Solanesol alleviates CFA-induced chronic inflammatory pain via inhibition of proinflammatory cytokines in spinal glial cells.

Solanesol, an aliphatic terpene alcohol predominantly found in solanaceous plants, has gained recognition for its anti-inflammatory, antibacterial, and neuroprotective properties. This study investigates the potential efficacy of solanesol in alleviating chronic inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into the left hind paw. Behavioral assessments revealed a significant reduction in mechanical and thermal hypersensitivity following solanesol administration, accompanied by a partial alleviation of concomitant anxiety-like behaviors. Mechanistically, Western blot analysis demonstrated a substantial decrease in the levels of TNF-α and IL-1ß after solanesol administration. Immunohistochemical staining further revealed a notable suppression of microglial and astrocytic activation induced by CFA injection. These findings collectively suggest that solanesol holds promise as a latent therapeutic agent for the treatment of chronic inflammatory pain.

Trophic transfer of dechloranes in marine food webs in Dalian Bay, China.

Dechloranes, including dechlorane 602 (Dec 602), dechlorane 603 (Dec 603), dechlorane 604 (Dec 604), dechlorane plus (DP, including syn- and anti-DP) and mirex, were determined in marine food web from Dalian Bay, Northeast China to investigate their occurrence andtrophic transfer. In all organisms, the detection rates were Dec 602 (99%) > mirex (95%) > Dec 603 (92%) > anti-DP (91%) > syn-DP (82%) > Dec 604 (9.6%). The concentrations were 0.92-16 ng/g lipid weight (lw) for mirex, 0.53-2.3 ng/g lw for syn-DP, 1.1-4.5 ng/g lw for anti-DP, 0.19-5.0 ng/g lw for Dec 602, 0.26-1.9 ng/g lw for Dec 603 and 0.020-0.33 ng/g lw for Dec 604. Significant positive relationships (p < 0.0001) were observed between lipid normalized concentrations and trophic levels for mirex (R2 = 0.80) and Dec602 (R2 = 0.82) in food webs, with the calculated TMFs values of 3.09 and 3.39, respectively, indicating the trophic magnification potential of these compounds. For syn-DP, anti-DP, Dec 603 and Dec 604, the similar significant relationships were not found, suggesting that these chemicals do not trophic magnification nor trophic dilution in the food web. With low log KOW values for mirex (7.01) and Dec 602 (8.05), these two compounds have the highest magnifications potentials, while the magnification potential of Dec 603, Dec 604 and DP dramatically decreased because of their extremely big log KOW values (higher than 10). The observed fractional abundance of anti-DP (fanti) ranged of 0.58-0.69, closing to the one in Chinese industrial products, indicating DP isomers had not undergone significant differences of physicochemical or biological process in the studied food web.

Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications.

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.

Quercetin promotes the proliferation, migration, and invasion of trophoblast cells by regulating the miR-149-3p/AKT1 axis.

Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR-8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit-8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR-8/SVneo cells, respectively. To assess the expression levels of miR-149-3p and AKT serine/threonine kinase 1 (AKT1), quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were performed. A dual-luciferase reporter assay was used to investigate the potential regulatory relationship between miR-149-3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E-cadherin. Mechanistically, QCT downregulated the expression of miR-149-3p and upregulated the expression of AKT1, and miR-149-3p directly targets AKT1, negatively regulating its expression. Overexpression of miR-149-3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR-8/SVneo cells through the miR-149-3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.

Bio-active metabolites from Chinese Medicinal Herbs for treatment of skin diseases.

Skin diseases have become serious issues to human health and affect one-third of the world's population according to the World Health Organisation (WHO). These consist of internal (endogenous) and external (exogenous) factors referring to genetics, hormones, and the body's immune system, as well as environmental situations, UV radiation, or environmental pollution respectively. Generally, Western Medicines (WMs) are usually treated with topical creams or strong medications for skin diseases that help superficially, and often do not treat the root cause. The relief may be instant and strong, sometimes these medicines have adverse reactions that are too strong to be able and sustained over a long period, especially steroid drug type. Chinese Medicinal Herbs (CMHs) are natural resources and relatively mild in the treatment of both manifestation and the root cause of disease. Nowadays, CMHs are attractive to many scientists, especially in studying their formulations for the treatment of skin diseases. METHODS: The methodology of this review was searched in nine electronic databases including WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without regard to language constraints. All eligible studies are analysed and summarised. RESULTS: Based on the literature findings, some extracts or active metabolites divided from CMHs, including Curcumin, Resveratrol, Liquorice, Dandelions, Cortex Moutan, and Calendula officinalis L., are effective for the treatment and prevention of skin diseases because of a wide range of pharmacological activities, e.g. anti-bacterial, anti-microbial, anti-virus, and anti-inflammation to enhance the body's immune system. It is also responsible for skin whitening to prevent pigmentation and premature ageing through several mechanisms, such as regulation or inhibition of nuclear factor kappa B (IκB/NF-κB) signalling pathways. CONCLUSION: This is possible to develop CMHs, such as Curcumin, Resveratrol, Liquorice, Dandelions, Cortex Moutan and Calendula officinalis L. The ratio of multiple CMH formulations and safety assessments on human skin diseases required studying to achieve better pharmacological activities. Nano formulations are the future investigation for CMHs to combat skin diseases.

Recent Development of Biodegradable Occlusion Devices for Intra-Atrial Shunts.

Atrial septal defect (ASD) is the third most common type of structural congenital heart defect. Patent foramen ovale (PFO) is an anatomical anomaly in up to 25% of the general population. With the innovation of occlusion devices and improvement of transcatheter techniques, percutaneous closure has become a first-line therapeutic alternative for treatment of ASD and PFO. During the past few decades, the development of biodegradable occlusion devices has become a promising direction for transcatheter closure of ASD/PFO due to their biodegradability and improved biocompatibility. The purpose of this review is to comprehensively summarize biodegradable ASD/PFO occlusion devices, regarding device design, materials, biodegradability, and evaluation of animal or clinical experiments (if available). The current challenges and the research direction for the development of biodegradable occluders for congenital heart defects are also discussed.

Influence of the examination position and distension medium on the rectal sensory test in patients with functional constipation.

PURPOSE: To evaluate the impact of two different parameters (body position and distension medium) on the rectal sensory test in patients with functional constipation and provide data support for the development of standardized operating procedures in clinical practice. METHODS: Based on a single-center process of the rectal sensory test, 39 patients with functional constipation were recruited for rectal sensory test under different body positions and distension mediums. RESULTS: Among the items of the Constipation Scoring System, the score of frequency of bowel movements showed a negative correlation with the first constant sensation volume (r = -0.323, P = 0.045). Conversely, the score of painful evacuation effort showed a positive correlation with the desire to defecate volume (r = 0.343, P = 0.033). There was a statistically significant difference in the first constant sensation volume (when the distension medium was gas) measured in different body positions (left lateral position, sitting position, squatting position), and the data measured in the squatting position were significantly higher than those in left lateral position (P < 0.05). In terms of research on distension medium, it was found that the first constant sensation volume measured in the squatting position (when the distension medium was water) was significantly lower than that of gas (P < 0.05). CONCLUSION: For patients with functional constipation, there are differences in the results of rectal sensory tests between body positions and distension mediums. When conducting multicenter studies, it is necessary to unify the standard operating procedure (SOP) for operational details to ensure consistency and reliability of the test results.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

Air-sea exchange of PAHs in the Taiwan Strait: Seasonal dynamics and regulation mechanisms revealed by machine learning approach.

In this study, to understand the seasonal dynamics of air-sea exchange and its regulation mechanisms, we investigated polycyclic aromatic hydrocarbons (PAHs) at the air-sea interface in the western Taiwan Strait in combination with measurements and machine learning (ML) predictions. For 3-ring PAHs and most of 4- to 6-ring, volatilization and deposition fluxes were observed, respectively. Seasonal variations in air-sea exchange flux suggest the influence of monsoon transitions. Results of interpretable ML approach (XGBoost) indicated that volatilization of 3-ring PAHs was significantly controlled by dissolved PAH concentrations (contributed 24.0 %), and the gaseous deposition of 4- to 6-ring PAHs was related to more contaminated air masses originating from North China during the northeast monsoon. Henry's law constant emerged as a secondary factor, influencing the intensity of air-sea exchange, particularly for low molecular weight PAHs. Among environmental parameters, notably high wind speed emerges as the primary factor and biological pump's depletion of PAHs in surface seawater amplifies the gaseous deposition process. The distinct dynamics of exchanges at the air-water interface for PAHs in the western TWS can be attributed to variations in primary emission intensities, biological activity, and the inconsistent pathways of long-range atmospheric transport, particularly within the context of the monsoon transition.

High-throughput screening of 222 pesticides in road environments in a megacity of northern China: A new approach to urban population exposure.

A large number of pesticides have been widely manufactured and applied, and are released into the environment with negative impact on human health. Pesticides are largely used in densely populated urban environments, in green zones, along roads and on private properties. In order to characterize the potential exposure related health effects of pesticide and their occurrence in the urban environment, 222 pesticides were screened and quantified in 228 road dust and 156 green-belt soil samples in autumn and spring from Harbin, a megacity in China, using GC-MS/MS base quantitative trace analysis. The results showed that a total of 33 pesticides were detected in road dust and green-belt soil, with the total concentrations of 650 and 236 ng/g (dry weight = dw), respectively. The concentrations of pesticides in road dust were significantly higher than that in green-belt soil. Pesticides in the environment were influenced by the seasons, with the highest concentrations of insecticides in autumn and the highest levels of herbicides in spring. In road dust, the concentrations of highways in autumn and spring (with the mean values of 94.1 and 68.2 ng/g dw) were much lower than that of the other road classes (arterial roads, sub-arterial roads and branch ways). Whereas in the green-belt soil, there was no significant difference in the concentration of pesticides between the different road classes. A first risk assessment was conducted to evaluate the potential adverse health effects of the pesticides, the results showed that the highest hazard index (HI) for a single pesticide in dust and soil was 0.12, the hazard index for children was higher than that for adults, with an overall hazard index of less than 1. Our results indicated that pesticide levels do not have a significant health impact on people.

Temperature dependence of the rain-gas and snow-gas partition coefficients for nearly a thousand chemicals.

Compared to the particle-gas partition coefficients (KPG), the rain-gas (KRG) and snow-gas (KSG) partition coefficients are also essential in studying the environmental behavior and fate of chemicals in the atmosphere. While the temperature dependence for the KPG have been extensively studied, the study for KRG and KSG are still lacking. Adsorption coefficients between water surface-air (KIA) and snow surface-air (KJA), as well as partition coefficients between water-air (KWA) and octanol-air (KOA) are vital in calculating KRG and KSG. These four basic adsorption and partition coefficients are also temperature-dependent, given by the well-known two-parameters Antoine equation logKXY = AXY + BXY/T, where KXY is the adsorption or partition coefficients, AXY and BXY are Antoine parameters (XY stand for IA, JA, WA, and OA), and T is the temperature in Kelvin. In this study, the parameters AXY and BXY are calculated for 943 chemicals, and logKXY can be estimated at any ambient temperature for these chemicals using these Antoine parameters. The results are evaluated by comparing these data with published experimental and modeled data, and the results show reasonable accuracy. Based on these coefficients, temperature-dependence of logKRG and logKSG is studied. It is found that both logKRG and logKSG are linearly related to 1/T, and Antoine parameters for logKRG and logKSG are also estimated. Distributions of the 943 chemicals in the atmospheric phases (gas, particle, and rain/snow), are illustrated in a Chemical Space Map. The findings reveal that, at environmental temperatures and precipitation days, the dominant state for the majority of chemicals is the gaseous phase. All the AXY and BXY values for logKSG, logKRG, and basic adsorption and partition coefficients, both modeled by this study and collected from published work, are systematically organized into an accessible dataset for public utilization.

Imidacloprid removal by modified graphitic biochar with Fe/Zn bimetallic oxides.

Coping with the critical challenge of imidacloprid (IMI) contamination in sewage treatment and farmland drainage purification, this study presents a pioneering development of an advanced modified graphitic white melon seed shells biochar (Fe/Zn@WBC). The Fe/Zn@WBC demonstrates a substantial enhancement in adsorption efficiency for IMI, achieving a remarkable removal rate of 87.69% within 30 min and a significantly higher initial adsorption rate parameter h = 4.176 mg g-1·min-1. This significant improvement outperforms WBC (12.22%, h = 0.115 mg g-1·min-1) and highlights the influence of optimized adsorption conditions at 900 °C and the graphitization degree resulting from Fe/Zn bimetallic oxide modification. Characterization analysis and batch sorption experiments including kinetics, isotherms, thermodynamics and pH factors illustrate that chemical adsorption is the main type of adsorption mechanism responsible for this superior ability to remove IMI through pore filling, hydrogen bonding, hydrophobic interaction, electrostatics interaction, π-π interactions as well as complexation processes. Furthermore, we demonstrate exceptional stability of Fe/Zn@WBC across a broad pH range (pH = 3-11), co-existing ions presence along with humic acid under various real water conditions while maintaining high removal efficiency. This study presents an advanced biochar adsorbent, Fe/Zn@WBC, with efficient adsorption capacity and easy preparation. Through three regeneration cycles via pyrolysis method, it demonstrates excellent pyrolysis regeneration capabilities with an average removal efficiency of 92.02%. The magnetic properties enable rapid separation facilitated by magnetic analysis. By elucidating the efficacy and mechanistic foundations of Fe/Zn@WBC, this research significantly contributes to the field of environmental remediation by providing a scalable solution for IMI removal and enhancing scientific understanding of bimetallic oxides-hydrophilic organic pollutant interactions.

METTL5 promotes cell proliferation, invasion, and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer.

BACKGROUND: N6-methyladenosine (m6A) modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors. However, despite its significance, the comprehensive investigation of METTL5, a key m6A methyltransferase, in colorectal cancer (CRC) remains limited. AIM: To investigate the role of METTL5 in CRC. METHODS: We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines. To elucidate the downstream targets of METTL5, we performed RNA-sequencing analysis coupled with correlation analysis, leading us to identify Toll-like receptor 8 (TLR8) as a potential downstream target. In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays, scratch assays, as well as assays measuring cell migration and invasion. RESULTS: Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues, which correlated significantly with an unfavorable prognosis. In vitro experiments unequivocally demonstrated the oncogenic role of METTL5, as evidenced by its promotion of CRC cell proliferation, invasion, and migration. Notably, we identified TLR8 as a downstream target of METTL5, and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation, invasion, and tumor growth. CONCLUSION: The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis, thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.

Occurrence, seasonal variations, and fate of household and personal care chemicals in a wastewater treatment plant with Bacillus bioreactor process.

Household and personal care chemicals (HPCCs) constitute a significant component of everyday products, with their global usage on the rise. HPCCs are eventually discharged into municipal wastewater treatment plants (WWTPs). However, the behaviors of HPCCs inside the Bacillus Bioreactor (BBR) process, including their prevalence, fate, and elimination mechanisms, remain underexplored. Addressing this gap, our study delves into samples collected from a BBR process at a significant WWTP in the northeast of China. Our results spotlight the dominance of linear alkylbenzene sulfonates (LASs) in the influent with concentrations ranging between 238 and 789 µg/L, much higher than the other HPCC concentrations, and remained dominant in the subsequent treatment units. After treatment using the BBR process, the concentrations of HPCCs in the effluent were diminished. Examination of different treatment units underscores the grit chamber removed over 60% of higher-concentration HPCCs, while the performance of the (RBC) tank needs to be improved. Except for the ultraviolet radiation (UV)-filters, seasonal variations exert minimal impact on the concentrations and removal efficiencies of other HPCCs in the BBR process. According to the mass balance analysis, the important mechanisms for HPCC removal were biodegradation and sludge adsorption. Also, the octocrylene (OCT) concerns raised by the environmental risk assessment of the HPCCs residuals in the final effluent, indicate a moderate risk to the surrounding aquatic environment (0.1 < RQ < 1), whereas other HPCCs have a lower risk level (RQ < 0.1). Overall, the research offers new perspectives on the fate and elimination mechanisms of HPCCs throughout the BBR process.

Recent advances and prospects of neonicotinoid insecticides removal from aquatic environments using biochar: Adsorption and degradation mechanisms.

In recent years, neonicotinoid insecticides (NNIs), representing a new era of pest control, have increasingly replaced traditional classes such as organophosphorus compounds, carbamates, and pyrethroids due to their precise targeting and broad-spectrum efficacy. However, the high water solubility of NNIs has led to their pervasion in aquatic ecosystems, raising concerns about potential risks to non-target organisms and human health. Therefore, there is an urgent need for research on remediating NNI contamination in aquatic environments. This study demonstrates that biochar, characterized by its extensive surface area, intricate pore structure, and high degree of aromaticity holds significant promise for removing NNIs from water. The highest reported adsorption capacity of biochar for NNIs stands at 738.0 mg·g-1 with degradation efficiencies reaching up to 100.0 %. This review unveils that the interaction mechanisms between biochar and NNIs primarily involve π-π interactions, electrostatic interactions, pore filling, and hydrogen bonding. Additionally, biochar facilitates various degradation pathways including Fenton reactions, photocatalytic, persulfate oxidations, and biodegradation predominantly through radical (such as SO4-, OH, and O2-) as well as non-radical (such as 1O2 and electrons transfer) processes. This study emphasizes the dynamics of interaction between biochar surfaces and NNIs during adsorption and degradation aiming to elucidate mechanistic pathways involved as well as assess the overall efficacy of biochar in NNI removal. By comparing the identification of degradation products and degradation pathways, the necessity of advanced oxidation process is confirmed. This review highlights the significance of harnessing biochar's potential for mitigating NNI pollution through future application-oriented research and development endeavors, while simultaneously ensuring environmental integrity and promoting sustainable practices.

Circ-0075305 hinders gastric cancer stem cells by indirectly disrupting TCF4-ß-catenin complex and downregulation of SOX9.

CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a ß-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4-ß-catenin transcription complex through competitive to ß-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/ß-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing ß-catenin signaling may serve as a potential therapeutic candidate.

Impact of chemotherapy delay on long-term prognosis of laparoscopic radical surgery for locally advanced gastric cancer: a pooled analysis of four randomized controlled trials.

BACKGROUND: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II-III locally AGC and explore the associated risk factors. METHODS: Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established. RESULTS: In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II-III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets. CONCLUSION: Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II-III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum: Two case reports.

BACKGROUND: SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting (SWI/SNF) complexes and plays an essential role in oncogenesis. SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis. There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies. Programmed death 1 (PD-1) antibodies, known as immune checkpoint inhibitor antibodies, potentially play a role in treating gastrointestinal tract malignancies. CASE SUMMARY: We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum. For both patients, SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein, while TP53 gene mutations were observed via next-generation sequencing. Both patients were administered chemotherapy in combination with an anti-PD-1 antibody. The two patients exhibited completely different responses to treatment and had different prognoses. Case 1 experienced rapid progression after PD-1 infusion and chemotherapy, case 2 experienced a remarkable response after treatment, and the progression-free survival was more than 6 months. CONCLUSION: This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum. PD-1 combined with chemotherapy showed a certain efficacy in select patients, providing options for treating these highly malignant tumors. Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

Seasonal patterns, fate and ecological risk assessment of pharmaceutical compounds in a wastewater treatment plant with Bacillus bio-reactor treatment.

Pharmaceutical compounds (PhCs) pose a growing concern with potential environmental impacts, commonly introduced into the environment via wastewater treatment plants (WWTPs). The occurrence, removal, and season variations of 60 different classes of PhCs were investigated in the baffled bioreactor (BBR) wastewater treatment process during summer and winter. The concentrations of 60 PhCs were 3400 ± 1600 ng/L in the influent, 2700 ± 930 ng/L in the effluent, and 2400 ± 120 ng/g dw in sludge. Valsartan (Val, 1800 ng/L) was the main contaminant found in the influent, declining to 520 ng/L in the effluent. The grit chamber and BBR tank were substantially conducive to the removal of VAL. Nonetheless, the BBR process showcased variable removal efficiencies across different PhC classes. Sulfadimidine had the highest removal efficiency of 87 ± 17% in the final effluent (water plus solid phase). Contrasting seasonal patterns were observed among PhC classes within BBR process units. The concentrations of many PhCs were higher in summer than in winter, while some macrolide antibiotics exhibited opposing seasonal fluctuations. A thorough mass balance analysis revealed quinolone and sulfonamide antibiotics were primarily eliminated through degradation and transformation in the BBR process. Conversely, 40.2 g/d of macrolide antibiotics was released to the natural aquatic environment via effluent discharge. Gastric acid and anticoagulants, as well as cardiovascular PhCs, primarily experienced removal through sludge adsorption. This study provides valuable insights into the intricate dynamics of PhCs in wastewater treatment, emphasizing the need for tailored strategies to effectively mitigate their release and potential environmental risks.

Circadian changes of autonomic function in patients with zoster-associated pain: A heart rate variability analysis.

OBJECTIVE: To investigate the circadian changes of the autonomic function in patients with zoster-associated pain (ZAP). METHODS: A total of 37 patients with ZAP from April 2022 to October 2022 were enrolled as the observation group, and 37 normal volunteers at the same time were selected as the control group. All participants were required to wear a 24-h Holter, which was used to compare the heart rate variability (HRV) between the two groups. HRV analysis involved time- and frequency-domain parameters. RESULTS: There was no statistically significant difference in general information between two groups. Patients with ZAP had an increased mean heart rate and decreased the standard deviation of normal-to-normal (SDNN) R-R interval, the root mean square of the differences (RMSSD) in successive RR interval, low frequency (LF), and high frequency (HF) compared with control groups in all periods (p < .05). The ratio of LF/HF between two groups had no significant difference (p = .245). SDNN had no significant difference between day and night in the control group (p > .05), whereas SDNN of ZAP patients in night period was reduced than that in day period (p < .001). The level of RMSSD during the day was lower than those at night in the control group (p < .05), whereas no significant difference of RMSSD between two periods was observed in patients with ZAP (p > .05). CONCLUSION: The results of this study indicated that ZAP contributes to the decline of autonomic nervous system (ANS) function, especially parasympathetic components. The patients with ZAP lost parasympathetic advantage and had a worse ANS during the night.