BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Objective To investigate the association of estimated glucose disposal rate(eGDR)with metabolic dysfunction-associated liver steatosis and fibrosis,and to analyze the difference of the association in different population.Methods A total of 10,549 participants from 2017 to 2020 in National Health and Nutrition Examination Survey(NHANES)database who underwent vibration-controlled transient elastography(VCTE)were included.eGDR was calculated based on waist circ-umference,hypertension,and glycated hemoglobin(HbA1c).The controlled attenuation parameter(CAP)≥248 dB/m was used as diagnostic criterion for liver steatosis,and liver stiffness measure-ment(LSM)≥ 8.2 kPa was used as criterion for liver fibrosis.Multivariable Logistic regression a-nalysis was conducted to assess the relationship between eGDR and liver steatosis and fibrosis,with subgroup analysis and interaction tests performed.Results After adjusting for confounding factors,eGDR level was significantly negatively associated with the risks of both liver steatosis and fibrosis.The participants were divided into tertiles based on eGDR levels(Q1,Q2,Q3).Compared with the Q1 group,the risk ratios for liver steatosis in the Q2 and Q3 groups were 0.485(95％CI,0.394 to 0.597)and 0.286(95％CI,0.239 to 0.343),respectively(P＜0.001);the risk ratios for liver fibrosis were 0.457(95％CI,0.363 to 0.576)and 0.162(95％CI,0.100 to 0.263),respective-ly(P＜0.001).Subgroup analysis showed that the negative association between eGDR and liver steatosis differed among populations of different ages and smoking statuses,with statistically signifi-cant differences in interaction tests(P for interaction＜0.001);similarly,the negative association between eGDR and liver fibrosis differed among populations with different levels of physical activity,with statistically significant differences in interaction tests(P for interaction＜0.001).The associa-tions of eGDR levels with liver steatosis and fibrosis remained stable(P for interaction＞0.05).Conclusion eGDR levels are closely associated with the risks of liver steatosis and fibrosis and can serve as an effective indicator for assessing liver metabolic abnormalities.This finding provides new insights into early screening,risk stratification,and prognosis assessment for liver steatosis and fibrosis.

This paper discusses the mechanism of acupuncture for diabetes mellitus from the perspective of molecular biology, aiming to reveal the potential rules of restoring the balance in the body and fighting against diabetes mellitus (DM). By searching the basic research literature of acupuncture treatment for DM, it is found that the molecular biological mechanism of acupuncture treatment for DM is closely related to the regulation of insulin signaling pathway, the modulation of inflammatory response, the protection and regeneration of islet β-cells, fat metabolism and energy balance. It points out that there are few studies of acupuncture on the type 1 diabetes mellitus and the large-scale randomized controlled trials, as well as the studies on the upstream regulation mechanism, the specific cellular molecules and the interaction mechanism of various molecules. It needs to deepen the multi-level, multi-target and multi-dimensional exploration on the molecular biological mechanism of acupuncture for diabetes mellitus.
Humans ; Acupuncture Therapy ; Diabetes Mellitus/genetics* ; Animals ; Insulin/metabolism* ; Signal Transduction

Small for gestational age (SGA) infants are more likely to experience neurocognitive impairments compared to appropriate for gestational age (AGA) infants. This paper reviews recent research on the neurocognitive development of SGA children. SGA can lead to a "brain-sparing effect" due to growth restriction, which may affect cerebral blood flow and brain structure. However, this does not guarantee normal brain development. Restrictive blood flow can result in changes in brain structure, such as reduced total white matter and gray matter volume in various brain regions, including the cerebral cortex, hippocampus and cerebellum, ultimately leading to decreased head circumference. SGA children also exhibit lower scores in all neurocognitive domains, including intelligence, attention, memory, and executive function. This may result in poor academic performance and an increased risk of social, behavioral, and neurological problems, such as cerebral palsy, epilepsy, visual and hearing impairments, as well as comorbidities like attention deficit hyperactivity disorder(ADHD), autism spectrum disorder(ASD), anxiety, depression, and schizophrenia. Several risk factors for SGA-related neurocognitive impairments have been identified, including gestational hypertension, abnormal gestational weight, smoking, and catch-up growth. Studies have shown that the best interventions to improve cognitive dysplasia include nutrient supplementation, continued breastfeeding, high-quality education, and appropriate early intervention (responsive parenting) are effective in improving cognitive outcomes for SGA children.

A 38-year-old female patient with recurrence of breast cancer accompanied by liver metastasis received intravenous infusion of sintilimab 200 mg on the first day and 21 days was a cycle. Before the immunotherapy, her function of liver, kidney, and thyroid was normal. Three days after the medication, the patient developed rash and itching on skin of waist. After that, diffuse erythema and desquamation appeared on skin of her whole body and blisters appeared on both upper limbs and back. At the same time, she developed blurred vision, increased eye secretions, and foreign-body sensation. Laboratory tests showed alanine aminotransferase (ALT) 123 U/L, aspartate aminotransferase (AST) 342 UL, γ-Glutamyltransferase (γ-GT) 907 U/L, alkaline phosphatase (ALP) 424 U/L, serum creatinine (Scr) 95.6 μmol/L, uric acid 691.0 μmol/L, and thyroid-stimulating hormone (TSH) 20.87 mU/L. She was diagnosed with rash, hypothyroidism, kidney injury, conjunctivitis, and liver injury, which were considered to be associated with sintilimab. After 16 days of symptomatic treatments such as IV infusions of methylprednisolone sodium succinate for injection and magnesium isoglycyrrhizinate injection, oral administration of levothyroxine sodium and Haikun Shenxi capsules (海昆肾喜胶囊), levofloxacin eye drops, and skin care, her rash was subsided, blisters were absorbed, and the discomfort in the eyes disappeared. Laboratory tests showed ALT 111 UL, AST 122 U/L, γ-GT 1 430 U/L, ALP 321 U/L, Scr 56.0 μmol/L, uric acid 243.0 μmol/L, and TSH 13.60 mU/L.

A 38-year-old female patient with recurrence of breast cancer accompanied by liver metastasis received intravenous infusion of sintilimab 200 mg on the first day and 21 days was a cycle. Before the immunotherapy, her function of liver, kidney, and thyroid was normal. Three days after the medication, the patient developed rash and itching on skin of waist. After that, diffuse erythema and desquamation appeared on skin of her whole body and blisters appeared on both upper limbs and back. At the same time, she developed blurred vision, increased eye secretions, and foreign-body sensation. Laboratory tests showed alanine aminotransferase (ALT) 123 U/L, aspartate aminotransferase (AST) 342 UL, γ-Glutamyltransferase (γ-GT) 907 U/L, alkaline phosphatase (ALP) 424 U/L, serum creatinine (Scr) 95.6 μmol/L, uric acid 691.0 μmol/L, and thyroid-stimulating hormone (TSH) 20.87 mU/L. She was diagnosed with rash, hypothyroidism, kidney injury, conjunctivitis, and liver injury, which were considered to be associated with sintilimab. After 16 days of symptomatic treatments such as IV infusions of methylprednisolone sodium succinate for injection and magnesium isoglycyrrhizinate injection, oral administration of levothyroxine sodium and Haikun Shenxi capsules (海昆肾喜胶囊), levofloxacin eye drops, and skin care, her rash was subsided, blisters were absorbed, and the discomfort in the eyes disappeared. Laboratory tests showed ALT 111 UL, AST 122 U/L, γ-GT 1 430 U/L, ALP 321 U/L, Scr 56.0 μmol/L, uric acid 243.0 μmol/L, and TSH 13.60 mU/L.

Although current direct anti-hepatitis B virus (HBV) drugs have good effects in controlling viral replication and limiting the progression to liver cirrhosis, there is still a long way to go in the treatment of chronic hepatitis B (CHB). Immune tolerance and immune dysfunction may be the two most important immunopathogenic factors. With reference to the development of new strategies and new drugs for anti-HBV immunotherapy and the latest research findings around the world, this article reviews the research advances in immunotherapy for CHB in recent years.

Objective To investigate the molecular biological mechanism of deposition of triglyceride(TG)in hepatocytes in alcoholic fatty liver disease(AFLD)and the pathogenesis of this condition by detecting the contents of serum tumor necrosis fac-tor-α(TNF-α),liver triglyceride(TG),peroxisome proliferator-activated receptorα(PPARα)and acyl-CoA oxidase(Acox1)mR-NAs,and liver PPARαprotein after intervention with bezafibrate,a PPARαagonist.Methods Sixty Wistar rats were randomly divided into three groups:control group(n=20),AFLD group(n=20),and bezafibrate group(n=20).Animals in control group were given distilled water by gavage once a day for 8 weeks.Those in AFLD group were given ethanol and fish oil(2.5 mL/kg) by gavage daily for the same period of time.In bezafibrate group,rats were treated by gavage with ethanol and fish oil(2.5 mL/kg)for the first 4 weeks and then with bezafibrate(100 mg/kg)for another 4 weeks.TG in the liver was measured by colorimet-ric method,serum TNF-αlevels by enzyme linked immunoabsorbent assay (ELISA),the mRNA expression of PPARαand Acox1 in hepatocytes by reverse transcription polymerase chain reaction(RT-PCR)and the expression of PPARαprotein in hep-atocytes by Western blot.Results A significant increase in TG[AFLD group(0.72±0.09)mmol/L vs.control group(0.28± 0.07)mmol/L,P<0.01]and TNF-α[AFLD group(3.01±0.31)ng/mL vs.control group(1.07±0.28)ng/mL,P<0.01]was found in AFLD group when compared with control group.After bezafibrate intervention,the contents of liver TG and serum TNF-αwere significantly decreased.The mRNA expression of PPARα[AFLD group(0.22±0.08)vs.control group(0.68± 0.13),P<0.01]and Acox1[AFLD group(0.43±0.12)vs.control group(1.14±0.21),P<0.01]was suppressed in AFLD group,which was significantly reversed by bezafibrate treatment[bezafibrate group(0.59±0.13)for PPARαmRNA vs.AFLD group,P<0.01;bezafibrate group(0.83±0.17)for Acox1 mRNA vs.AFLD group,P<0.01].The expression of PPARαpro-tein in hepatocyts was also found to decrease in AFLD group[AFLD group(0.19±0.07)vs.control group(0.48±0.11),P<0.01].After bezafibrate intervention,it was profoundly increased.Conclusion The down-expression of PPARαand Acox1 in the liver of rats with AFLD may suppress the fatty acid metabolism and lead to the TG deposition in the liver.The increase in serum TNF-αcontents also contributes to the development of AFL.Bezafibrate can prevent and treat AFL by activating PPARα,increasing the expression of PPARαand Acox1 ,promoting the metabolism of fatty acids,decreasing the TG deposition and the serum TNF-αcontents.

Inflammasome is a multi-protein complex which plays an important role in innate immune defense,and can adjust the activation of caspase-1 and promote the production of cytokines. NLRP3 is an important member of inflammasome Nod-like receptor(NLR)family,and its activation and expression occur mainly in macrophages and dendritic cells. NLRP3 can sense the pathogen associated molecular patterns(PAMPs)and damage associated molecular patterns(DAMPs)and initiate the inherent immune response,which plays an important role in the pathogenesis of autoimmune diseases. This article reviewed the advances in study on NLRP3 in autoimmune diseases.

Good doctor-patient communication is the most effective way to build a harmonious doctor-patient relationship and reduce medical disputes, where the communication skill is the key. In communication with the hospitalized patients, it should pay attention to the communication object choice;the choice of the communicator;communication time, location and the form; pay attention to the communication protocol; using a comprehensible language communication;stand in the perspective of patients in order to enhance the doctor-patient trust and im-prove the doctor-patient relationship.