layer surrounded by the hierarchical structure. Owing to the steady release of Cu+ ions from the Cu(I) sites and photothermal properties of PPy, Cu(I)-MOF/PPy exhibits superior and broad-spectrum resistance to marine bacteria, algae, and surface-adhered biofilms in complex biological environments, as well as long-term stability, resulting in 100% eradication efficiency under solar-driven heating. Mechanistic insights into successive structural redox reactions and formation using the RCF method are provided in detail, enabling the fabrication of novel MOFs with the desired composition and structure for a wide range of potential applications.

Impaired autophagy-mediated macrophage polarization contributes to age-related hyposalivation.

Age-related dysfunction of salivary glands (SGs) leading to xerostomia or dry mouth is typically associated with increased dental caries and difficulties in mastication, deglutition or speech. Inflammaging-induced hyposalivation plays a significant role in aged SGs; however, the mechanisms by which ageing shapes the inflammatory microenvironment of SGs remain unclear. Here, we show that reduced salivary secretion flow rate in aged human and mice SGs is associated with impaired autophagy and increased M1 polarization of macrophages. Our study reveals the crucial roles of SIRT6 in regulating macrophage autophagy and polarization through the PI3K/AKT/mTOR pathway, as demonstrated by generating two conditional knock out mice. Furthermore, triptolide (TP) effectively rejuvenates macrophage autophagy and polarization via targeting this pathway. We also design a local delivery of TP-loaded apoptotic extracellular vesicles (ApoEVs) to improve age-related SGs dysfunction therapeutically. Collectively, our findings uncover a previously unknown link between SIRT6-regulated autophagy and macrophage polarization in age-mediated hyposalivation, while our locally therapeutic strategy exhibits potential preventive effects for age-related hyposalivation.

Tailoring soy protein/corn zein mixture by limited enzymatic hydrolysis to improve digestibility and functionality.

This study aimed to modify plant protein mixture to improve their functionality and digestibility by limited hydrolysis. Soy protein isolate and corn zein were mixed at the ratio of 5:1 (w/w), followed by limited hydrolysis using papain from 15 to 30 min. The structural characteristics, in vitro digestibility, and functional properties were evaluated. Also, DPPH radical scavenging activity was determined. The results indicated that the molecular weight of different modified samples was largely reduced by limited hydrolysis, and the proportion of random coil was significantly increased. Furthermore, the solubility, foaming, emulsifying and water-holding capacity of hydrolyzed protein mixture were significantly improved, which were close to those of whey protein isolate. In vitro digestibility after 30-min limited hydrolysis was remarkably elevated. In addition, the hydrolyzed protein mixture exhibited a higher antioxidant activity than those of untreated proteins. Overall, limited hydrolysis of protein mixture led to improved digestibility, functionality and antioxidant activity.

Olverembatinib combined with inotuzumab ozogamicin in relapsed refractory Philadelphia chromosome-positive acute lymphoblastic leukemia: A case report.

RATIONALE: Patients with relapsed and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation are at higher risk of relapse and have shorter overall survival. PATIENT CONCERNS: A 31-year-old man presented to the hematology department with intermittent fever and pancytopenia. He was diagnosed with Ph+ acute lymphoblastic leukemia and experienced 2 relapses during treatment. A drug-resistant T315I mutation was detected in the ABL kinase region during review. DIAGNOSES: Morphological examination of the bone marrow revealed approximately 93.5% lymphoid blast. Flow cytometric analysis confirmed the diagnosis of common B-cell ALL with the following phenotype: CD34, CD45dim, CD19, CD10, cCD79a, CD58dim, CD81dim, cTdT, HLA-DR, CD22dim, CXCR4, CD33dim, CD20, CD25, CD13, CD123. The examination of the ABL kinase region mutation suggested a T315I mutation. INTERVENTIONS: Olverembatinib, a third-generation TKI drug, was administered in combination with inotuzumab ozogamicin to treat the disease. OUTCOMES: The patient achieved morphological remission with a negative flow cytometry MRD test, and the quantification of BCR-ABL transcripts was 0% after 1 cycle of therapy. LESSONS: The third-generation TKI olverembatinib has been proven to be effective in CML patients with the T315I mutation, and it may also be effective in Ph+ acute lymphoblastic leukemia. Some new immune drugs have also shown improvement in the remission rate. Combination therapy with olverembatinib and Ino can achieve a complete molecular response in patients with relapsed and refractory Ph+ ALL with the T315I mutation.