Clinical evidence for the prognostic impact of metformin in cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Preclinical studies suggest that metformin might enhance the efficacy of immune checkpoint inhibitors (ICIs) and potentially influence the prognoses of cancer patients undergoing ICIs treatment. This study endeavors to assess the prognostic significance of metformin in cancer patients undergoing ICIs therapy, aiming to furnish evidence-based insights for clinical practice. METHODS: A thorough literature search was conducted across electronic databases to encompass all potential records published before November 20th, 2023. A meta-analysis was executed utilizing Stata 17.0 to derive pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for both overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 22 studies encompassing 9,011 patients met the inclusion criteria. Meta-analyses revealed a significant correlation between metformin use and poorer OS (HR, 1.13; 95 %CI, 1.04-1.23; P = 0.004) rather than PFS (HR, 1.04; 95 %CI, 0.96-1.14; P = 0.345) among cancer patients undergoing ICIs treatment. Subgroup analysis delineated that the concurrent administration of metformin and ICIs significantly associated with adverse prognoses in the European population (OS: HR, 1.23; 95 %CI, 1.10-1.39; P = 0.001; PFS: HR, 1.14; 95 %CI, 1.02-1.28; P = 0.024). CONCLUSION: Based on current clinical evidence, concomitant metformin use does not appear to improve the prognostic outcomes for cancer patients undergoing ICIs therapy and may potentially correlate with inferior prognoses. Further studies are imperative to comprehensively elucidate the impact of metformin within the realm of ICIs therapy.

Young Sca-1+ bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization.

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.

Influence of optical zone on myopic correction in small incision lenticule extraction: a short-term study.

BACKGROUND: To evaluate the influence of preoperative optical zone on myopic correction in small incision lenticule extraction. METHODS: In this retrospective clinical study, 581 eyes from 316 patients underwent SMILE were selected, including 117 eyes in the small optical zone group (range from 6.0 to 6.4 mm) and 464 eyes in the large optical zone group (range from 6.5 to 6.8 mm). The measurements included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical, and cylinder were measured preoperatively and 3 months postoperatively. Propensity score match (PSM) analysis was performed with age, gender, eye (right/left), keratometry and preoperative spherical equivalent between two different groups. The influence of optical zones on postoperative refractive outcomes were evaluated using univariate regression analysis. RESULTS: In total, 78 pairs of eyes were selected by PSM (match ratio 1:1). There were no differences in the age, gender, eye (right/left), keratometry or preoperative spherical equivalent between the small and large optical zone groups. However, the difference of postoperative spherical equivalent was significantly between groups. Patients with larger optical zones had a trend towards less undercorrection (P = 0.018). Univariate linear regression model analysis found that each millimeter larger optical zone resulted in 8.13% or 0.39D less undercorrection (P < 0.001). The dependency between the optical zones and postoperative spherical equivalent was significant in the higher preoperative myopia group (r = 0.281, P < 0.001), but not significant in the lower myopia group (r = 0.028, P = 0.702). CONCLUSION: The diameter of optical zones would affect postoperative refractive outcomes in small incision lenticule extraction. This study indicated that larger optical zones induced less undercorrection, especially in patients with high myopia.

Nanocomplexes derived from chitosan and whey protein isolate enhance the thermal stability and slow the release of anthocyanins in simulated digestion and prepared instant coffee.

Anthocyanins (ACNs) are naturally derived colorants and antioxidants added to manufactured foods. ACNs were encapsulated in nanocomplexes with chitosan hydrochloride (CHC), carboxymethyl chitosan (CMC) and whey protein isolate (WPI). The ACN-loaded CHC/CMC-WPI nanocomplexes (ACN-CHC/CMC-WPI) showed a preferred particle size (332.20 nm) and zeta potential (+23.65 mV) and a high encapsulation efficiency (60.70%). ACN-CHC/CMC-WPI nanocomplexes exhibited a smooth spherical shape by transmission electron microscopy. Fourier transform infrared (FT-IR) and Raman spectroscopy confirmed interactions between the ACNs and the encapsulation materials (CHC/CMC-WPI). The nanocomplexes or the nanocomplexes incorporated into coffee beverage better protected ACNs at high temperature compared to the unencapsulated ACNs. In simulated gastrointestinal fluids, the ACNs in the ACN-CHC/CMC-WPI were more stable and more slower released over time. The nanocomplexes maintained high DPPH and hydroxyl free radical scavenging activities. This study indicated that CHC/CMC-WPI nanocomplexes can improve the thermal stability and slow the release of ACNs added to food products.

[Factors associated with responses of telephone screening interview in a validity and reliability study of telephone interview to assess dietary intake in urban China].

OBJECTIVE: To describe the first phase of a multi-phase study exploring the possibility of conducting telephone dietary intake interviewing in Beijing, Shanghai and Hong Kong in urban China in 2002. METHODS: Three hundred healthy urban Chinese women aged 20 to 49years were sampled by random telephone screening interviews. RESULTS: Examination of the factors associated with their responses to the telephone screening showed that the completion rates differed by day of the week and time of the day. The completion rates were higher onWednesday and Thursday than other weekdays, and higher on Sunday than Saturday at the weekend. There was a trend for the completion rates to peak from 18 :00 to 21:30 during weekday evenings and between 11:00 and 12:00 AM and 19:00 and 20:00 PM during weekends. There was no significant interviewer difference in the completion rates except for one interviewer in Hong Kong, indicating that interviewer performance did not influence completion rates. Of all numbers dialed, 25% of the responding persons refused, with almost all (94.3%) occurring at or near the beginning of the screening interviews, either before or at invitation. Key reasons for refusal included "hung up without any interaction" (35.1%), "not available to participate" (28.6%) or "not interested in survey" (19.0%). Most of the refusals were firm and not possible to reverse.

[Feasibility of telephone screening interview in a validity and reliability study of telephone interview to assess dietary intake in Beijing, Shanghai and Hong Kong].

OBJECTIVE: To understand the feasibility of telephone interviews to achieve recruitment of subjects to assess the validity and reliability of the telephone interview in eliciting dietary intake. METHODS: A multi-phase study was conducted in Beijing, Shanghai and Hong Kong in 2002. RESULTS: Three hundred eligible women aged from 20 to 49 years old were recruited in those cities. In the screening interview, 2462 random telephone numbers were dialed with 95% of dials completed within 5 times of attempts. The average number of dial for the completion was two calls, the rates of completion and refusal conversion were not improved remarkably by the increase of calls although some calling attempts reached 20 times. Regarding the processing of the sampling pools in those three cities, Beijing had a lower efficiency rate but a satisfactory completion rate, Shanghai was good in both indicators, and Hong Kong had a good efficiency rate but lower completion rate. The overall telephone screening interview completion rate was 42%, with Hong Kong having the lowest rate (32%) compared with Beijing and Shanghai (47% and 50%, respectively, P < 0.001). CONCLUSION: The telephone interview method could successfully reach the target of urban Chinese women and earn their cooperation with a satisfactory completion rate.