Application of Monte Carlo simulation to optimise the dosage regimen of meropenem in patients with augmented renal clearance for Pseudomonas aeruginosa infection.

Objective: To optimise the dosing regimen of meropenem for treating Pseudomonas aeruginosa (PA) infections in critically ill patients with augmented renal clearance (ARC) using pharmacokinetic/pharmacodynamic (PK/PD) principles and Monte Carlo simulation (MCS). Methods: This research involves an MCS based on PK data from patients with ARC and a minimum inhibitory concentration (MIC) distribution of PA. This study simplifies the methods section, focusing on the critical aspects of simulation and target values for effective treatment. Results: The study highlights key findings and emphasises that tailored dosing based on bacterial MIC values is essential for patients with ARC. It also notes that empirical treatment in patients with ARC should consider the MIC distribution, with 2 g every (q) 6 h administered to achieve the PK/PD target, while 3 g q 6 h is effective in inhibiting resistance. Conclusion: Tailored dosing based on bacterial MIC values is crucial for patients with ARC. Prolonged infusion time alone does not enhance efficacy. Empirical treatment in patients with ARC should consider MIC distribution; a dosage of 2 g q 6 h achieves the PK/PD target, while 3 g q 6 h (≥12 g daily) inhibits resistance.

Mechanisms of stationary voltage fluctuation in the neuromuscular junction endplate and corresponding denoising paradigms.

The neuromuscular junction (NMJ) has an elaborate anatomy to ensure agile and accurate signal transmission. Based on our formerly obtained expressions of the thermal and conductance induced voltage fluctuations, in this paper, the mechanisms underlying the conductance-induced voltage fluctuation are characterized from two aspects: the scaling laws with respect to either of the two system-size factors, the number of receptors or the membrane area; and the "seesaw effect" with respect to the intensive parameter, the concentration of acetylcholine. According to these mechanisms, several aspects of the NMJ anatomy are explained from a denoising perspective. Finally, the power spectra of the two types of voltage fluctuations are characterized by their specific scaling laws, based on which we explain why the endplate noise has the low-frequency property that is described by the term "seashell sound".

The effect of cold plasma on starch: Structure and performance.

The inherent side effects of the physico-chemical properties of native starches often severely limit their use in food and non-food industries. Plasma is a non-thermal technology that allows rapid improvement of functional properties. This review provides a comprehensive summary of the sources and mechanisms of action of cold plasma and assesses its effects on starch morphology, crystal structure, molecular chain structure and physicochemical properties. The complex relationship between structure and function of plasma-treated starch is also explored. Potential applications of plasma-modified starch are also discussed in detail. The outcome of the modification process is influenced by factors such as starch type and concentration, plasma source, intensity and duration. The properties of starch can be effectively optimised using plasma technology. Plasma-based technologies therefore have the potential to modify starch to create a range of functionalities to meet the growing market demand for clean label ingredients.

Effect of dielectric barrier discharge (DBD) plasma treatment on physicochemical and 3D printing properties of wheat starch.

In recent years, the focus has shifted towards carbohydrate-based hydrogels and their eco-friendly preparation methods. This study involved an investigation into the treatment of wheat starch using dielectric barrier discharge (DBD) plasma technology over varying time gradients (0, 2, 5, 10, 15, and 20 min). The objective was to systematically examine the impact of different treatment durations on the physicochemical properties of wheat starch and the suitability of its gels for 3D printing. Morphology of wheat starch remained intact after DBD treatment. However, it led to a reduction in the amylose content, molecular weight, and crystallinity. This subsequently resulted in a decrease in the pasting temperature and viscosity. Moreover, the gels of the DBD-treated starch exhibited superior 3D printing performance. After a 2-min DBD treatment, the 3D printed samples of the wheat starch gel showed no significant improvements, as broken bars were evident on the surface of the 3D printed graphic, whereas DBD-20 showed better printing accuracy and surface structure, compared to the original starch without slumping. These results suggested that DBD technology holds potential for developing new starch-based gels with impressive 3D printing properties.

Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer.

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

Effect of 3D printing and traditional molding on phenolic compounds and antioxidant activity in steamed bread.

The production process of fermented black wheat steamed bread is closely related to the overall quality and nutritional content. In this study, we investigated the accuracy, product texture profile and antioxidant activity of fermented black wheat steamed bread samples produced by piston and spiral three-dimensional (3D) printers. The steaming process generally increased the total phenolic content and flavonoid content of the samples. The spiral 3D printer obtained samples with higher accuracy, total phenolic content up to 1960.43 Mg GAE/kg, and higher cellular antioxidant activity (CAA) content. The samples printed by the piston 3D printer showed higher total flavonoid content (575.75 Mg QE/kg), 2, 2'-azobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) values and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) values. This study shows that antioxidant-rich health foods can be prepared using 3D printed black wheat flour. The choice of 3D printing method affects the overall quality and nutritional content of the final product.

Association between life's essential 8 and periodontitis: a population-based study.

BACKGROUND: The American Heart Association has developed a novel cardiovascular health indicator called Life's Essential 8 (LE8). However, no one has reported using LE8 to assess periodontitis. This study aimed to investigate the association between LE8 and periodontitis in American adults. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014 were used for this investigation. LE8 was the independent variable, and it is divided into three grades: high, moderate, and low. Periodontitis was the dependent variable, and the classification of periodontitis was based on the criteria of Eke in 2012. Multivariable logistic regression models were used to explore the relationship between LE8 and periodontitis. RESULTS: A total of 9,039 participants with an average age of 52.16 ± 14.21 years were enrolled in this study, of whom 48.29% were male and 51.71% were female. The mean and standard deviation of LE8 was 66.29 ± 14.57, and the prevalence of periodontitis was 50.48% overall. The LE8 score and periodontitis in the fully adjusted logistic regression model showed a negative correlation (OR = 0.98; 95% CI, 0.98-0.99, p < 0.001). This result persisted when Life's Essential 8 was categorized into low, moderate, and high groups. Compared with those in the lowest group, those in the highest LE8 group had a 47% decreased risk of periodontitis (OR = 0.53; 95% CI, 0.46-0.66, P < 0.001). CONCLUSIONS: This cross-sectional investigation revealed a negative relationship between the LE8 score and the likelihood of periodontitis.

Revealing varying relationships between wastewater mercury emissions and economic growth in Chinese cities.

Mercury emission from industrial wastewater has a great impact on the aquatic environment but is not well studied. Inventory analysis, decoupling and decomposition methods have been conducted based on the China Pollution Source Census dataset, which combines industry removal efficiencies to calculate mercury emissions from industrial wastewater in 340 cities in China during 2000-2010. The results show that over these 11 years, total mercury emissions and per capita mercury emissions increased by approximately 5 times, while the emission intensity increased by only about 3%. From 2000 to 2010, only 0.59% of cities showed strong decoupling between economic growth and mercury emissions, and 37.65% of cities showed weak decoupling, whereas 38.82% of cities showed negative decoupling. We attribute the decoupling of economic development and emissions in individual cities to several socioeconomic factors and find that a decline in emission intensity is the main driver. The Gini coefficient indicates a significant imbalance between cities' emissions, but this situation improved during 2000-2010. The objective of this article is to provide a historical perspective on the situation of mercury emissions from wastewater in China, thereby contributing' to the broader understanding of industrial pollution.

Using voice recognition to measure trust during interactions with automated vehicles.

Trust in an automated vehicle system (AVs) can impact the experience and safety of drivers and passengers. This work investigates the effects of speech to measure drivers' trust in the AVs. Seventy-five participants were randomly assigned to high-trust (the AVs with 100% correctness, 0 crash, and 4 system messages with visual-auditory TORs) and low-trust group (the AVs with a correctness of 60%, a crash rate of 40%, 2 system messages with visual-only TORs). Voice interaction tasks were used to collect speech information during the driving process. The results revealed that our settings successfully induced trust and distrust states. The corresponding extracted speech feature data of the two trust groups were used for back-propagation neural network training and evaluated for its ability to accurately predict the trust classification. The highest classification accuracy of trust was 90.80%. This study proposes a method for accurately measuring trust in automated vehicles using voice recognition.

Development and validation of a scoring system to predict esophagogastroduodenoscopy necessity.

OBJECTIVE: This study aimed to develop and validate a scoring system for predicting the need for esophagogastroduodenoscopy (EGD) in clinical practice to enhance accuracy and reduce misapplications. METHODS: From February 2021 to April 2022, outpatients scheduled for EGD at the Department of Gastroenterology in our hospital were recruited. Patients completed the system evaluation by providing clinical symptoms, relevant medical history, and endoscopic findings. Patients were randomly divided into the training and validation cohorts (at 2:1 ratio). The optimal algorithm was selected from five alternatives including a parallel test. Six physicians participated in a human-computer comparative validation. Sensitivity and negative likelihood ratio (-LR) were used as the primary indicators. RESULTS: Altogether 865 patients were enrolled, with 578 in the training cohort and 287 in the validation cohort. The scoring system comprised 21 variables, including age, 13 typical clinical symptoms, and seven medical history variables. The parallel test was selected as the final algorithm. Positive EGD findings were reported in 54.5% of the training cohort and 62.7% of the validation cohort. The scoring system demonstrated a sensitivity of 79.0% in the training cohort and 83.9% in the validation cohort, with -LR being 0.627 and 0.615, respectively. Compared to physicians, the scoring system exhibited higher sensitivity (84.0% vs 68.7%, P = 0.02) and a lower -LR (1.11 vs 2.41, P = 0.439). CONCLUSIONS: We developed a scoring system to predict the necessity of EGD using a parallel test algorithm, which was user-friendly and effective, as evidenced by single-center validation.

Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention: A Secondary Analysis of the OPT-PEACE Randomized Clinical Trial.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

[Short-term nitrogen deposition changes chemical composition of litter and soil organic matter in a Moso bamboo forest]. / 短期氮沉降改变毛竹林凋落物和土壤有机质化学组成.

To investigate the effects of short-term nitrogen (N) deposition on organic matter composition of litter and soil in Moso bamboo (Phyllostachys edulis) forests, we established a N-addition treatments (50 kg N·hm-2·a-1) to simulate the ambient and N deposition in a subtropical Moso bamboo forest from July 2020 to January 2022. We analyzed the organic matter composition of Moso bamboo leaf/root litter and soil by using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) technique. The results showed that short-term N deposition significantly increased the relative content of soil phenols by 50.9%, while significantly decreased fatty acids by 26.3%. The rela-tive content of alkanes & alkenes and lignin in leaf litter was significantly increased by 51.9% and 33.5%, respectively, while that of phenols and polysaccharides significantly decreased by 52.2% and 56.3%. In root litter, eleva-ted N significantly decreased the relative content of polycyclic aromatic hydrocarbons by 16.6%. Moreover, the relative content of fatty acids in soil organic matter was significantly positively correlated with the relative content of poly-saccharides in leaf litter. The relative content of phenols in soil organic matter was significantly positively correlated with the relative content of lignin, and negatively correlated with the relative content of polysaccharides in leaf litter. Our results demonstrated that short-term N deposition did not change the concentration of total organic carbon, total nitrogen, and C/N of the soil, leaf litter, and root litter, but significantly altered the chemical composition of organic matter. In addition, the changes in chemical composition of organic matter in soil under short-term N deposition were affected by the composition of organic matter in leaf litter.

ILC1-derived IFN-γ regulates macrophage activation in colon cancer.

BACKGROUND: Tumor-associated macrophages (TAMs) are an important subset of innate immune cells in the tumor microenvironment, and they are pivotal regulators of tumor-promoting inflammation and tumor progression. Evidence has proven that TAM numbers are substantially increased in cancers, and most of these TAMs are polarized toward the alternatively activated M2 phenotype; Thus, these TAMs strongly promote the progression of cancer diseases. Type 1 innate lymphocytes (ILC1s) are present in high numbers in intestinal tissues and are characterized by the expression of the transcription factor T-bet and the secretion of interferon (IFN)-γ, which can promote macrophages to polarize toward the classically activated antitumor M1 phenotype. However, the relationship between these two cell subsets in colon cancer remains unclear. METHODS: Flow cytometry was used to determine the percentages of M1-like macrophages, M2-like macrophages and ILC1s in colon cancer tissues and paracancerous healthy colon tissues in the AOM/DSS-induced mouse model of colon cancer. Furthermore, ILC1s were isolated and bone marrow-derived macrophages were generated to analyze the crosstalk that occurred between these cells when cocultured in vitro. Moreover, ILC1s were adoptively transferred or inhibited in vivo to explore the effects of ILC1s on tumor-infiltrating macrophages and tumor growth. RESULTS: We found that the percentages of M1-like macrophages and ILC1s were decreased in colon cancer tissues, and these populations were positively correlated. ILC1s promoted the polarization of macrophages toward the classically activated M1-like phenotype in vitro, and this effect could be blocked by an anti-IFN-γ antibody. The in vivo results showed that the administration of the Group 1 innate lymphocyte-blocking anti-NK1.1 antibody decreased the number of M1-like macrophages in the tumor tissues of MC38 tumor-bearing mice and promoted tumor growth, and adoptive transfer of ILC1s inhibited tumors and increased the percentage of M1-like macrophages in MC38 tumor-bearing mice. CONCLUSIONS: Our studies preliminarily prove for the first time that ILC1s promote the activation of M1-like macrophages by secreting IFN-γ and inhibit the progression of colon cancer, which may provide insight into immunotherapeutic approaches for colon cancer.

The effect of early oral nutritional supplements on improving nutritional outcomes and radiation-induced oral mucositis for nasopharyngeal carcinoma patients undergoing concurrent chemoradiotherapy.

BACKGROUND: To explore the value of early oral nutritional supplements (ONS) in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT). METHODS: Patients with newly diagnosed II-IVA stage NPC were analyzed and divided into Early and Routine ONS groups according to whether they received early ONS at the beginning of CCRT. Changes in nutritional indicators, incidence of treatment-related toxicity, radiation interruption, and completion of CCRT were compared. RESULTS: In total, 161 patients with NPC were analyzed, including 72 in the Early ONS group and 89 in the Routine ONS group. Multivariate analysis showed that early ONS was an independent protective factor for concurrent chemotherapy ≥2 cycles, and a protective factor against ≥grade 3 radiation-induced oral mucositis (RIOM) and weight loss >5%. In stage III-IVA patients, early ONS was beneficial in decreasing the risk of severe malnutrition. CONCLUSIONS: Early ONS can improve nutritional outcomes, reduce RIOM, and enhance treatment adherence.

Emerging Hypervirulent Marek's Disease Virus Variants Significantly Overcome Protection Conferred by Commercial Vaccines.

As one of the most important avian immunosuppressive and neoplastic diseases, Marek's disease (MD), caused by oncogenic Marek's disease virus (MDV), has caused huge economic losses worldwide over the past five decades. In recent years, MD outbreaks have occurred frequently in MD-vaccinated chicken flocks, but the key pathogenic determinants and influencing factors remain unclear. Herein, we analyzed the pathogenicity of seven newly isolated MDV strains from tumor-bearing chickens in China and found that all of them were pathogenic to chicken hosts, among which four MDV isolates, SDCW01, HNXZ05, HNSQ05 and HNSQ01, were considered to be hypervirulent MDV (HV-MDV) strains. At 73 days of the virus infection experiment, the cumulative incidences of MD were 100%, 93.3%, 90% and 100%, with mortalities of 83.3%, 73.3%, 60% and 86.7%, respectively, for the four viruses. The gross occurrences of tumors were 50%, 33.3%, 30% and 63.3%, respectively, accompanied by significant hepatosplenomegaly and serious atrophy of the immune organs. Furthermore, the immune protection effects of four commercial MD vaccines against SDCW01, CVI988, HVT, CVI988+HVT, and 814 were explored. Unexpectedly, during the 67 days of post-virus challenge, the protection indices (PIs) of these four MD vaccines were only 46.2%, 38.5%, 50%, and 28%, respectively, and the birds that received the monovalent CVI988 or HVT still developed tumors with cumulative incidences of 7.7% and 11.5%, respectively. To our knowledge, this is the first demonstration of the simultaneous comparison of the immune protection efficacy of multiple commercial MD vaccines with different vaccine strains. Our study revealed that the HV-MDV variants circulating in China could significantly break through the immune protection of the classical MD vaccines currently widely used. For future work, there is an urgent need to develop novel, more effective MD vaccines for tackling the new challenge of emerging HV-MDV strains or variants for the sustainable control of MD.

Tuina therapy promotes behavioral improvement and brain plasticity in rats with peripheral nerve injury and repair.

INTRODUCTION: Tuina is currently one of the popular complementary and alternative methods of rehabilitation therapy. Tuina can improve patients' pain and mobility function. However, the underlying physiological mechanism remains largely unknown, which might limit its further popularization in clinical practice. The aim of this study is to explore the short-term and long-term changes in brain functional activity following Tuina intervention for peripheral nerve injury repair. METHODS: A total of 16 rats were equally divided into the intervention group and the control group. Rats in the intervention group received Tuina therapy applying on the gastrocnemius muscle of the right side for 4 months following sciatic nerve transection and immediate repair, while the control group received nerve transection and repair only. The block-design functional magnetic resonance imaging scan was applied in both groups at 1 and 4 months after the surgery. During the scan, both the injured and intact hindpaw was electrically stimulated according to a "boxcar" paradigm. RESULTS: When stimulating the intact hindpaw, the intervention group exhibited significantly lower activation in the somatosensory area, limbic/paralimbic areas, pain-regulation areas, and basal ganglia compared to the control group, with only the prefrontal area showing higher activation. After 4 months of sciatic nerve injury, the control group exhibited decreased motor cortex activity compared to the activity observed at 1 month, and the intervention group demonstrated stronger bilateral motor cortex activity compared to the control group. CONCLUSION: Tuina therapy on the gastrocnemius muscle of rats with sciatic nerve injury can effectively alleviate pain and maintain the motor function of the affected limb. In addition, Tuina therapy reduced the activation level of pain-related brain regions and inhibited the decreased activity of the motor cortex caused by nerve injury, reflecting the impact of peripheral stimulation on brain plasticity.

Effectiveness of Acupuncture for Prophylactic Treatment of Migraine: A Systematic Review and Bayesian Network Meta-Analysis.

It is aimed to evaluate the effectiveness and provide evidence-based medical support for acupuncture as a prophylactic treatment for migraines. Randomized controlled trials (RCTs) from inception to April 2022 are included in 14 databases. Pairwise meta-analysis is conducted using STATA software V14.0, while Windows Bayesian Inference Using Gibbs Sampling (WinBUGS V.1.4.3) is applied to generate Bayesian Network Meta-analysis (NMA) using Markov chain Monte Carlo algorithm. Forty RCTs are included, with 4405 participants. The effectiveness of six acupuncture techniques, three types of prophylactic drugs, and psychotherapy are compared and ranked. Acupuncture outperformed prophylactic drugs in terms of diminishing visual analog scale (VAS) score, migraine attack frequency, and days during the treatment and at the 12-week follow-up. At the 12-week follow-up, the effectiveness of various interventions is ranked as follows: manual acupuncture (MA) > electroacupuncture (EA) > calcium antagonists (CA) in reducing VAS score; MA > EA > CA in reducing migraine attack frequency; MA > EA > ß-receptor blocker and CA in reducing headache attack days. Acupuncture is a promising treatment for migraine prevention. The best option of acupuncture for improving various migraine outcomes has changed over time. However, the quality of included trials and NMA inconsistency limited the credibility of the conclusion.

Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer.

The status of human epidermal growth factor receptor 2 (HER2) for the prognosis in colorectal cancer (CRC) is controversial, and the characteristics of the somatic mutation spectrum, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein are unknown in HER2-amplified colorectal cancer (HACC). In order to explore these characteristics along with their correlation with clinicopathological factors and prognosis in HACC. Samples of 812 CRC patients was collected. After immunohistochemistry (IHC), 59 of 812 were found to be HER2-positive, then 26 of 59 samples were further determined to be HER2 amplification by fluorescence in situ hybridization (FISH). Somatic mutation profiling of HACC was analysed using whole exome sequencing (WES). Multiplex fluorescence immunohistochemistry (mIHC) was used for tumor-infiltrating leukocytes and tertiary lymphoid structures (TLSs), while PD-L1 protein was detected by IHC. Our results indicate that the detection rates of HER2 positivity by IHC and FISH were 7.3% and 3.2% respectively, and HER2 amplification is correlated with distant tumour metastasis. The somatic mutation profiling revealed no differences between HACC and HER2-negative CRC. However, TP 53 strongly correlated with poor prognosis in HACC. Furthermore, tumor-infiltrating T cells and TLSs in the tumor immune microenvironment, as well as PD-L1 expression, were higher in HACC than in HER2-negative controls. However, none of them were associated with the prognosis of HACC. In all, HER2 amplification is correlated with distant metastasis and TP53 gene mutation may be a potential protective mechanism of HACC.