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Currently, immune checkpoint inhibitors (ICIs) have changed the treatment paradigm for many malignant tumors. As the most common digestive tract malignancy, colorectal cancer (CRC) shows a good response to ICIs only in a small subset of patients with MSI-H/dMMR CRC. In contrast, patients with MSS/pMMR CRC show minimal response to ICIs. The results of the REGONIVO study suggest that targeting the tumor microenvironment (TME) to improve immunotherapy outcomes in MSS/pMMR CRC patients is a feasible strategy. Therefore, this article focuses on exploring the feasibility of targeting the TME to enhance immunotherapy outcomes in CRC, collecting recent basic research on targeting the TME to enhance immunotherapy outcomes in CRC and analyzing ongoing clinical trials to provide a theoretical basis and future research directions for improving immunotherapy outcomes in MSS/pMMR CRC.

IntroductionLanguage delay cannot be ignored, and there is an urgent need to determine therapies that elicit better results in a short period. However, whether transcranial direct current stimulation (tDCS) alone or in combination with other therapies can promote recovery of language and cognitive function in children with language delay remains unknown. This study aims to explore the effects of tDCS combined with language-cognitive training and home-based rehabilitation on language and cognitive ability in children with language delay.MethodsChildren with language delay who visited the Department of rehabilitation medicine or the pediatric outpatient clinic of the First People’s Hospital of Foshan from January 2019 to December 2021, totaling 190 in number, were included and randomly divided into 4 groups, i.e., the family guidance group, the tDCS group, the language-cognitive training group, and the comprehensive training group. The family guidance group (47 cases) received home training. The tDCS group (46 cases) received home training and tDCS treatment. The language- cognitive training group (49 cases) adopted home training and language-cognitive training. The comprehensive training group (48 cases) took home training, language-cognitive training, and tDCS treatment. All groups received training 5 times a week for 4 weeks. The Sign-significant relations (S-S) test was applied to evaluate the language comprehension, language expression, basic learning ability, and attitude of communication of the children.ResultsThe language-cognitive training group and the comprehensive training group showed improvement after treatment (p < 0.05) regarding basic learning ability. The communication attitude of the four groups improved after intervention (p < 0.05). Particularly, the comprehensive training group had maximum improvement after intervention. No serious adverse reactions such as epilepsy, headache, and behavioral abnormalities were found.ConclusiontDCS combined with language-cognitive training and home training can improve language and cognitive ability in children with language delay.

AimTo investigate the efficacy and safety of high-calorie formula vs. Chinese daily food on the nutritional status and motor function of undernourished children with cerebral palsy (CP).MethodsIn this prospective, assessor-blind, and randomized controlled trial, we recruited children (1–10 years) with CP and undernutrition based on the WHO and the American Society for Parenteral and Enteral Nutrition criteria from the National Children's Medical Center. Participants were randomly allocated (1:1) to a high-calorie formula group or a Chinese daily food diet group (control group) for 6 months. Indirect calorimetry was used to estimate energy requirements. We compared the nutritional status and gross motor function of participants in both groups based on weight, height, z-scores (weight-for-age, height-for-age, weight-for-height, and BMI-for-age), and the Gross Motor Function Measure (GMFM), respectively, at baseline, 3-, and 6-months follow-up. In addition, the effective rate of nutritional intervention, and adverse events were simultaneously assessed.ResultsFrom July 2020 to December 2021, a total of 119 participants were enrolled and randomized, and 110 participants completed the study (with 54 children in the high-calorie formula group and 56 children in the control group). After 6 months of treatment, the weight, height, z-scores (weight-for-height, weight-for-age, and BMI-for-age), and GMFM of both groups were significantly improved (p < 0.05). There were significant differences in changes in weight, weight-for-age z-scores, and GMFM between the two groups (p < 0.05). During the study period, 16 children experienced at least one mild adverse event [9 (16.7%) in the formula group and 7 (12.5%) in the control group].ConclusionNutritional intervention with a high-calorie formula may be an effective and safe option in children with CP for improving undernutrition and gross motor dysfunction.Clinical trial registrationwww.chictr.org.cn, identifier: ChiCTR2000033878.

Constraint-induced movement therapy (CIMT) combined with repetitive transcranial magnetic stimulation (rTMS) have shown great potential in improving function in schoolchildren with unilateral cerebral palsy attributed to perinatal stroke. However, the prospect of application in preschool children with unilateral cerebral palsy (UCP) attributed to various brain disorders remains unclear. In this prospective, assessor-blinded, randomized controlled study, 40 preschool children with UCP (aged 2.5–6 years) were randomized to receive 10 days of CIMT combined with active or sham rTMS. Assessments were performed at baseline, 2 weeks, and 6 months post-intervention to investigate upper limb extremity, social life ability, and perceived changes by parents and motor-evoked potentials. Overall, 35 participants completed the trial. The CIMT plus active stimulation group had greater gains in the affected hand function (range of motion, accuracy, and fluency) than the CIMT plus sham stimulation group (P < 0.05), but there was no significant difference in muscular tone, social life ability, and perceived changes by parents between the two groups (P > 0.05). In addition, there was no significant difference in hand function between children with and without motor-evoked potential (P > 0.05). No participants reported severe adverse events during the study session. In short, the treatment of CIMT combined with rTMS is safe and feasible for preschool children with UCP attributed to various brain disorders. Randomized controlled studies with large samples and long-term effects are warranted.