The regulation of intestinal flora on host's genes may play an essential role in the development of endometrial hyperplastic processes in yang deficiency individuals.

Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.

Efficacy of TNF-α Inhibitors in the Treatment of nr-axSpA: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

INTRODUCTION: A growing number of randomized controlled trials (RCTs) have demonstrated the effectiveness of tumor necrosis factor-α (TNF-α) inhibitors in treating non-radiographic axial spondyloarthritis (nr-axSpA). This study aimed to evaluate the efficacy of TNF-α inhibitors in the treatment of nr-axSpA. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were systematically searched for relevant RCTs using specific keywords up to June 2023. The primary outcome was the proportion of patients who achieved Assessment in SpondyloArthritis international Society 40% (ASAS40). Secondary outcomes included ASAS20, Bath Ankylosing Spondylitis Disease Activity Index 50% (BASDAI50), ASAS partial remission, and ASAS5/6. RESULTS: A total of eight RCTs involving 1,376 patients were included. Patients receiving anti-TNF therapy exhibited a higher rate of ASAS40 (pooled RR = 2.36; 95% CI: 1.63-3.42; p < 0.001). In addition, the TNF-α inhibitor group showed higher BASDAI50 rates (pooled RR = 2.06; 95% CI: 1.48-2.89), ASAS20 rates (pooled RR = 1.48; 95% CI: 1.31-1.67), ASAS partial remission rates (pooled RR = 2.33; 95% CI: 1.58-3.43), and ASAS5/6 rates (RR = 3.46; 95% CI: 2.05-5.83) than the placebo group. CONCLUSION: The TNF-α inhibitors were effective in treating nr-axSpA.

Effects of immunogenic cell death-inducing chemotherapeutics on the immune cell activation and tertiary lymphoid structure formation in melanoma.

Background: The infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas. Methods: Doxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining. Results: Doxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8+ T cells and tissue-resident memory T cells (TRM) and an increase in the secretion of interferon-γ, granzyme B, and perforin in CD8+ T subsets and activation of B cells and dendritic cells. Doxorubicin alone and in combination with gemcitabine decreased regulatory T cells in the TIME. Moreover, doxorubicin treatment promoted the formation of HEV and TLS. Doxorubicin treatment also upregulated the expression of programmed cell death protein (PD)-1 in CD8+ T cells and programmed cell death protein ligand (PD-L)1 in tumor cells. Conclusions: These results indicate that doxorubicin with an ICD reaction promotes TLS formation and increases PD-1/PD-L1 expression in tumor tissues. The results demonstrate the development of a therapeutic avenue using combined immune checkpoint therapy.

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke.

BACKGROUND: Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis. METHODS: Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis. RESULTS: The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p < 0.001). Conversely, no statistically significant differences were observed for CD163 between the groups. The presence of Sema7A/CD163 did not show any associations with stroke severity or hemorrhagic transformation (all p > 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301-3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252-5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity. CONCLUSION: This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.

An ACC-VTA-ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences.

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACCGlu) projecting to the VTA indirectly inhibit dopaminergic neurons (VTADA) by activating local GABAergic interneurons (VTAGABA), and this effect is reinforced after nerve injury. VTADA neurons in turn project to the ACC and synapse to the initial ACCGlu neurons to convey feedback information from emotional changes. Thus, an ACCGlu-VTAGABA-VTADA-ACCGlu positive-feedback loop mediates the progression to and maintenance of persistent pain and comorbid anxiodepressive-like behavior. Disruption of this feedback loop relieves hyperalgesia and anxiodepressive-like behavior in a mouse model of neuropathic pain, both acutely and in the long term.

Intramuscular injection of palmitic acid-conjugated Exendin-4 loaded multivesicular liposomes for long-acting and improving in-situ stability.

BACKGROUND: Exendin-4 (Ex4) is a promising drug for diabetes mellitus with a half-life of 2.4 h in human bodies. Besides, the Ex4 formulations currently employed in the clinic or under development have problems pertaining to stability. In this study, palmitic acid-modified Ex4 (Pal-Ex4) was prepared and purified to extend the half-life of Ex4. In addition, Pal-Ex4-MVLs were further designed and optimized as a long-acting delivery system for intramuscular injection. METHODS: Pal-Ex4 was encapsulated within multivesicular liposomes (MVLs) via a two-step double emulsification process. The formulated products were then assessed for their vesicle size, encapsulation efficiency, and in vitro and in vivo. RESULTS: Pal-Ex4-MVLs with a notable encapsulation efficiency of 99.18% were successfully prepared. Pal-Ex4-MVLs, administered via a single intramuscular injection in Sprague-Dawley rats, sustained stable plasma concentrations for 168 h, presenting extended half-life (77.28 ± 12.919 h) and enhanced relative bioavailability (664.18%). MVLs protected Ex4 through providing stable retention and slow release. This approach considerably improved the in-situ stability of the drug for intramuscular administration. CONCLUSIONS: The combination of palmitic acid modification process with MVLs provides dual protection for Ex4 and can be a promising strategy for other hydrophilic protein/polypeptide-loaded sustained-release delivery systems with high drug bioactivity.

Genome-wide identification and expression profiling of the WRKY gene family reveals abiotic stress response mechanisms in Platycodon grandiflorus.

The WRKY family of transcription factors (TFs) is an important gene family involved in abiotic stress responses. Although the roles of WRKY TFs in plant abiotic stress responses are well studied, little is known about the stress-induced changes in WRKY family in Platycodon grandiflorus. 42 PgWRKY genes in seven subgroups were identified in the P. grandiflorus genome. The content of eight platycodins in P. grandiflorus was investigated under cold, heat, and drought stresses. Platycodin D levels significantly increased under three abiotic stresses, while the content changes of other platycodins varied. Transcriptome analysis showed that different WRKY family members exhibited varied expression patterns under different abiotic stresses. PgWRKY20, PgWRKY26, and PgWRKY39 were identified as three key candidates for temperature and drought stress responses, and were cloned and analysed for sequence characteristics, gene structure, subcellular localisation, and expression patterns. The RT-qPCR results showed that PgWRKY26 expression significantly increased after heat stress for 48 h, cold stress for 6 h, and drought stress for 2 d (DS_2 d). The PgWRKY39 expression level significantly increased at DS_2 d. This study provides a theoretical basis for clarifying the molecular mechanism of the abiotic stress responses of the WRKY gene family in P. grandiflorus.

Identification and functional characterization of two trans-isopentenyl diphosphate synthases and one squalene synthase involved in triterpenoid biosynthesis in Platycodon grandiflorus.

MAIN CONCLUSION: Two trans-isopentenyl diphosphate synthase and one squalene synthase genes were identified and proved to be involved in the triterpenoid biosynthesis in Platycodon grandiflorus. Platycodon grandiflorus is a commonly used traditional Chinese medicine. The main bioactive compounds of P. grandiflorus are triterpenoid saponins. The biosynthetic pathway of triterpenoid saponins in P. grandiflorus has been preliminarily explored. However, limited functional information on related genes has been reported. A total of three trans-isopentenyl diphosphate synthases (trans-IDSs) genes (PgFPPS, PgGGPPS1 and PgGGPPS2) and one squalene synthase (SQS) gene (PgSQS) in P. grandiflorus were screened and identified from transcriptome dataset. Subcellular localization of the proteins was defined based on the analysis of GFP-tagged. The activity of genes was verified in Escherichia coli, demonstrating that recombinant PgFPPS catalysed the production of farnesyl diphosphate. PgGGPPS1 produced geranylgeranyl diphosphate, whereas PgGGPPS2 did not exhibit catalytic activity. By structural identification of encoding genes, a transmembrane region was found at the C-terminus of the PgSQS gene, which produced an insoluble protein when expressed in E. coli but showed no apparent effect on the enzyme function. Furthermore, some triterpenoid saponin synthesis-related genes were discovered by combining the component content and the gene expression assays at the five growth stages of P. grandiflorus seedlings. The accumulation of active components in P. grandiflorus was closely associated with the expression level of genes related to the synthesis pathway.

Calculation of Mechanical Properties, Electronic Structure and Optical Properties of CsPbX3 (X = F, Cl, Br, I).

We utilized a first-principle density functional theory for a comprehensive analysis of CsPbX3 (X = F, Cl, Br, I) to explore its physical and chemical properties, including its mechanical behavior, electronic structure and optical properties. Calculations show that all four materials have good stability, modulus of elasticity, hardness and wear resistance. Additionally, CsPbX3 demonstrates a vertical electron leap and serves as a semiconductor material with direct band gaps of 3.600 eV, 3.111 eV, 2.538 eV and 2.085 eV. In examining its optical properties, we observed that the real and imaginary components of the dielectric function exhibit peaks within the low-energy range. Furthermore, the dielectric function gradually decreases as the photon energy increases. The absorption spectrum reveals that the CsPbX3 material exhibits the highest UV light absorption, and as X changes (with the increase in atomic radius within the halogen group of elements), the light absorption undergoes a red shift, becoming stronger and enhancing light utilization. These properties underscore the material's potential for application in microelectronic and optoelectronic device production. Moreover, they provide a theoretical reference for future investigations into CsPbX3 materials.

Prevalence of high blood pressure and its associated factors among students in Shenyang, China: A cross-sectional study.

There is growing evidence that the prevalence of high blood pressure is increasing, and it may have serious consequences. However, research on the prevalence and influencing factors of high blood pressure among primary and secondary school students is still relatively scarce. This study aims to investigate the prevalence and influencing factors of high blood pressure among primary and secondary school students in Shenyang, in order to provide scientific evidence for the prevention and management of this disease. From April to May 2020, 4892 students aged 7 to 17 years were selected as the survey subjects, and on-site physical measurements and questionnaire surveys were conducted. The prevalence of high blood pressure was described. Restricted cubic spline was used to analyze the dose-response relationship between sleep duration, BMI and the risk of high blood pressure. Logistic regression was used to analyze the risk factors. Multiplicative and additive models were used to analyze the interaction between sleep duration and BMI. The results showed that the overall prevalence of high blood pressure among students aged 7 to 17 years in Shenyang was 9.9%, with a higher prevalence in females than males (12.1% vs 7.9%) and in urban areas than suburban areas (11.8% vs 7.7%). The prevalence was lowest in students with normal weight (8.3%) and highest in those who were obese (12.5%). The prevalence fluctuated to some extent among different age groups, but overall, it increased with age, with the lowest prevalence in primary school students (7.0%), 11.4% in mild school students, and the highest prevalence of 14.3% in high school students. Multivariable analysis showed that the risk of high blood pressure in female students was 1.90 times higher than that in male students (95% CI: 1.54-2.35), and the risk in suburban areas was 0.65 times lower than that in urban areas (95% CI: 0.52-0.81). Students with a BMI ≥ 21 kg/m2 had a 1.58 times higher risk than those with a BMI < 21 kg/m2(95% CI: 1.28-1.96), while those with a sleep time ≥ 8 hours had a 0.80 times lower risk than those with a sleep time < 8 hours (95% CI: 0.65-0.99). Exercise can significantly reduce the risk of high blood pressure, while using electronic devices for more than 0.5 hours significantly increases the risk of high blood pressure. BMI and sleep duration have no interaction effect on the risk of high blood pressure. To reduce the prevalence of high blood pressure, students should reduce the use of electronic devices, ensure adequate exercise, maintain a reasonable weight, and ensure sufficient sleep.

Insights into the Acid-Induced Gelation of Original Pectin from Potato Cell Walls by Gluconic Acid-δ-Lactone.

The acid-induced gelation of pectin in potato cell walls has been gradually recognized to be related to the improvement in the cell wall integrity after heat processing. The aim of this study was to characterize the acid-induced gelation of original pectin from a potato cell wall (OPP). Rheological analyses showed a typical solution-sol-gel transition process of OPP with different additions of gluconic acid-δ-lactone (GDL). The gelation time (Gt) of OPP was significantly shortened from 7424 s to 2286 s. The complex viscosity (η*) of OPP gradually increased after 4000 s when the pH was lower than 3.13 and increased from 0.15 to a range of 0.20~6.3 Pa·s at 9000 s. The increase in shear rate caused a decrease in η, indicating that OPP belongs to a typical non-Newtonian fluid. Furthermore, a decrease in ζ-potential (from -21.5 mV to -11.3 mV) and an increase in particle size distribution (from a nano to micro scale) was observed in OPP after gelation, as well as a more complex (fractal dimension increased from 1.78 to 1.86) and compact (cores observed by cryo-SEM became smaller and denser) structure. The crystallinity of OPP also increased from 8.61% to 26.44%~38.11% with the addition of GDL. The above results call for an investigation of the role of acid-induced OPP gelation on potato cell walls after heat processing.

Characteristics of net ecosystem exchange and source distribution of Xilinhot grassland, China.

To understand carbon sequestration capacity of grasslands, the changes of CO2 flux in Xilinhot grasslands and the influence of environmental factors were analyzed by using the eddy data of Xilinhot National Climate Observatory in 2018-2021, and the distribution of flux source areas was analyzed. The results showed that the southwest wind prevailed in the study area throughout the year, the source area in the growing season was larger than that in the non-growing season, and the source area under stable atmospheric conditions was larger than that under unstable conditions. The maximum length of source region with a contribution rate of 90% was close to 400 m, which was consistent with the length estimated by the classical law. The net ecosystem exchange (NEE) of Xilinhot grasslands had obvious diurnal and seasonal dynamics, which was manifested as a carbon sink in the daytime and a carbon source at night during the growing season and weak carbon source in the non-growing season. From 2018 to 2021, the annual total NEE were -15.59, -46.28, -41.94, and -78.14 g C·m-2·a-1, respectively, with an average value of -45.49 g C·m-2·a-1, indicating that Xilinhot grassland had strong carbon sequestration capacity. Vapor pressure deficit and photosynthetically active radiation helped grasslands absorb atmospheric CO2. At night, when temperature was above 0 ℃, the increases in air and soil temperature promoted vegetation respiration to release CO2.

Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction.

BACKGROUND AND PURPOSE: Previous studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI. METHODS: In a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge). RESULTS: We evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05). CONCLUSIONS: Sacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.

Dual-responsive PEG-lipid polyester nanoparticles for siRNA and vaccine delivery elicit anti-cancer immune responses by modulating tumor microenvironment.

Cancer vaccine-based immunotherapy has great potential; however, the vaccines have been hindered by the immunosuppressive tumor microenvironment (TME). In this study, dual-responsive PEG-lipid polyester nanoparticles (PEG BR647-NPs) for tumor-targeted delivery were proposed. PEG BR647-NPs containing the model tumor-associated antigen (TAA) OVA and the signal transduction and activator of transcription 3 (STAT3) siRNA were delivered to the tumor. The PEG BR647-NPs were internalized by tumor-associated dendritic cells (TADCs), where the TAA and siRNA were released into the cytoplasm via the endo/lysosome escape effect. The released OVA was presented by the major histocompatibility complex class I to activate T cells, and the released STAT3 siRNA acted to relieve TADC dysfunction, promote TADC maturation, improve antigen-presenting ability, and enhance anticancer T cell immunity. Meanwhile, the PEG BR647-NPs were ingested by tumor cells, killing them by the pro-apoptosis effect of STAT3 siRNA. Moreover, PEG BR647-NPs could reduce the proportion of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in tumors and abrogate immunosuppression. The integration of relieved TADC dysfunction, promoted TADC maturation, enhanced antigen cross-presentation, abrogated immunosuppression, and improved pro-apoptosis effect boosted the vaccination for tumor immunotherapy. Thus, PEG BR647-NPs efficiently delivered the vaccine and STAT3 siRNA to the tumor and modulated immunosuppressive TME, thus providing better antitumor effects.

Mitochondrial dynamics-related genes DRP1 and OPA1 contributes to early diagnosis of cognitive impairment in diabetes.

BACKGROUND AND AIM: DRP1 and OPA1 play important roles in mitochondrial fusion and fission. However, the role of DRP1 and OPA1 amplification in mitochondrial cognitive impairment has not been reported. This study aimed to investigate the relationship between DRP1 and OPA1 and the risk of cognitive impairment. METHODS: In this study, 45 elderly patients with diabetes admitted to the Lianyungang Second People's Hospital from September 2020 to January 2021 were included. The patients were divided into normal group, mild cognitive impairment group and dementia group by using MMSE score, and the clinical characteristics of the three groups were compared. The amplification multiples of the two genes' DNA were calculated by ΔΔCT and defined as 2- K. Spearman rank correlation was used to analyze the correlation between the DNA amplification multiples of patients' DRP1 and OPA1 and AD8 and MoCA scores. The sensitivity and specificity of DNA amplification multiples of DRP1 and OPA1 to predict clinical outcomes of diabetic cognitive impairment were evaluated using Receiver operator characteristic (ROC) curves. Multiple logistic regression was used to evaluate the relationship between DNA amplification factor of DRP1 and OPA1 and cognitive function. RESULTS: DRP1(2- K) and OPA1(2- K) significantly increased and decreased in dementia and MCI groups compared with the normal group (P ≤ 0.001). The DNA amplification factor of DRP1 was positively correlated with AD8 score and negatively correlated with MoCA score (P < 0.001). The DNA amplification factor of OPA1 was positively correlated with the MoCA score (P = 0.0002). Analysis of ROCs showed that the DNA amplification factor of OPA1 had a higher predictive value for dementia (P < 0.0001), and that it had a higher predictive value when used in combination with DRP1. Multiple logistic regression results showed that increased DNA amplification in DRP1 was associated with increased risk of dementia (OR 1.149;95%CI,1.035-1.275), and increased DNA amplification in OPA1 was associated with decreased risk of MCI (OR 0.004;95%CI,0.000-0.251) and dementia (OR 0.000;95%CI,0.000-0.134). CONCLUSION: DNA amplification multiples of DRP1 and OPA1 are associated with the risk of dementia in elderly patients and may serve as potential biomarkers.

Use of local wound infiltration in open hepatectomy to reduce wound pain: A systematic review and meta-analysis.

The aim of this study was to assess the effects of local wound infiltration anaesthesia on postoperative wound pain in patients undergoing open liver resection. The Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang databases were searched. The search period spanned from database creation to December 2022. All relevant studies on local wound infiltration anaesthesia for analgesia after hepatectomy were included. Two investigators independently screened the literature, extracted data and evaluated the quality of each study. Review Manager (RevMan) 5.4 software (Cochrane Collaboration) was used for the meta-analysis, in which 12 studies with 986 patients were included. The results show that local wound infiltration anaesthesia effectively reduced surgical site wound pain at 4 h (mean difference [MD]: -1.26, 95% confidence intervals [CIs]: -2.15 to -0.37, P = .005), 12 h (MD: -0.84, 95% CIs: -1.26 to -0.42, P < .001), 24 h (MD: -0.57, 95% CIs: -1.01 to -0.14, P = .009) and 48 h (MD: -0.54, 95% CIs: -0.81 to -0.26, P < .001) postoperatively; however, there was no significant difference in analgesia at 72 h postoperatively (MD: -0.10, 95% CIs: -0.80 to 0.59, P = .77). These findings suggest that local wound infiltration anaesthesia administered to patients undergoing open liver resection provides good postoperative wound analgesia at the surgical site.

Dissimilatory sulfate reduction in an anaerobic biofilm reactor for tofu processing wastewater treatment: Bacterial community and their functional genes.

Dissimilatory sulfate reduction (DSR) is the key sulfur cycle that transforms sulfate to sulfide. This process leads to odour issues in wastewater treatment. However, few studies have focused on DSR during treating food processing wastewater with high sulfate. This study investigated DSR microbial population and functional genes in an anaerobic biofilm reactor (ABR) treating tofu processing wastewater. The tofu processing wastewater is a common food processing wastewater in Asia. The full-scale ABR was operated for over 120 days in a tofu and tofu-related products manufacturing factory. Mass balance calculations based on the reactor performance indicated that 79.6-85.1 % of the sulfate was transformed into sulfide irrelevant to dissolved oxygen supplementation. Metagenomic analysis revealed 21 metagenome-assembled genomes (MAGs) containing enzymes encoding DSR. The biofilm contained the complete functional genes of DSR pathway in the full-scale ABR, indicating that biofilm could process DSR independently. Comamonadaceae, Thiobacillus, Nitrosomonadales, Desulfatirhabdium butyrativorans, Desulfomonile tiedjei were the dominant DSR species in the ABR biofilm community. Dissolved oxygen supplementation directly inhibited DSR and mitigated HS- production. It was also found that Thiobacillus contained all the function genes encoding every necessary enzyme in DSR, and thus Thiobacillus distribution directly correlated to DSR and the ABR performance.

Thyroid hormone levels paradox in acute ischemic stroke.

Objective: Accumulating evidence has suggested that thyroid hormone levels affect the prognosis of acute ischemic stroke (AIS), but the results have been inconsistent. Methods: Basic data, neural scale scores, thyroid hormone levels, and other laboratory examination data of AIS patients were collected. The patients were divided into excellent and poor prognosis group at discharge and 90 days after discharge. Logistic regression models were applied to evaluate the relationship between thyroid hormone levels and prognosis. A subgroup analysis was performed based on stroke severity. Results: A number of 441 AIS patients were included in this study. Those in the poor prognosis group were older, with higher blood sugar levels, higher free thyroxine (FT4) levels, and severe stroke (all p < 0.05) at baseline. Free thyroxine (FT4) showed a predictive value (all p < 0.05) for prognosis in the model adjusted for age, gender, systolic pressure, and glucose level. However, after adjustment for types and severity of stroke, FT4 showed insignificant associations. In the severe subgroup at discharge, the change in FT4 was statistically significant (p = 0.015), odds ratio (95% confidence interval) = 1.394 (1.068-1.820) but not in the other subgroups. Conclusions: High-normal FT4 serum levels in patients with severe stroke receiving conservative medical treatment at admission may indicate a worse short-term prognosis.

Immune desert in MMR-deficient tumors predicts poor responsiveness of immune checkpoint inhibition.

Background: Although many efforts have been devoted to identify biomarkers to predict the responsiveness of immune checkpoint inhibitors, including expression of programmed death-ligand 1 (PD-L1) and major histocompatibility complex (MHC) I, microsatellite instability (MSI), mismatch repair (MMR) defect, tumor mutation burden (TMB), tertiary lymphoid structures (TLSs), and several transcriptional signatures, the sensitivity of these indicators remains to be further improved. Materials and methods: Here, we integrated T-cell spatial distribution and intratumor transcriptional signals in predicting the response to immune checkpoint therapy in MMR-deficient tumors including tumors of Lynch syndrome (LS). Results: In both cohorts, MMR-deficient tumors displayed personalized tumor immune signatures, including inflamed, immune excluded, and immune desert, which were not only individual-specific but also organ-specific. Furthermore, the immune desert tumor exhibited a more malignant phenotype characterized by low differentiation adenocarcinoma, larger tumor sizes, and higher metastasis rate. Moreover, the tumor immune signatures associated with distinct populations of infiltrating immune cells were comparable to TLSs and more sensitive than transcriptional signature gene expression profiles (GEPs) in immunotherapy prediction. Surprisingly, the tumor immune signatures might arise from the somatic mutations. Notably, patients with MMR deficiency had benefited from the typing of immune signatures and later immune checkpoint inhibition. Conclusion: Our findings suggest that compared to PD-L1 expression, MMR, TMB, and GEPs, characterization of the tumor immune signatures in MMR-deficient tumors improves the efficiency of predicting the responsiveness of immune checkpoint inhibition.

NT-proBNP Levels and Collateral Circulation Status in Patients with Acute Ischemic Stroke.

Methods: In this study, 326 hospitalized patients with acute anterior circulation ischemic stroke (AACIS) were included. A comparison of the clinical characteristics of those with and without AF was conducted. The Spearman rank correlation was used for the correlation analysis of plasma NT-proBNP level, regional leptomeningeal collateral (rLMC) score, and computed tomography perfusion (CTP) status in the AF and non-AF groups. An analysis of multivariate linear regression was used to determine how plasma NT-proBNP level, rLMC score, and CTP status influenced the score on the NIHSS. Results: There was a greater plasma NT-proBNP level in the AF group compared with the non-AF group, an increased CTP volume (including CTP ischemic volume, CTP infarct core volume, and CTP ischemic penumbra volume (P = 0.002)), higher NIHSS score on admission, and lower rLMC score (P < 0.001 for the remaining parameters). A negative correlation exists between plasma NT-proBNP level and rLMC score (r = -0.156, P = 0.022), but a positive correlation exists between plasma NT-proBNP level and both CTP ischemic volume and CTP infarct core volume (r = 0.148, P = 0.003) in the AF group, but not in the non-AF group. Multivariate linear regression analysis demonstrated that NT-proBNP, CTP ischemic penumbra volume, and rLMC score were associated with NIHSS score, and NT-proBNP was positively associated with NIHSS scores (95% confidence interval (CI), 0.000-0.002; P = 0.004) in the AF group, whatever in the unadjusted model or adjusted models, but not in the nonlarge artery atherosclerosis (LAA) group. Conclusion: In AACIS patients with AF, NT-proBNP level negatively correlated with collateral status, positively with CTP ischemic volume, and positively with NIHSS score.