Navigating the Immune Maze: Pioneering Strategies for Unshackling Cancer Immunotherapy Resistance.

Cancer immunotherapy has ushered in a transformative era in oncology, offering unprecedented promise and opportunities. Despite its remarkable breakthroughs, the field continues to grapple with the persistent challenge of treatment resistance. This resistance not only undermines the widespread efficacy of these pioneering treatments, but also underscores the pressing need for further research. Our exploration into the intricate realm of cancer immunotherapy resistance reveals various mechanisms at play, from primary and secondary resistance to the significant impact of genetic and epigenetic factors, as well as the crucial role of the tumor microenvironment (TME). Furthermore, we stress the importance of devising innovative strategies to counteract this resistance, such as employing combination therapies, tailoring immune checkpoints, and implementing real-time monitoring. By championing these state-of-the-art methods, we anticipate a paradigm that blends personalized healthcare with improved treatment options and is firmly committed to patient welfare. Through a comprehensive and multifaceted approach, we strive to tackle the challenges of resistance, aspiring to elevate cancer immunotherapy as a beacon of hope for patients around the world.

Decoding TROP2 in breast cancer: significance, clinical implications, and therapeutic advancements.

Breast cancer is a heterogeneous disease characterized by distinct molecular subtypes, varied prognoses, and differential treatment responses. Understanding the molecular landscape and identifying therapeutic targets, such as trophoblast cell-surface antigen 2 (TROP2), is vital. TROP2 is notably overexpressed in breast cancer, playing a significant role in tumor growth, invasion, metastasis, and treatment resistance. While significant progress has been made in targeting TROP2 in breast cancer, several challenges and knowledge gaps remain. These challenges include the heterogeneity of TROP2 expression within breast cancer subtypes, resistance to its targeted therapies, potential off-target effects, limited therapeutic agents, and identifying optimal combination treatments. Integrating findings from clinical trials into clinical practice further complicates the landscape. This review article delves deep into TROP2 in breast cancer, highlighting its expression patterns, clinical implications, and therapeutic advancements. By understanding the role of TROP2, we can pave the way for personalized treatments, and transform the landscape of breast cancer care.

Effect of inoculation density of bone marrow mesenchymal stem cells cultured on calcium phosphate cement scaffold on osteogenic differentiation.

BACKGROUND: Calcium phosphate cements (CPCs) are biocompatible materials that have been evaluated as scaffolds in bone tissue engineering. At present, the stem cell density of inoculation on CPC scaffold varies. OBJECTIVE: The aim of this study is to analyze the effect of seeding densities on cell growth and osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) on a calcium phosphate cements (CPCs) scaffold. METHODS: BMMSCs derived from minipigs were seeded onto a CPC scaffold at three densities [1 million/mL (1M), 5 million/mL (5M) and 25 million/mL 25M)], and cultured for osteogenic induction for 1, 4 and 8 days. RESULTS: Well adhered and extended BMMSCs on the CPC scaffold showed significantly different proliferation rates within each seeding density group at different time points (P < 0.05). The number of live cells per unit area in 1M, 5M and 25M increased by 3.5, 3.9 and 2.5 folds respectively. The expression of ALP peaked at 4 days post inoculation with the fold-change being 2.6 and 2.8 times higher in 5M and 25M respectively as compared to 1M. The expression levels of OC, Coll-1 and Runx-2 peaked at 8 days post inoculation. CONCLUSIONS: An optimal seeding density may be more conducive for cell proliferation, differentiation, and extracellular matrix synthesis on scaffolds. We suggest the optimal seeding density should be 5 million/mL.

Breast Cancer Patients: Who Would Benefit from Neoadjuvant Chemotherapies?

Neoadjuvant chemotherapy (NACT) was developed with the aims of shrinking tumors or stopping cancer cells from spreading before surgery. Unfortunately, not all breast cancer patients will benefit from NACT, and thus, patients must weigh the risks and benefits of treatment prior to the initiation of therapy. Currently, the data for predicting the efficacy of NACT is limited. Molecular testing, such as Oncotype DX, MammaPrint, and Curebest 95GC, have been developed to assist which breast cancer patients will benefit from the treatment. Patients with an increased level of Human Leukocyte Antigen-DR isotype, tumor-infiltrating lymphocytes, Fizzy-related protein homolog, and a decreased level of tumor-associated macrophages appear to benefit most from NACT.

Barriers to family intervention to promote child and adolescent vision health: A qualitative study based on community practice in China.

PURPOSE: Child and adolescent myopia is a widespread public health problem worldwide, with high incidence, low age at onset, and severe symptoms. Family management plays a very important role in the prevention and management of myopia in children and adolescents; however, even with knowledge of the health risks of myopia, parents still continue to selectively ignore the importance of visual health, resulting in difficulties with family care related to childhood and adolescent myopia. The purpose of this study was to explore the barriers to family intervention for child and adolescent vision. METHODS: This was a qualitative phenomenological research study that used in-depth semi-structured interviews to explore the experiences of 20 parents whose children had been diagnosed with myopia in Shenzhen, China. Data were analyzed using thematic analysis methods. RESULTS: Three themes emerged: Vision health: neglected care, Going outdoors: the forgotten activity, Education: the top priority. CONCLUSIONS: Our analysis revealed that several factors contributed to barriers to promotion of visual health. One was an incorrect perception of myopia, including the effects of myopia, its non-lethality, and a view that it has minimal impact on daily life. Additionally, when parents faced a conflict between education and vision care, they tended to choose current education and ignore future development of visual problems. PRACTICE IMPLICATIONS: The findings suggest that future family intervention for child and adolescent myopia can be based on the perspective of parental health education, Simultaneously, it should also focus on the balance between education and vision care.

Immunopathological changes, complications, sequelae and immunological memory in COVID-19 patients.

Confirmed SARS-CoV-2-caused disease (COVID-19) cases have reached 275.65 million worldwide. Although the majority of COVID-19 patients present mild to moderate symptoms, some have severe complications including death. We first reviewed the pathogenesis on ACE2, a binding receptor of SARS-CoV-2 expressed in multiple organs, and prevalent multinucleate syncytia in the lung tissues of COVID-19 patients. Then, we evaluated the pathological, immunological changes and sequelae in the major organs. Finally, we reviewed the immunological memory after SARS-CoV-2 infection and vaccination. The binding of SARS-Cov-2 to ACE2 receptor results in reduced ACE2 protein levels, which may lead to elevated susceptibility to inflammation, cell death, organ failure, and potentially severe illness. These damages increase the risk of health problems over a long period, which result in many complications. The complications in multiple organs lead to the increased risk of long-term health problems that require additional attention. A multidisciplinary care team is necessary for further management and recovery of the COVID-19 survivors. Many COVID-19 patients will probably make antibodies against SARS-CoV-2 virus for most of their lives, and the immunity against reinfection would last for 3-61 months.

A novel Cr3+-doped Lu2CaMg2Si3O12 garnet phosphor with broadband emission for near-infrared applications.

Near-infrared (NIR) phosphor-converted light emitting diode (pc-LED) light sources have broad application prospects in environmental science, biomedical and plant growth fields. However, NIR phosphors still suffer from narrowband emission and low thermal stability. Here, we prepared a novel Lu2CaMg2-xSi3O12:xCr3+ (LCMS:xCr3+, x = 0.005-0.06) phosphor with broadband emission by a high-temperature solid state reaction. Under excitation at 450 nm, the emission spectrum of the LCMS:0.05Cr3+ phosphor shows a broadband emission in the range of 650-1000 nm with a large full width at half maximum (FWHM) of 125 nm and an R-line emission of 692 nm. In addition, the LCMS:0.05Cr3+ phosphor has good thermal stability and can maintain 70% emission intensity at 150 °C relative to that at room temperature. The LCMS:0.05Cr3+ phosphor exhibits a high internal quantum efficiency (IQE) of ∼76%. Using this phosphor, a NIR pc-LED with photoelectric efficiencies of 14.8% at 100 mA and 6.0% at 320 mA and NIR output powers of 59.5 mW at 100 mA and 181.0 mW at 320 mA was obtained. The broadband LCMS:0.05Cr3+ phosphor with a NIR emission peaked at 750 nm can serve as a light source for plant cultivation and has superior application prospects in the agriculture field.

Combined use of calcium phosphate cement, mesenchymal stem cells and platelet-rich plasma for bone regeneration in critical-size defect of the femoral condyle in mini-pigs.

Aim: To investigate the outcome of autologous bone marrow mesenchymal stem cells (BMMSCs) and platelet-rich plasma in combination with calcium phosphate cement (CPC) scaffold to reconstruct femoral critical bone defects in mini-pigs. Materials & methods: Scanning electron microscopy, micro-computed tomography evaluation and quantitative histological assessment were used. Results & conclusion: BMMSCs were attached to the CPC scaffold after 7 days of culture and decreased the residual CPC material in each group at 12 weeks compared with 6 weeks. The newly formed bone area was higher in the CPC+SC+P group than in the CPC group at each time point (all p < 0.05). The strategy of CPC combined with BMMSCs and platelet-rich plasma might be an effective method to repair bone defects.

A novel Mn4+ doped oxyfluoride red phosphor for rapid-response backlights display.

An oxyfluoride red phosphor Cs2MoO2F4:Mn4+ was synthesized via a facile co-precipitation route with a certain molecular ratio of CsF and MoO3. X-ray diffraction analysis and its Rietveld refinement reveal that Cs2MoO2F4:Mn4+ crystallized in an orthorhombic structure with the Amam (63) space group. Upon blue light excitation, Cs2MoO2F4:Mn4+ exhibits a series of sharp red emission lines around ∼634 nm and the zero-phonon line (ZPL) is visible at 619 nm. The optimal doping amount of Mn4+ in Cs2MoO2F4 is 1.12%, and the decay curves show a good fit with the single exponential decay model. The fluorescence lifetime of the synthesized phosphors is relatively short and calculated as 3.18 to 2.46 ms, the Mn4+ ions in Cs2MoO2F4 experience a strong crystal field strength with a Dq/B of ∼4.87, and the distinct nephelauxetic ratio ß1 is determined to be ∼1.0226. The thermal quenching mechanism of Mn4+ was also studied. Furthermore, by using the as-synthesized Cs2MoO2F4:Mn4+ phosphor as a red component and ß-SiALON as a green light component, a WLED was fabricated with a high luminous efficacy of 114.70 lm·W-1 and wide color gamut of 109.1% of the National Television Standard Committee (NTSC) value. Hence, the Cs2MoO2F4:Mn4+ phosphor with a short fluorescence lifetime could potentially be an efficient red compensator for application in rapid-response backlight displays.

Factors affecting tumor responders and predictive biomarkers of toxicities in cancer patients treated with immune checkpoint inhibitors.

Cancer immunotherapy has brought a great revolution in the treatment of advanced human cancer. Immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathway (PD-1/PD-L1) have been widely administrated in the past years and demonstrated promising in a variety of malignancies. While some patients show benefit from ICIs, others do not respond or even develop resistance to these therapies. Among the responders, the treatments are consequently accompanied with immune-related adverse effects (irAEs), which are diverse in their effected organs, degree of severity and timing. Some of the toxicities are fatal and result in discontinuance of immunotherapy. The toxicity profile from anti-CTLA-4 to anti-PD-1/PD-L1 immunotherapies is distinct from those caused by conventional anticancer therapies, though their presentation may be similar. In order to better help clinicians recognize, monitor and manage irAEs in a growing population of cancer patients who are receiving ICI therapy, this article summarizes the FDA approved ICIs and focuses on (1) existing toxic evidence related to ICIs, (2) occurrence of irAEs, (3) factors influencing tumor responders treated with ICIs, (4) predictive biomarkers of irAEs, and (5) new potential mechanisms of resistance to ICI therapy.

Designing Micro Bulge Structure with Uniform PS Microspheres for Boosted Dielectric Hydrophobic Blend Films.

In this paper, homogeneous polystyrene (PS) microspheres with controllable sizes of 40 nm, 80 nm, and 120 nm were synthesized by controlling the temperature of solvothermal method. In order to explore the effect of PS microspheres on dielectric-hydrophobic properties of the composite films, the composite films containing polystyrene, Polydimethylsiloxane, and P(VDF-TrFE) with high dielectric and hydrophobicity were successfully prepared by a simple and feasible solution blending method. The dielectric constant and hydrophobicity of composite films were boosted by increasing the mass fraction of PS content and decreasing the size of PS due to the enhanced interfacial polarization and the uniform surface micro bulge structure. Meanwhile, the composite films maintain a low loss tangent. Typically, the dielectric constant with 5 wt.% 40 nm PS reached to 29 at 100Hz, which is 4 times that of PDMS/P(VDF-TrFE) (mass ratio: 2/3). Otherwise, the largest the contact angle of 126° in the same composition was remarkably larger than the pure PDMS/P(VDF-TrFE) (110°). These improved properties have more potential applications in the electric wetting devices.

Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.

One-scan fluorescence emission difference nanoscopy developed with excitation orthogonalized upconversion nanoparticles.

We experimentally realized one-scan fluorescence emission difference nanoscopy (FED) by simultaneously imaging two different color emissions of NaYF4:Er3+@NaYF4@NaYF4:Yb3+/Tm3+ upconversion nanoparticles. Under the irradiation of two synchronized laser beams, a solid 940 nm beam and a hollow 808 nm beam, green emission of Er3+ and blue emission of Tm3+ can be orthogonally generated and collected. After simple subtraction, a resulting super-resolution image featuring 54 nm resolution was obtained. This strategy of excitation orthogonality would greatly improve the imaging speed and the applicability of FED nanoscopy.

[G6PD deficiency among children under 7 years old from Yunnan with unique ethnic minority origin].

OBJECTIVE: To investigate the epidemiological status of glucose-6-phosphate dehydrogenase (G6PD) deficiency among children from Yunnan with unique ethnic origins. METHODS: DNA samples from 11759 children were tested with fluorescent spot test, G6PD/6PGD quantitative ratio assay and hemoglobin electrophoresis. RESULTS: The detection rate of G6PD deficiency was 2.5%, for which boys were significantly greater than girls (3.5% vs. 1.4%, P<0.05). Significant differences were also detected among children from different ethnic groups and different regions. For ethnic Han Chinese, the detection rate was 0.7%, which was lower than the majority of ethnic minorities. By regression analysis, altitude of residence and family history both have significant influence on the calculated rate. CONCLUSION: Occurrence of G6PD deficiency seems to be influenced by gender. It also varies substantially between different ethnic groups as well as regions, e.g., more common in south. It also showed a declining trend after years of diagnosis and intervention. This survey may provide a valuable basis for counseling of G6PD deficiency in Yunnan.

[A survey on anemia among children under 7 years of age from 15 minority ethnic groups in Yunnan].

OBJECTIVE: To investigate the level and distribution characteristics of anemia of the minority ethnic group children in Yunnan. METHOD: The cases with anemia were surveyed from 13 336 samples of 15 minority ethnic groups and Han children in Yunnan by Taking the method of random cluster sampling. RESULT: The prevalence of anemia among the children under 7 years of age of 15 ethnic groups of minority in Yunnan was 13.6%. There are differences among the different ethnic groups (χ(2) = 716.33, P < 0.01), the highest was 26.6% in Jingpo, the lowest was 3.5% in Bai. There were differences among the different regions, the prevalence of anemia was high in the border regions City, the highest was 23.8% in Dehong; the prevalence of anemia was low in inland cities, the lowest was 2.7% in Fugong, and was higher in border areas. The prevalence of anemia was higher in boys (13.6%) than in girls (12.1%). There were differences among the different age in the different ethnic groups (6 months to 1 years old: χ(2) = 70.52, P < 0.01; 1 - 2 years old:χ(2) = 185.86, P < 0.01; 2 - 5 years old: χ(2) = 296.12, P < 0.01; 5 - 6 years old:χ(2) = 107.11, P < 0.01; 6 - 7 years old:χ(2) = 185.02, P < 0.01), the highest was 59.0% of Deang in 1 to 2 years old children. The trend of change was that the highest prevalence was seen in 6 months to 1 year old children, the prevalence gradually declined among older children, but rose again in children 6 years of age or older. CONCLUSION: The prevalence of anemia was 13.6% among the children of 15 ethnic minority under 7 years of age in Yunnan. There were differences among different ethnic groups of minority in different prefectures. There were differences among different ethnic groups of different age groups, but it was highest in 6 months to 1 year old children, it declined among older children, and rose in children 6 years of age or older. The prevalence of anemia was related to the ethnic and geographic factors.

[Epidemiological study of thalasaemia among children in Xishuangbanna, Dehong and Nujiang of Yunnan province].

OBJECTIVE: To investigate the carrier rate of thalasaemia among the children of 10 minority ethnic groups in 3 border states (Xishuangbanna, Dehong and Nujiang) of Yunnan Province. METHODS: A total of 6562 samples of children under 10 years old were analyzed by blood cell automatic analysis and hemoglobin electrophoresis. RESULTS: The overall carrier frequency of thalasaemia was highest (46.2%) in Dehong, and lowest (30.6%) in Nujiang. The carrier frequency of beta-thalasaemia was the highest (40.6%) in Achang, and lowest (2.5%) in Dulong. The carrier frequency of alpha-thalasaemia was the highest (22.1%) in Dai from Xishuangbanna, followed by Dulong (19.1%). CONCLUSION: Thalasaemia carrier rates were high among the children of 10 minority ethnic groups in Yunnan. There were regional differences in their incidences. The results provide a valuable basis for thalasaemia prevention in Yunnan minorities in the three border states.

Self-expanding metallic stents drainage for acute proximal colon obstruction.

AIM: To clarify the usefulness of the self-expanding metallic stents (SEMS) in the management of acute proximal colon obstruction due to colon carcinoma before curative surgery. METHODS: Eighty-one colon (proximal to spleen flex) carcinoma patients (47 males and 34 females, aged 18-94 years, mean = 66.2 years) treated between September 2004 and June 2010 for acute colon obstruction were enrolled to this study, and their clinical and radiological features were reviewed. After a cleaning enema was administered, urgent colonoscopy was performed. Subsequently, endoscopic decompression using SEMS placement was attempted. RESULTS: Endoscopic decompression using SEMS placement was technically successful in 78 (96.3%) of 81 patients. Three patients' symptoms could not be relieved after SEMS placement and emergent operation was performed 1 d later. The site of obstruction was transverse colon in 18 patients, the hepatic flex in 42, and the ascending colon in 21. Following adequate cleansing of the colon, patients' abdominal girth was decreased from 88 ± 3 cm before drainage to 72 ± 6 cm 7 d later, and one-stage surgery after 8 ± 1 d (range, 7-10 d) was performed. No anastomotic leakage or postoperative stenosis occurred after operation. CONCLUSION: SEMS placement is effective and safe in the management of acute proximal colon obstruction due to colon carcinoma, and is considered as a bridged method before curative surgery.

[Epidemiological study on thalassemia among the children of 0 - 7 years old among the six ethnic groups in Xishuangbanna and Dehong of Yunnan province].

OBJECTIVE: To investigate the prevalence rate of thalassemia among children of 0 - 7 years old, from six ethnic groups in Xishuangbanna and Dehong, Yunnan province. METHODS: 4973 blood samples from children under 7 years old were automatically undergone blood cell count, red cell osmotic fragility and hemoglobin electrophoresis testings. RESULTS: The incidence rates of thalassaemia, ß-thalassemia was 37.4%, and α-thalassaemia were 22.6% and 14.7% respectively. The thalassaemia incidence rates were significantly different among age groups but not in gender. The incidence of α-thalassaemia was decreasing along with the increase of age, while the incidence of ß-thalassaemia was increasing along with the increase of age. Xishuangbanna had the higher incidence than in Dehong and the differences were significant between counties, The incidence of thalassemia of Mengla ranked the first (52.2%) in Xishuangbanna, The differences between different regions and different nationalities were significant, with ß-thalassemia of Achang ranked the first (40.6%), The incidence of α-thalassemia among Han ranked the first as 45.5% while α-thalassaemia and ß-thalassemia were different in regions. α-thalassaemia and ß-thalassemia were significantly different between different ethnic people in the same regions. Multiple factor analysis showed that region seemed to be a risk factor and the mother's ethnicity was a protective factor and dependent variable on thalassaemia. CONCLUSION: The incidence of thalassaemia in Yunnan Xishuangbanna and Dehong was high among children under the age of 7 and were related to ethnic and regional differences in the areas. Specific genes were proliferated along with the extension of time. Our data provided valuable information on prevention and genetic studies on thalassaemia in the minorities of Xishuangbanna and Dehong in Yunnan province.

Rectal stenosis after procedures for prolapse and hemorrhoids (PPH)--a report from China.

OBJECTIVES: After it was introduced in China in 2000, the surgical procedure for prolapse and hemorrhoids (PPH) has become a widely accepted for third- and fourth-degree hemorrhoids. Stenosis of the lower rectum is one of the delayed complications. In order to evaluate this specific problem following PPH, we reviewed our data with special reference to potential predictive factors or stenotic events. METHODS: A retrospective analysis of 554 consecutive patients that underwent PPH from July 2000 to December 2004 was performed. Only patients with follow-up check were evaluated; therefore 65 patients (11.7%) Hwere lost to follow-up, and the analysis therefore includes 489 patients with a mean follow-up of 324 days (+/-18 days). For statistical analysis, the groups with and without stenosis were evaluated using the chi-square test; using the Kaplan-Meier statistic, the actuarial incidence for rectal stenosis was plotted. RESULTS: Rectal stenosis was observed in 12 patients (2.5%) in whom the median time to stenosis was 125 (89 approximately 134) days. All patients complained of obstructive defecation and underwent strictureplasty with electrocautery or balloon dilation through colonoscopy. A statistical analysis revealed that two factors were significantly more prevalent among patients with stenosis: prior sclerosis therapy for hemorrhoids (P=0.02) and severe postoperative pain (P=0.003). Other factors, such as gender (P=0.32), prior surgery for hemorrhoids (P=0.11), histological evidence of squamous skin (P=0.77) or revision (P=0.53) showed no significance. CONCLUSIONS: Rectal stenosis is an uncommon event after PPH. Early stenosis will occur within the first 4 months after surgery. In most cases, the stenosis can be cured through colonoscopy surgery. Predictive factors for stenosis are previous sclerosis therapy for hemorrhoids and severe postoperative pain.