Preventive and therapeutic effects of a super-multivalent sialylated filamentous bacteriophage against the influenza virus.

The resurgence of influenza viruses as a significant global threat emphasizes the urgent need for innovative antiviral strategies beyond existing treatments. Here, we present the development and evaluation of a novel super-multivalent sialyllactosylated filamentous phage, termed t-6SLPhage, as a potent entry blocker for influenza A viruses. Structural variations in sialyllactosyl ligands, including linkage type, valency, net charge, and spacer length, were systematically explored to identify optimal binding characteristics against target hemagglutinins and influenza viruses. The selected SLPhage equipped with optimal ligands, exhibited exceptional inhibitory potency in in vitro infection inhibition assays. Furthermore, in vivo studies demonstrated its efficacy as both a preventive and therapeutic intervention, even when administered post-exposure at 2 days post-infection, under 4 lethal dose 50% conditions. Remarkably, co-administration with oseltamivir revealed a synergistic effect, suggesting potential combination therapies to enhance efficacy and mitigate resistance. Our findings highlight the efficacy and safety of sialylated filamentous bacteriophages as promising influenza inhibitors. Moreover, the versatility of M13 phages for surface modifications offers avenues for further engineering to enhance therapeutic and preventive performance.

Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles.

Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections.

Applications and challenges of photodynamic therapy in the treatment of skin malignancies.

Photodynamic Therapy (PDT), as a minimally invasive treatment method, has demonstrated its distinct advantages in the management of skin malignant tumors. This article examines the current application status of PDT, assesses its successful cases and challenges in clinical treatment, and anticipates its future development trends. PDT utilizes photosensitizers to interact with light of specific wavelengths to generate reactive oxygen species that selectively eradicate cancer cells. Despite PDT's exceptional performance in enhancing patients' quality of life and prognosis, the limitation of treatment depth and the side effects of photosensitizers remain unresolved issues. With the advancement of novel photosensitizers and innovative treatment technology, the application prospects of PDT are increasingly expansive. This article delves into the mechanism of PDT, its application in various skin malignancies, its advantages and limitations, and envisions its future development. We believe that through continuous technological enhancements and integration with other treatment technologies, PDT has the potential to assume a more pivotal role in the treatment of skin malignancies.

Utilization of phase I studies for target validation of first-in-class drugs.

This review discusses the growing importance of target validation within phase I (P1) trials as a new trend in drug development, especially in establishing proof of concept (POC) for first-in-class drugs. The paper describes two approaches: the P1-PIV approach, which directly evaluates the primary end point for a pivotal clinical study to confirm therapeutic effects during P1, and the newly introduced P1-FCTE, which assesses functional changes necessary for therapeutic effect as a novel target validation milestone in P1. By providing practical examples of first-in-class drugs, we compare the benefits, costs, hurdles and applicable therapeutic areas of these approaches. Finally, we discuss the potential of these novel approaches to facilitate POC success, shorten development timelines and ultimately increase drug discovery success rates.

Fondaparinux sodium combined with conventional therapy improves subchorionic hematoma with protein S deficiency.

BACKGROUND: Fondaparinux sodium can prevent and treat acute illnesses and venous thromboembolism in patients undergoing surgery. At present, no studies have reported on treating subchorionic hematoma combined with protein S deficiency using fondaparinux sodium. OBJECTIVE: To investigate the clinical efficacy of fondaparinux sodium in the treatment of patients with subchorionic hematoma combined with protein S deficiency. METHODS: This single-center, open-ended, and prospective study enrolled 78 patients with subchorionic hematoma and protein S deficiency. They were randomly assigned to the treatment and control groups. The control group received conventional treatment, and the observation group received subepithelial injections of fondaparinux sodium (2.5 mg/day) based on conventional treatment. After 30 days of continuous treatment, the hematoma was evaluated by ultrasonography. RESULTS: After treatment with fondaparinux sodium, a significant improvement in subchorionic hematoma was observed in the observation group compared with that in the control group (p< 0.05). A substantial improvement in prothrombin time and activated partial thromboplastin time was observed in the observation group after fondaparinux sodium treatment (p< 0.05). Furthermore, after fondaparinux sodium treatment, the duration of hematoma maintenance and incidence of adverse pregnancy outcomes were significantly reduced in the observation group compared with that in the control group (p< 0.05). CONCLUSION: With a favorable safety profile, fondaparinux sodium is effective in treating subchorionic hematoma combined with protein S deficiency. The results provide new ideas and methods for treating this disease, which is worthy of further promotion and application in clinical practice.

Vibration-Induced Illusory Movement Task Can Induce Functional Recovery in Patients With Subacute Stroke.

In recent years, mental practice (MP), which involves repetitive motor imagery (MI), has been applied in rehabilitation to actively enhance exercise performance. MP is a method that involves repetitive MI, consciously evoking the intentions and content of the exercise without actual exercise. Combining actual exercise with MP promotes the development of exercise skills. However, it is possible that the MI recall ability differs greatly between individuals, affecting the therapeutic effect. In contrast, the vibration-induced illusory movement (VIM) task acts as a method to induce a motor illusion by somatosensory stimuli without actual motor. VIM, actual movement, and MI are thought to share a common neural basis in the brain. Therefore, it was hypothesized that the VIM task would complement the differences in MI recall in individual patients with hemiplegic stroke and may be a new treatment to enhance MI recall. Accordingly, in this study, we investigated the therapeutic effects of the VIM task in patients with hemiplegic stroke. In Study I, the therapeutic effect of the VIM task in 14 patients with post-stroke hemiplegia was evaluated by motor function assessment. In Study II, treatment effects were investigated by examining the ability of the same group of patients to recall MI and by neurophysiological examination of the electroencephalogram (EEG) during MI recall in four patients who consented to the study. Motor function and MI were assessed four times: before the intervention, after occupational therapy, after the VIM task (which used the motor illusion induced by tendon vibration), and one month after acceptance of therapy. Compared with occupational therapy, the VIM task showed a statistically significant improvement in upper limb function and MI ability. In addition, we found an increase in event-related desynchronization intensity during MI in the affected hemisphere only after the VIM task. It is possible that the VIM task facilitates motor function and MI. VIM task implementation of MI recall variability between individuals, which is a problem in mental practice, possible to increase the effectiveness of the brain-machine interface.

Insulin aspart plus high-dose vitamin D supplementation for gestational diabetes mellitus: analysis of efficacy and risk factors for maternal and infant outcomes.

BACKGROUND: Gestational diabetes mellitus (GDM) presents not only immediate challenges affecting maternal and infant health but also long-term consequences. Effective prevention and treatment of GDM are crucial for minimizing the short- and long-term health impacts. OBJECTIVES: This retrospective study evaluated the effects of insulin aspart injection plus high-dose vitamin D (HD-VD) supplementation on treatment outcomes and maternal - infant outcomes in patients with GDM. METHODS: A total of 129 GDM patients admitted to the Zhongshan Hospital Xiamen University from December 2021 to December 2023 were included in this study. According to the intervention regimen, the patients were divided into two groups: a control group of 59 patients receiving insulin aspart injection plus low-dose vitamin D (LD-VD) supplementation and a research group of 70 cases receiving insulin aspart injection plus HD-VD supplementation. The curative effect, blood glucose metabolism (fasting blood glucose [FPG], 2-hour postprandial blood glucose [2hPG], and glycosylated hemoglobin [HbA1c]), homocysteine (HCY), and cystatin C (Cys C), maternal and infant outcomes (maternal outcomes: hypoglycemia, cesarean section, polyhydramnios, and premature rupture of membranes; neonatal outcomes: stillbirth, macrosomia, neonatal respiratory distress syndrome, and Apgar score) were recorded and compared between the two groups. Risk factors affecting maternal and infant outcomes were analyzed. RESULTS: The research group demonstrated a higher overall effective rate in compared to the control group (P<0.05). Post-treatment measurements of FPG, 2hPG, HbA1c, HCY, and Cys C in the research group were statistically lower than the pre-treatment levels and those in the control group (all P<0.05). Additionally, the research group showed better maternal and neonatal outcomes, with fewer adverse pregnancy-related conditions and better neonatal health indicators, including higher Apgar scores (P<0.05). Besides, insulin aspart injection plus high-dose vitamin D was a protective factor for maternal and infant outcomes (P<0.05). CONCLUSIONS: Insulin aspart injection plus HD-VD supplementation markedly enhances treatment efficacy and improves maternal and infant outcomes in GDM.

Therapeutic effect of oxidized bletilla striata polysaccharide-natamycin eye drops on fungal keratitis.

OBJECTIVE: Fungal keratitis (FK) usually develops to a poor clinical prognosis due to the fungal invasion and excessive inflammatory reaction. In order to enhance the therapeutic effect of natamycin (NAT), we used the anti-inflammatory biological polysaccharide bletilla striata polysaccharide (BSP) combined with NAT to prepare a new eye drop -- oxidized bletilla striata polysaccharide-natamycin (OBN). METHODS: UV-vis, FT-IR, and fluorescence spectroscopy were used to identify the synthesis of OBN. Biocompatibility of OBN was determined by CCK-8, scratch assay, and corneal toxicity test. RAW264.7 cells and C57BL/6 mice were stimulated with A. fumigatus and treated with PBS, OBN, or NAT. The anti-inflammatory activity of OBN was detected by RT-PCR and ELISA. In mice with FK, the clinical scores were used to evaluate the effect of OBN; HE staining was performed to assess the corneal pathological changes; MPO assay and immunofluorescence staining were used to investigate neutrophil infiltration. RESULTS: OBN was synthesized by combining oxidized bletilla striata polysaccharide (OBSP) with NAT through Schiff base reaction. OBN did not affect cell viability at a concentration of 160 µg/mL in HCECs, RAW264.7 cells, and mouse corneas. OBN versus NAT significantly improved the prognosis of A. fumigatus keratitis by reducing disease severity, neutrophil infiltration, and expression of inflammatory factors in vivo. Additionally, OBN treatment down-regulated the mRNA and protein expression levels of inflammatory factors IL-1ß, TNF-α, and IL-6 in RAW264.7 and mouse models. CONCLUSION: OBN is a compound prepared by covalently linking OBSP to the imino group of NAT through Schiff base reaction. OBN treatment down-regulated inflammation and improved the prognosis of mice with A. fumigatus keratitis.

The efficacy of nebulized budesonide and ambroxol hydrochloride in treating pediatric community-acquired pneumonia and their impact on clinical characteristics and inflammatory markers.

PURPOSE: To evaluate the therapeutic efficacy of intravenous amoxicillin clavulanate potassium combined with nebulized budesonide and ambroxol hydrochloride in pediatric community-acquired pneumonia (CAP) and its impact across various microbial strains and clinical symptoms. The primary objective of this study is to evaluate the efficacy of intravenous amoxicillin-clavulanate combined with nebulized budesonide and ambroxol hydrochloride in the treatment of pediatric community-acquired pneumonia (CAP), and to analyze their impact on different microbial strains and clinical symptoms. Secondary objectives include assessing the treatment's effect on the improvement of clinical symptoms, hospital stay duration, and the levels of inflammatory markers. DESIGN: Prospective, single-center study. METHODS: Fifty-six children with CAP, aged under 6 years, from Affiliated Maternity and Child Health Care Hospital of Nantong University were included. Patients were treated with conventional therapy and the study medication. Clinical characteristics, microbiological data, symptom improvement, and hospitalization times were analyzed. FINDINGS: Young children, particularly under 1 year, exhibited a higher incidence of multiple microbial infections and severe clinical manifestations. Treatment with budesonide and ambroxol hydrochloride led to significant clinical improvement across all age groups, with notable efficacy against various pathogens. CONCLUSIONS: Nebulized budesonide and ambroxol hydrochloride are effective in treating pediatric CAP, offering a promising therapeutic option, particularly for young children with severe presentations.

Macromolecular Polymer Based Complexes: A Diverse Strategy for the Delivery of Nucleotides.

This review explores the burgeoning field of macromolecular polymer-based complexes, highlighting their revolutionary potential for the delivery of nucleotides for therapeutic applications. These complexes, ingeniously crafted from a variety of polymers, offer a unique solution to the challenges of nucleotide delivery, including protection from degradation, targeted delivery, and controlled release. The focus of this report is primarily on the design principles, encapsulation strategies, and biological interactions of these complexes, with an emphasis on their biocompatibility, biodegradability, and ability to form diverse structures, such as nanoparticles and micelles. Significant attention is paid to the latest advancements in polymer science that enable the precise tailoring of these complexes for specific nucleotides, such as DNA, RNA, and siRNA. The review discusses the critical role of surface modifications and the incorporation of targeting ligands in enhancing cellular uptake and ensuring delivery to specific tissues or cells, thereby reducing off-target effects and improving therapeutic efficacy. Clinical applications of these polymer-based delivery systems are thoroughly examined with a focus on their use in treating genetic disorders, cancer, and infectious diseases. The review also addresses the challenges and limitations currently faced in this field, such as scalability, manufacturing complexities, and regulatory hurdles. Overall, this review provides a comprehensive overview of the current state and future prospects of macromolecular polymer-based complexes in nucleotide delivery. It underscores the significance of these systems in advancing the field of targeted therapeutics and their potential to reshape the landscape of medical treatment for a wide range of diseases.

Retrospective Study on the Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation Combined with Tiapride Hydrochloride Tablets in Children with Attention Deficit Hyperactivity Disorder.

Objective: This study aimed to explore the application effect of repetitive transcranial magnetic stimulation (rTMS) combined with tiapride hydrochloride tablets in children with attention deficit hyperactivity disorder (ADHD). Methods: The medical records of 197 children with ADHD in our hospital from January 2022 to January 2023 were retrospectively analysed. Seven children who did not meet the inclusion criteria were excluded, and 190 children were finally included in this retrospective study. Based on the different clinical therapeutic methods, these children were divided into tiapride (n = 64), rTMS (n = 64), and combination (n = 62) groups. The clinical effects of different therapeutic schemes were compared. The clinical effectiveness and the scores of Swanson, Nolan, and Pelham Rating Scale Version IV (SNAP-IV), Conners Parent Symptom Questionnaire (PSQ), and Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) were compared among the 3 groups. Results: There was no significant difference in gender, age, course of disease, weight, and WISC-IV score among the combination, tiapride, and rTMS groups (all P > .05). The effective rate of treatment in the combination group (93.55%) was significantly higher than that in the tiapride group (78.13%) and the rTMS group (81.25%). There was a significant difference in the comparison of the combination group with the tiapride group (P = .013) and the rTMS group (P = .038). Before treatment, no significant difference existed in the scores of attention deficit symptoms and hyperactivity disorder symptoms among the 3 groups (all P > .05). After 3 months of treatment, the difference score of the combination group before and after treatment was significantly higher than that of other 2 groups (all P < .001). Before treatment, no significant difference was found in the scores of conduct problems, learning problems, psychosomatic disorders, impulsive hyperactivity, anxiety and hyperactivity index among the 3 groups (all P > .05). After treatment, the combination group had significantly higher difference score before and after treatment than other 2 groups (all P < .001). There was no significant difference in WFIRS-P scores among the 3 groups before treatment (all P > .05). After treatment, the difference score in the combination group before and after treatment was significantly higher compared with other 2 groups (all P < .001). Conclusion: Transcranial magnetic stimulation combined with tiapride hydrochloride tablets had a positive effect on improving the condition of children with ADHD, with certain clinical promotion value.

Florfenicol core-shell composite nanogels as oral administration for efficient treatment of bacterial enteritis.

To reduce the bitterness of florfenicol, avoid its degradation by gastric acid, and enhance its antibacterial activity against Escherichia coli by targeting and slowly releasing drugs at the site of intestinal infection, with pectin as an anion carrier and chitosan oligosaccharides (COS) as a cationic carrier, florfenicol-loaded COS@pectin core nanogels were self-assembled by electrostatic interaction and then encapsulated in sodium carboxymethylcellulose (CMCNa) shell nanogels through the complexation of CMCNa and Ca2+ to prepare florfenicol core-shell composite nanogels in this study. The florfenicol core-shell composite nanogels were investigated for their formula choice, physicochemical characterization, pH-responsive performances, antibacterial activity, therapeutic efficacy, and in vitro and in vivo biosafety studies. The results indicated that the optimized formula was 0.6 g florfenicol, 0.79 g CMCNa, 0.30 g CaCl2, 0.05 g COS, and 0.10 g pectin, respectively. In addition, the mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 124.0 ± 7.2 nm, -22.9 ± 2.5 mV, 0.42 ± 0.03, 43.4 % ± 3.1 %, and 80.5 % ± 3.4 %, respectively. The appearance, lyophilized mass, resolvability, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and fourier transform infrared (FTIR) showed that the florfenicol core-shell composite nanogels were successfully prepared. Florfenicol core-shell composite nanogels had satisfactory stability, rheology, and pH-responsiveness, which were conducive to avoid degradation by gastric acid and achieve targeted and slow release at intestinal infection sites. More importantly, florfenicol core-shell composite nanogels had excellent antibacterial activity against Escherichia coli, a satisfactory therapeutic effect, and good palatability. In vitro and in vivo biosafety studies suggested the great promise of florfenicol core-shell composite nanogels. Therefore, the prepared florfenicol core-shell composite nanogels may be helpful for the treatment of bacterial enteritis as a biocompatible oral administration.

Accumulation of CD56+ CD16- Natural Killer Cells in Response to Preoperative Chemotherapy for Breast Cancer.

Background: The activation of the antitumor immune responses of T cells and natural killer (NK) cells is important to induce breast tumor shrinkage via preoperative chemotherapy. We evaluated how antitumor immune responses contribute to the effects of such therapy. Methods: Forty-three patients with stages I - IV breast cancer who underwent surgery between August 2018 and Jun 2023 after preoperative chemotherapy were enrolled. Peripheral natural killer (pNK) cell activity was assessed by 51Cr-release assay, and the counts and percentages of CD4+, CD8+, and NK cells and their subsets in peripheral blood were measured before and after chemotherapy by two-color flow cytometry. Associations of cell population changes with chemotherapy responses were analyzed. Results: On univariate analysis, relative to grade (G) ≤ 1 effects, G ≥ 2 therapeutic effects were associated significantly with human epidermal growth factor receptor 2 (HER-2)+ breast cancer (P = 0.024) and post-chemotherapy CD56+ CD16- NK cell accumulation (8.4% vs. 5.5%, P = 0.042), and tended to be associated with increased pre-chemotherapy CD56+ CD16- NK cell percentages (5.4% vs. 3.3%, P = 0.054) and pNK cell activity (42.0% vs. 34.5%, P = 0.057). The accumulation and increased percentage of CD56+ CD16- NK cells in patients with G ≥ 2 effects were not associated with changes in pNK cell activity or the disappearance of axillary lymph-node metastases. On multivariate analysis, G ≥ 2 therapeutic effects tended to be associated with higher pre-chemotherapy pNK levels (odds ratio = 0.96; 95% confidence interval: 0.921 - 1.002; P = 0.067). Conclusions: The accumulation of the immunoregulatory CD56+ CD16- NK cell subset in the peripheral blood before and after chemotherapy may lead to the production of cytokines that induce an antitumor immune response. Activation of the immune response mediated by CD56+ CD16- pNK cells after chemotherapy and their high counts before chemotherapy may contribute to the improvement of therapeutic effects against breast cancer.

Analysis of effect of colonoscopy combined with laparoscopy in the treatment of colorectal tumors.

BACKGROUND: Colorectal cancer is one of the most common digestive tract tumors. OBJECTIVE: To evaluate the feasibility and safety of laparoscopic colorectal cancer surgery. METHODS: This study retrospectively analyzed early postoperative clinical data of 48 patients with colorectal cancer treated in our hospital between 2015 and 2021, of which 21 underwent laparoscopic colorectal surgery, and 27 underwent laparotomy. There was no significant difference in clinical data. Patients were included if they had colorectal cancer (confirmed by colonoscopy and biopsy pathological examination before surgery), were evaluated for possible radical surgery before surgery, and had no intestinal obstruction, tumor invasion of adjacent organs (by digital rectal examination and preoperative abdominal color Doppler ultrasound, CT confirmed) and no other history of abdominal surgery. Using the method of clinical control study, operation time, intraoperative blood loss, postoperative general condition, surgical lymph node removal (postoperative pathology), surgical complications, gastrointestinal function recovery, surgical before and after blood glucose, body temperature, white blood cells, pain visual analog scale (VAS) and other conditions were compared and analyzed to determine feasibility and safety of laparoscopic surgery for colorectal cancer. RESULTS: Colorectal cancer was successfully removed by laparoscopic radical resection without any significant problems or surgical fatalities. Age, gender, tumor location, stage, and duration of surgery did not differ between laparoscopic and laparotomy operations. Compared to laparotomy, postoperative eating, bowel movements, and blood sugar levels improved. Variations in the length of surgically removed specimens after VAS measurements revealed open and laparoscopic operations. The overall lymph node count was 10.8 ± 1.6, with no variation between the two techniques. CONCLUSION: Laparoscopic colorectal cancer radical surgery is safe and feasible. Also, it has the advantages of minimally invasive surgery. Laparoscopic colorectal cancer radical surgery can comply with the principles of oncology revolutionary.

Therapeutic effect of induction therapy including nab-paclitaxel followed by surgical resection for the patients with locally advanced non-small-cell lung cancer.

BACKGROUND: Lung cancer is associated with a high mortality rate worldwide. Non-small-cell lung cancer (NSCLC) is a major subtype of lung cancer. Carboplatin (CBDCA) plus nab-paclitaxel (PTX) has become a standard treatment for advanced unresectable NSCLC. However, treatment with nab-PTX has not been established as a standard therapy for resectable locally advanced (LA)-NSCLC. METHODS: We conducted a comprehensive study involving consecutive patients with locally advanced NSCLC who underwent induction therapy including nab-PTX followed by surgical resection. Fifteen patients with locally advanced NSCLC underwent induction therapy including nab-PTX followed by surgical resection. Concurrent chemoradiotherapy (CRT) consisted of weekly administration of nab-PTX (50 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (50 Gy/25 fractions). RESULTS: The clinical stages were as follows: IIB (n =1), IIIA (n =12), and IIIC (n =2). Downstaging was observed in 73% (11/15) of patients on comparison with the clinical stage before concurrent CRT. Adverse drug reactions were observed in seven patients. Complete resection was performed in all patients. The re-evaluated pathological stage after pretreatment was diagnosed as stage 0 in three patients, stage IA1 in six, stage IA2 in one, and stage IIIA in five. The pathological effects of previous therapy were as follows: Ef3 (n =3), Ef2 (n =9), and Ef1a (n =3). CONCLUSION: The therapeutic effect of induction therapy including nab-PTX was promising. Induction CRT, including nab-PTX, followed by resection, may be a viable alternative treatment option for locally advanced NSCLC.

Observation of therapeutic effect of lamp irradiation combined with purple gromwell oil gauze on alleviating intestinal colic in patients.

BACKGROUND: Intestinal colic is a common complication in patients who have undergone radical surgery for colorectal cancer. Traditional Chinese medicine has advantages, including safety and stability, for the treatment of intestinal colic. Lamp irradiation for abdominal ironing has been applied in the treatment of many gastrointestinal diseases. Purple gromwell oil has the effects of clearing heat, cooling blood, reducing swelling, and relieving pain. AIM: To investigate the impact of lamp irradiation combined with purple gromwell oil gauze on ameliorating intestinal colic in patients after radical surgery for colorectal cancer. METHODS: A total of 120 patients who experienced postoperative intestinal colic complications after radical surgery for colorectal cancer and who were admitted to Foshan Traditional Chinese Medicine Hospital between June 2019 and March 2023 were enrolled as study subjects. The patients were divided into a control group (60 patients) and an observation group (60 patients) based on treatment method. The control group was treated with lamp irradiation, while the observation group was treated with lamp irradiation and external application of purple gromwell oil gauze. The clinical efficacy, Numeric Rating Scale (NRS) score, duration of symptoms, and rate of adverse reaction occurrence were further compared between the two groups. RESULTS: The general effective rate in the observation group was 95.00%, which was significantly higher than that in the control group (86.67%, P < 0.05). Before treatment, there was no significant difference in the duration of symptoms between the groups (P > 0.05). After 1, 2, 3, and 4 d of treatment, the duration of symptoms in both groups were decreased, and the duration in the observation group was significantly lower than that in the control group (96.54 ± 9.57 vs 110.45 ± 11.23, 87.26 ± 12.07 vs 104.44 ± 11.68, 80.45 ± 16.21 vs 99.44 ± 14.95, 73.18 ± 15.58 vs 92.17 ± 14.20; P < 0.05). After 1, 3, 5, and 7 d of treatment, the NRS scores in both groups were decreased, and the NRS scores in the observation group were significantly lower than those in the control group (3.56 ± 0.41 vs 4.04 ± 0.58, 3.07 ± 0.67 vs 3.74 ± 1.02, 2.52 ± 0.76 vs 3.43 ± 0.85, 2.03 ± 0.58 vs 3.03 ± 0.82; P < 0.05). There was no significant difference in the rate of adverse reaction occurrence between the groups (P > 0.05). CONCLUSION: The use of lamp irradiation combined with purple gromwell oil gauze in patients with intestinal colic after radical surgery for colorectal cancer can reduce symptom duration, alleviate intestinal colic, and improve treatment efficacy, and this approach is safe. It is worth promoting the use of this treatment in clinical practice.

Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306.

BACKGROUND: In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis. METHODS: We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined. RESULTS: ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175-0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073-0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is. CONCLUSIONS: RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.

Advances in research on factors affecting chimeric antigen receptor T-cell efficacy.

Chimeric antigen receptor T-cell (CAR-T) therapy is becoming an effective technique for the treatment of patients with relapsed/refractory hematologic malignancies. After analyzing patients with tumor progression and sustained remission after CAR-T cell therapy, many factors were found to be associated with the efficacy of CAR-T therapy. This paper reviews the factors affecting the effect of CAR-T such as tumor characteristics, tumor microenvironment and immune function of patients, CAR-T cell structure, construction method and in vivo expansion values, lymphodepletion chemotherapy, and previous treatment, and provides a preliminary outlook on the corresponding therapeutic strategies.

Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway.

The spreading of cancer cells from the primary tumor site to other parts of the body, known as metastasis, is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer (TNBC). Overexpression of epidermal growth factor receptor (EGFR) is observed in approximately 70% of TNBC patients. EGFR is crucial for promoting tumor metastasis and associated with poor prognosis. Therefore, it is vital to identify effective therapeutic strategies targeting EGFR inhibition. Ononin, an isoflavonoid found in various plants, such as clover and soybeans, has been shown to have anticancer properties in several cancers. In the present study, we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular pathways. We used various assays, including cell viability, colony formation, Transwell, wound healing, ELISA, Western blotting, and staining techniques, to achieve this objective. The results demonstrated that ononin effectively suppressed cellular proliferation and induced apoptosis, as evidenced by the cell viability assay, colony formation assay, and expression of apoptosis markers, and reduced the metastatic capabilities of TNBC cells. These effects were achieved through the direct suppression of cell adhesion, invasiveness and motility. Furthermore, in TNBC xenograft lung metastatic models, ononin treatment significantly reduced tumor growth and lung metastasis. Additionally, ononin reversed the epithelial-mesenchymal transition (EMT) by downregulating the expression of EMT markers and matrix metalloproteinases, as confirmed by Western blot analysis. Furthermore, ononin treatment reduced EGFR phosphorylation and suppressed the PI3K, Akt, and mTOR signaling pathways, which was further confirmed using EGFR agonists or inhibitors. Importantly, ononin treatment did not exert any toxic effects on liver or kidney function. In conclusion, our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFR-mediated PI3K/Akt/mTOR pathway. Further studies are warranted to validate its efficacy and explore its potential clinical applications.

Therapeutic effect and mechanisms of traditional Chinese medicine compound (Qilong capsule) in the treatment of ischemic stroke.

Background Qilong capsule (QLC) is a well-known traditional Chinese medicine compound extensively used in clinical practice. It has been approved by the China's FDA for the treatment of ischemic stroke (IS). In our clinical trial involving QLC (ClinicalTrials.gov identifier: NCT03174535), we observed the potential of QLC to improve neurological function in IS patients at the 24th week, while ensuring their safety. However, the effectiveness of QLC beyond the initial 12-week period remains uncertain, and the precise mechanisms underlying its action in IS have not been fully elucidated. Purpose In order to further explore the clinical efficacy of QLC in treating IS beyond the initial 12-week period and systematically elucidate its underlying mechanisms. Study Design This study employed an interdisciplinary integration strategy that combines post hoc analysis of clinical trials, transcriptome sequencing, integrated bioinformatics analysis, and animal experiments. Methods In this study, we conducted a post-hoc analysis with 2302 participants to evaluate the effectiveness of QLC at the 12th week. The primary outcome was the proportion of patients achieving functional independence at the 12th week, defined as a score of 0-2 on the modified Rankin Scale (mRS), which ranges from 0 (no symptoms) to 6 (death). Subsequently, we employed RNA sequencing (RNA-Seq) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) techniques in the QLC trial to investigate the potential molecular mechanisms underlying the therapeutic effect of QLC in IS. Simultaneously, we utilized integrated bioinformatics analyses driven by external multi-source data and algorithms to further supplement the exploration and validation of QLC's therapeutic mechanism in treating IS. This encompassed network pharmacology analysis and analyses at the mRNA, cellular, and pathway levels focusing on core targets. Additionally, we developed a disease risk prediction model using machine learning. By identifying differentially expressed core genes (DECGs) between the normal and IS groups, we quantitatively predicted IS occurrence. Furthermore, to assess its protective effects and determine the key regulated pathway, we conducted experiments using a middle cerebral artery occlusion and reperfusion (MACO/R) rat model. Results Our findings demonstrated that the combination of QLC and conventional treatment (CT) significantly improved the proportion of patients achieving functional independence (mRS score 0-2) at the 12th week compared to CT alone (n = 2,302, 88.65 % vs 87.33 %, p = 0.3337; n = 600, 91.33 % vs 84.67 %, p = 0.0165). Transcriptome data revealed that the potential underlying mechanism of QLC for IS is related to the regulation of the NF-κB inflammatory pathway. The RT-qPCR results demonstrated that the regulatory trends of key genes, such as MD-2, were consistent with those observed in the RNA-Seq analysis. Integrated bioinformatics analysis elucidated that QLC regulates the NF-κB signaling pathway by identifying core targets, and machine learning was utilized to forecast the risk of IS onset. The MACO/R rat model experiment confirmed that QLC exerts its anti-CIRI effects by inhibiting the MD-2/TLR-4/NF-κB signaling axis. Conclusion: Our interdisciplinary integration study has demonstrated that the combination of QLC with CT exhibits significant superiority over CT alone in improving functional independence in patients at the 12th week. The potential mechanism underlying QLC's therapeutic effect in IS involves the inhibition of the MD-2/TLR4/NF-κB inflammatory signaling pathway, thereby attenuating cerebral ischemia/reperfusion inflammatory injury and facilitating neurofunctional recovery. The novelty and innovative potential of this study primarily lie in the novel finding that QLC significantly enhances the proportion of patients achieving functional independence (mRS score 0-2) at the 12th week. Furthermore, employing a "multilevel-multimethod" integrated research approach, we elucidated the potential mechanism underlying QLC's therapeutic effect in IS.