Small cell lung cancer (SCLC) constitutes approximately 10% to 15% of all lung cancer diagnoses and represents a pressing global public health challenge due to its high mortality rates. The efficacy of conventional treatments for SCLC is suboptimal, characterized by limited anti-tumoral effects and frequent relapses. In this context, emerging research has pivoted towards immunotherapy combined with chemotherapy, a rapidly advancing field that has shown promise in ameliorating the clinical outcomes of SCLC patients. Through originally developed for non-small cell lung cancer (NSCLC), these therapies have extended new treatment avenues for SCLC. Currently, a nexus of emerging hot-spot treatments has demonstrated significant therapeutic efficacy. Based on the amalgamation of chemotherapy and immunotherapy, and the development of new immunotherapy agents, the treatment of SCLC has seen the hoping future. Progress has been achieved in enhancing the tumor immune microenvironment through the concomitant use of chemotherapy, immunotherapy, and tyrosine kinase inhibitors (TKI), as evinced by emerging clinical trial data. Moreover, a tripartite approach involving immunotherapy, targeted therapy, and chemotherapy appears auspicious for future clinical applications. Overcoming resistance to post-immunotherapy regimens remains an urgent area of exploration. Finally, bispecific antibodies, adoptive cell transfer (ACT), oncolytic virus, monotherapy, including Delta-like ligand 3 (DLL3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), as well as precision medicine, may present a prospective route towards achieving curative outcomes in SCLC. This review aims to synthesize extant literature and highlight future directions in SCLC treatment, acknowledging the persistent challenges in the field. Furthermore, the continual development of novel therapeutic agents and technologies renders the future of SCLC treatment increasingly optimistic.

OBJECTIVE: We hypothesized that combination therapy would provide a synergistic effect to improve treatment outcomes for overactive bladder (OAB), thus enhancing the motivation for continuous exercise, and that it would be associated with fewer adverse events than monotherapy. Therefore, we investigated whether biofeedback-assisted pelvic floor muscle training (PFMT), drug therapy, or a combination of both would be more effective in improving the symptoms of OAB.
METHODS: This randomized controlled trial included women diagnosed with OAB. Group 1 received biofeedback-assisted pelvic muscle floor training (PFMT) for 12 weeks; group 2 took 5 mg of solifenacin/day for 12 weeks; and group 3 received 5 mg of solifenacin/day in combination with biofeedback-assisted PFMT during the first 4 weeks and biofeedback-assisted PFMT for another 8 weeks. All participants had 5 follow-up visits. The primary outcomes were objective improvement of OAB symptoms and quality of life. The secondary outcomes were treatment-related adverse events, subjective improvement of OAB symptoms, and electromyographic activity of pelvic floor muscle (PFM) contraction.
RESULTS: All participants reported significant improvement of OAB symptoms and quality of life. Participants in group 2 experienced more pronounced adverse events than those in group 3. Intervention duration was positively associated with subjective improvement in OAB symptoms in groups 2 and 3. Drug-related adverse events, including dry mouth, myalgia, and restlessness, had a negative impact on the subjective improvement of OAB symptoms in group 2. In group 1, exercise adherence was positively correlated with subjective improvement of OAB symptoms, whereas in group 3, PFM contraction and biofeedback effect were positively correlated with symptom improvement.
CONCLUSIONS: Combination therapy is efficacious in treating women with OAB.

More than half of stroke survivors suffer from upper-limb dysfunction that persists years after stroke, negatively impacting patients\' independence and, therefore, affecting their quality of life. Intense motor rehabilitation is required after a stroke to facilitate motor recovery. More importantly, finding new ways to maximize patients\' motor recovery is a core goal of stroke rehabilitation. Thus, researchers have explored the potential benefits of combining the effects of non-invasive brain stimulation with physical therapy rehabilitation. Specifically, combining transcranial direct stimulation (tDCS) with neurorehabilitation interventions can boost the brain\'s responses to interventions and maximize the effects of rehabilitation to improve upper-limb recovery post-stroke. However, it is still unclear which modes of tDCS are optimal for upper-limb motor recovery in patients with stroke when combined with physical therapy interventions. Here, the authors review the existing literature suggesting combining physical therapy rehabilitation with tDCS can maximize patients\' motor recovery using the Interhemispheric Competition Model in Stroke. The authors focus on two main rehabilitation paradigms, which are constraint-induced movement therapy (CIMT) and Mirror therapy with and without tDCS. The authors also discuss potential studies to elucidate further the benefit of using tDCS adjunct with these upper-limb rehabilitation paradigms and its effectiveness in patients with stroke, with the ultimate goal of maximizing patients\' motor recovery.

Radioimmunotherapy (RIT) is a novel and promising cancer treatment method, with ongoing research focusing on RIT antibody selection, radionuclides, treatment options, and benefited patient groups. As we dive into the mechanisms of tumor biology, a deeper exploration of how RIT affects tumor tissue is needed to provide new ways to improve clinical treatment outcome and patient prognosis. We labeled the anti-PD-L1 monoclonal antibody atezolizumab with iodine-131 (131I), separated and purified the labeled mAb with Sephadex G-25 medium gel filtration resin, and tested product stability. We detected the in vivo activity of 131I-PD-L1 mAb by analyzing its in vivo biodistribution and performing SPECT imaging and then set different treatment groups to study the effect of 131I-atezolizumab on the survival of tumor-bearing mice. Western blot, real-time quantitative PCR, and immunohistochemistry were used to detect the expression level of Caspase8 and Nlrp3 in tumor. TUNEL fluorescence staining was used to detect the apoptosis in the tumor. The radiopharmaceutical molecular probe 131I-atezolizumab showed high stability and in vivo biological activity. The treatment regimen adopted had a positive effect on the survival of tumor-bearing mice. 131I internal irradiation upregulated Caspase8 in tumor and ultimately inhibited solid tumor growth by activating apoptosis pathways. We also found a significant increase in the expression of NLRP3, which plays an important role in the pyroptosis pathway, in tumor. In summary, our data demonstrated that radiopharmaceuticals combined with immunotherapy affected tumor tissue by modulating relevant biological pathways, thereby achieving better antitumor effects compared with single therapy and providing new insights for promoting better patient prognosis and combination treatment strategies.

UNASSIGNED: The incidence of hypertension and clinical complications (e.g., heart, cerebrovascular and kidney injury) is increasing worldwide. It is widely known that a relatively large dose of valsartan (320 mg) could alleviate clinical complications. The current network meta-analysis assessed which drug could be combined with a relatively large dose of valsartan to control blood pressure (BP) more effectively. And which combination therapy with different dosages of valsartan did not induce excessive BP reduction with increasing dosages of valsartan.
UNASSIGNED: The PubMed, Embase, Medline, Cochrane Library, CNKI, Wanfang, and CSTJ databases were searched from inception to October 2022 for relevant randomized controlled trials (RCTs). The search strategies included concepts related to hypertension and two-drug combination therapy of different doses of valsartan, and there were no language or data restrictions. The outcomes included adverse effects and changes in systolic BP and diastolic BP. Permanent discontinuations related to treatment were the most accurate and objective measure of adverse effects. The common adverse effects of most studies (i.e., dizziness, headache, nasopharyngitis, asthenia and urticaria) were also included. A Bayesian network meta-analysis was performed, and mean differences with 95% confidence intervals were calculated. ADDIS and STATA were used for Bayesian model network meta-calculation.
UNASSIGNED: Thirty-four RCTs were included involving 26,752 patients, and the interventions included different doses of valsartan combined with various types and doses of drugs. Among many combination therapies, the combination of valsartan 320 mg with amlodipine 10 mg (p < 0.01) had the best antihypertensive effect without significant adverse effects. Compared with valsartan 80 mg and 160 mg, valsartan 320 mg combined with hydrochlorothiazide 25 mg (p > 0.05) did not further reduce BP and was not shown to increase the incidence of adverse effects.
UNASSIGNED: Combination therapy with a relatively large dose of valsartan could control BP and improve clinical complications effectively. However, for hypertensive patients with different treatment requirements, specific choices should be made regarding whether to control BP, treat clinical complications, or both.

Fonsecaea pedrosoi is a melanized fungus that causes chromoblastomycosis (CBM), a tropical neglected disease responsible for chronic and disability-related subcutaneous mycosis. Given the challenging nature of CBM treatment, the study of new targets and novel bioactive drugs capable of improving patient life quality is urgent. In the present work, we detected a calcineurin activity in F. pedrosoi conidial form, employing primarily colorimetric, immunoblotting and flow cytometry assays. Our findings reveal that the calcineurin activity of F. pedrosoi was stimulated by Ca2+/calmodulin, inhibited by EGTA and specific inhibitors, such as tacrolimus (FK506) and cyclosporine A (CsA), and proved to be insensitive to okadaic acid. In addition, FK506 and CsA were able to affect the cellular viability and the fungal proliferation. This effect was corroborated by transmission electron microscopy that showed both calcineurin inhibitors promoted profound changes in the ultrastructure of conidia, causing mainly cytoplasm condensation and intense vacuolization that are clear indication of cell death. Our data indicated that FK506 exhibited the highest effectiveness, with a minimum inhibitory concentration (MIC) of 3.12 mg/L, whereas CsA required 15.6 mg/L to inhibit 100% of conidial growth. Interestingly, when both were combined with itraconazole, they demonstrated anti-F. pedrosoi activity, exhibiting a synergistic effect. Moreover, the fungal filamentation was affected after treatment with both calcineurin inhibitors. These data corroborate with other calcineurin studies in fungal cells and open up further discussions aiming to establish the role of this enzyme as a potential target for antifungal therapy against CBM infections.

In the study, we aimed to investigate the activity of nanoformulations containing 5-fluorouracil and polymer-magnetic hybrids bearing membrane-penetrating and ligand-receptor-recognizing agents against colorectal cancer cells. The formation and characterization of iron oxide particles covered with polymeric shells comprising lithocholic acid and folic acid moieties are presented. The efficiency of nanoformulations combined by the simple mixing of low doses of 5-fluorouracil with the obtained hybrids was demonstrated against DLD-1 and HT-29 colon cancer cells. The most pronounced cytotoxic potential against HT-29 cells was observed in the cases of particles based on block and randomly arranged copolymers functionalized by FA motifs with depletion of viable cells by approximately 50 % compared to control cells and cells treated by 5-FU applied in free form. In the case of the DLD-1 cell line, the percentage of viable DLD-1 cells decreased by about 30 to 40% after treatment with the block and randomly arranged copolymer decorated by FA-moiety, when compared to 5-FU at the free form and the untreated control. The induction of apoptosis associated with PS-translocation was determined to be the main mechanism of their cytotoxic effects. Moreover, the safety profiles of the nanoformulations were established through hemolysis assay and the analysis of the viability of human colorectal fibroblasts. It was indicated that all tested nanoparticles met the compatibility requirements at the in vitro level. It should be emphasized that in many cases, there was a significant improvement in the compatibility of hybrids with the FA motif compared to non-functionalized hybrids with the addition of 5-FU. These findings suggest that the presence of FA might modulate the toxicity of chemotherapeutic agents.

Nowadays, oral medications are the primary method of treating disease due to their convenience, low cost, and safety, without the need for complex medical procedures. To maximize treatment effectiveness, almost all oral medications utilize drug carriers, such as capsules, liposomes, and sugar coatings. However, these carriers rely on dissolution or fragmentation to achieve drug release, which leads to drugs and carriers coabsorption in the body, causing unnecessary adverse drug reactions, such as nausea, vomiting, abdominal pain, and even death caused by allergy. Therefore, the ideal oral drug carrier should avoid degradation and absorption and be totally excreted after drug release at the desired location. Herein, a gastrointestinally stable oral drug carrier based on porous aromatic framework-1 (PAF-1) is constructed, and it is modified with famotidine (a well-known gastric drug) and mesalazine (a well-known ulcerative colitis drug) to verify the excellent potential of PAF-1. The results demonstrate that PAF-1 can accurately release famotidine in stomach, mesalazine in the intestine, and finally be completely excreted from the body without any residue after 12 h. The use of PAF materials for the construction of oral drug carriers with no residue in the gastrointestinal tract provides a new approach for efficient disease treatment.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have shown the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. Although additional in vivo studies are necessary, this study suggests that the combination therapy of abemaciclib and desipramine may represent a novel therapeutic approach for treating solid tumors.

OBJECTIVE: To observe the clinical efficacy of acupoint massage, acupoint sticking combined with moxibustion at Shuidao (ST 28) for postpartum urinary retention.
METHODS: A total of 120 patients with postpartum urinary retention were randomly divided a triple-combination group, a double-combination group, and a massage group, with 40 patients in each group. All groups received standard postpartum care to stimulate urination. The patients in the massage group received rapid acupoint massage at the bilateral Shuidao (ST 28); the patients in the double-combination group additionally received acupoint sticking of self-made Tongquan powder at bilateral Shuidao (ST 28); the patients in the triple-combination group further received moxibustion at bilateral Shuidao (ST 28). The treatment was given once in all three groups. After 5 hours of treatment completion, bladder residual volume was measured; the time and volume of first urination as well as total urination volume after 5 hours of treatment completion were recorded; the patients\' sensation of urination smoothness, satisfaction rate, length of hospital stay, and hospital costs were evaluated.
RESULTS: The triple-combination group showed significantly lower residual urine volumes (P<0.05), earlier first urination time (P<0.05, P<0.001), and higher first urination volumes and total urination volumes after 5 hours of treatment completion compared to the other two groups (P<0.05, P<0.001). The sensation of urination smoothness and patient satisfaction were also significantly better in the triple-combination group (P<0.001, P<0.05). The double-combination group had higher volume of first urination and total urination volume after 5 hours of treatment completion than the massage group (P<0.05), and better sensation of urination smoothness and patient satisfaction (P<0.05). There was no significant difference in the length of hospital stay and costs among the three groups (P>0.05). The total effective rates were 100.0% (40/40) for the triple-combination group, 90.0% (36/40) for the double-combination group, and 70.0% (28/40) for the massage group, with the triple-combination group significantly outperforming the other two groups (P<0.05, P<0.001), and double-combination group outperforming the massage group (P<0.05).
CONCLUSIONS: Acupoint massage, acupoint sticking combined with moxibustion at Shuidao (ST 28) could effectively improve urination in patients with postpartum urinary retention, and enhance patient satisfaction.
目的：观察于水道穴行穴位按摩、穴位贴敷联合艾灸治疗产后尿潴留的临床疗效。方法：将120例产后尿潴留患者随机分为三联组、两联组和按摩组，每组40例。3组均予产后常规护理刺激排尿。按摩组于双侧水道穴行快速按摩；两联组于按摩组基础上于双侧水道穴行自拟通泉散穴位贴敷；三联组于两联组基础上于双侧水道穴行艾灸干预。3组均治疗1次。治疗后5 h检测患者膀胱残余尿量，记录患者首次排尿时间、首次排尿量及治疗后5 h排尿总量，评价首次排尿通畅感和患者满意度，记录住院天数和住院费用，并评定3组临床疗效。结果：三联组患者膀胱残余尿量少于两联组及按摩组（P<0.05），首次排尿时间早于两联组及按摩组（P<0.05，P<0.001），首次排尿量、治疗后5 h排尿总量多于两联组及按摩组（P<0.05，P<0.001），首次排尿通畅感和患者满意度优于两联组及按摩组（P<0.001，P<0.05）；两联组患者首次排尿量、治疗后5 h排尿总量多于按摩组（P<0.05），首次排尿通畅感和患者满意度优于按摩组（P<0.05）。3组患者住院天数及住院费用比较差异无统计学意义（P>0.05）。三联组、两联组和按摩组总有效率分别为100.0％（40/40）、90.0％（36/40）和70.0％（28/40），三联组总有效率高于两联组及按摩组（P<0.05，P<0.001），两联组总有效率高于按摩组（P<0.05）。结论：于水道穴行穴位按摩、穴位贴敷联合艾灸治疗可有效改善产后尿潴留患者排尿情况，提高患者满意度。.