Objective: To report the antibody identification, blood management during pregnancy and the monitoring process of fetal hemolytic disease of fetus and newborn (HDFN) in a pregnant woman with a history of blood transfusion and pregnancy who developed anti-Jr . Methods: Saline tube technique and anti-human globulin technique were used for maternal blood typing, unexpected antibody screening and identification, as well as for determining antibody titer and IgG subclasses. PCR-SSP was employed for genotyping of 18 blood group systems. Next-generation sequencing (NGS) was utilized for gene sequencing of 38 blood group systems. Sanger sequencing was applied to verify rare blood group mutations detected by NGS and to investigate the corresponding rare blood group genes in family members. Blood preparation was achieved through anemia management in prenatal clinics and autologous blood collection during pregnancy. The newborn underwent the three primary tests for HDFN and plasma IgG subclass testing. Results: The pregnant woman's blood type was B, RhD positive, with a positive unexpected antibody screen, and the antibody identification pattern was consistent with a high-frequency antigen antibody. Gene sequencing revealed a homozygous ABCG2 c.376C>T mutation in the woman, resulting in the Jr(a-) phenotype, and anti-Jr antibody was present in her plasma. No compatible Jr(a-) blood was found among family members. The maternal anti-Jr IgG titer remained stable at 256 during pregnancy, with no detectable IgG1 or IgG3 subclasses against the Jr antigen. A total of 800 mL of autologous blood was collected in two stages during pregnancy. The newborn was B, RhD positive, Jr(a+), with a positive unexpected antibody screen (anti-Jr ). IgG subclass typing detected no IgG1 or IgG3. The direct antiglobulin test was positive, while the acid elution test was negative. Conclusion: The combination of serology and blood group genetic analysis provides a diagnostic basis for identifying antibodies to high-frequency antigens. Managing perinatal anemia and implementing staged autologous blood storage can secure blood supply for the perioperative period. IgG antibody subclass typing offers a reference for clinical assessment and prevention of HDFN.

Objective To systematically analyze the spatiotemporal distribution characteristics and epidemiological trends of tracheal, bronchus, and lung cancer (TBL) disease burden attributed to air pollution globally and in China and the United States from 1990 to 2021, and to assess the patterns of disease burden changes from 2022 to 2031 based on predictive models, providing a scientific basis for formulating targeted TBL prevention and control strategies. Methods Based on the Global Burden of Disease (GBD) 2021 database, we analyzed the disease burden data of TBL attributed to air pollution globally and in China and the United States from 1990 to 2021. R Studio 4.3.2 software was used to analyze the corresponding trends and the Bayesian age-period-cohort (BAPC) prediction model was used to predict the status of the disease burden of TBL attributed to air pollution in the world and in China and the United States from 2022 to 2031. Results In 2021, China had the highest number of deaths and disability-adjusted life years attributed to air pollution (211 400 patients and 4.8947 million person-years), followed by the United States (6 000 patients and 124 300 person-years). The age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) of TBL due to air pollution in the world and in China and the United States showed a decreasing trend. From 1990 to 2021, the ASMR and ASDR of TBL in China due to air pollution were much higher than those in the United States and the global average. In terms of gender, from 1990 to 2021, the disease burden of male patients with TBL attributed to air pollution was much higher than that of female patients. The BAPC prediction model showed that from 2022 to 2031, the ASMR and ASDR of TBL attributed to air pollution showed an upward trend globally, while they showed a downward trend in China and the United States. Conclusion Over the past 30 years, the air pollution-related TBL disease burden in the world and in China and the United States has continued to decline, but China's disease burden is still significantly higher than the global average. The disease burden in men far exceeds that in women, with men and the population aged ≥50 years being high-risk groups. In the future, the global disease trend may reverse and rise, while China and the United States are expected to continuously decline. However, precise prevention and control for high-risk groups remains a key challenge.

ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

Ulcerative colitis （UC） is a chronic， non-specific intestinal inflammatory disease. Its pathogenesis is complex， involving interactions among genetic， immune， and environmental factors， and remains incompletely elucidated. Mitochondrial damage can trigger the abnormal release of mitochondrial damage-associated molecular patterns （mtDAMPs）， activating inflammatory pathways and thereby exacerbating the inflammatory response in UC. Mitophagy， a core mitochondrial quality control mechanism， can clear damaged mitochondria and effectively reduce the abnormal release of mtDAMPs and the accumulation of harmful substances， thereby mitigating inflammatory damage resulting from mitochondrial dysfunction. Mitophagy plays a crucial role in maintaining the integrity of the intestinal epithelial barrier function and in the prevention and intervention of UC. Notably， the function of the spleen governing transportation and transformation in traditional Chinese medicine shares similarities with the role of mitochondria in energy transformation and substance metabolism. Furthermore， the pathological state of the spleen failing in transportation and transformation may be related to mitochondrial dysfunction， while the pathogenic characteristics of "endogenous turbid pathogen" align with the inflammatory cascade responses triggered by abnormal release of mtDAMPs. Based on this theoretical correlation， this paper aims to explore the correlation between the traditional Chinese medicine theory of "spleen dysfunction in essence distribution leading to endogenous turbid pathogens" and mitophagy. Using the correlation as an entry point， the potential role of mitophagy in the pathogenesis of UC was elucidated. Additionally， by considering the epidemiological characteristics of UC in the Southwest region of China， a new thinking for the treatment of UC from the perspective of turbid pathogens was proposed based on the "fortifying the spleen and resolving turbidity" method to provide theoretical support and research enlightenment for further exploring the prevention and treatment of UC with traditional Chinese medicine.

ObjectiveTo explore the mechanism by which Qifu Lizhong decoction restores intestinal mucosal barrier function in ulcerative colitis （UC） by regulating the myosin light chain kinase （MLCK）/phosphorylated myosin light chain （p-MLC） signaling pathway. MethodsA rat model of UC with spleen-kidney Yang deficiency syndrome and an in vitro intestinal barrier injury model were established. In vivo experiments were conducted to evaluate the body weight， disease activity index （DAI） scores， and changes in colonic pathological morphology in each group of rats. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and myeloperoxidase （MPO）. Transmission electron microscopy （TEM） was employed to observe the morphology and structure of tight junctions （TJ） in rat colonic epithelium. In vitro experiments were conducted to observe the morphology of F-actin in human colon adenocarcinoma cell line-2（Caco-2） cells by phalloidin staining. Combining both in vivo and in vitro approaches， immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were applied to detect the expression and phosphorylation levels of TJ proteins ［zonula occludens-1 （ZO-1）， Occludin， Claudin-1］ as well as key proteins in the MLCK/p-MLC signaling pathway. ResultsIn vivo experiments demonstrated that， compared with the normal group， the model group exhibited significant body weight loss， elevated DAI scores and histopathological scores （P<0.01）， increased colonic TNF-α， IL-1β， and MPO levels （P<0.01）. TJ structures were disrupted， and the expression of ZO-1， Occludin， and Claudin-1 was significantly reduced （P<0.05， P<0.01）. The protein expression levels of myosin light chain （MLC）， MLCK， phosphorylated （p）-MLC， and p-MLCK significantly increased （P<0.01）. Compared with the model group， all Qifu Lizhong decoction dose groups exhibited increased body weight， as well as significantly decreased DAI scores and histopathological scores （P<0.05， P<0.01）. The colonic levels of MPO， TNF-α， and IL-1β were significantly reduced （P<0.05， P<0.01）. In the Qifu Lizhong decoction + inhibitor group， the expression of TJ proteins ZO-1， Occludin， and Claudin-1 significantly increased （P<0.01）， while the protein expression levels of MLC， MLCK， p-MLC， and p-MLCK were significantly reduced （P<0.01）. In vitro experiment results showed that， compared with the normal group， the TNF-α group exhibited disordered cytoskeletal architecture， weakened fluorescence signals of ZO-1， Occludin， and Claudin-1， and significantly elevated protein expression levels of MLC， MLCK， p-MLC， and p-MLCK （P<0.01）. Compared with the TNF-α group， the Qifu Lizhong decoction + inhibitor group restored the ordered arrangement of the F-actin cytoskeleton， normalized the expression and localization of TJ proteins ZO-1， Occludin， and Claudin-1， and significantly decreased the protein expression levels of MLC， MLCK， p-MLC， and p-MLCK （P<0.01）. ConclusionQifu Lizhong decoction may exert its therapeutic effects on UC by inhibiting the MLCK/p-MLC signaling pathway， thereby stabilizing TJ structure and repairing intestinal barrier integrity.

AIM: To explore the control effects of wearing orthokeratology lens for 1 a on adolescent myopia patients with different diopters.METHODS: Prospective non-randomized controlled study. A total of 120 adolescent myopic patients(224 eyes), with an average age of 11.00±2.08 years old, who were fitted with orthokeratology lenses in the optometry department of our hospital from November 2022 to May 2023 were collected. There were 3 groups according to the spherical equivalent, including 86 eyes in the group of -0.50--2.00 D, 99 eyes in the group -2.25--4.00 D, and 39 eyes in group -4.25--6.00 D. Patients were followed up for 1 a to observe the changes of uncorrected visual acuity, axial length, corneal curvature, corneal central thickness and corneal endothelial cells density in the three groups after wearing lens for 1 a.RESULTS:A total of 113 cases(212 eyes)were followed up for 1 a, including 82 eyes in the group of -0.50--2.00 D, 95 eyes in the group of -2.25--4.00 D, and 35 eyes in the group of -4.25--6.00 D. There was no statistical difference in corneal central thickness and corneal endothelial cell density among the three groups of patients after wearing lens for 1 a(all P>0.05). Uncorrected visual acuity was significantly improved, and flat kerotometry(FK)and steep kerotometry(SK)were significantly flatter(both P<0.01). Furthermore, the growth of axial length in the three groups of patients after wearing lens for 1 a was 0.21±0.26, 0.13±0.21 and 0.09±0.10 mm, respectively(P<0.05). There were differences between the -0.50--2.00 D group and the -2.25--4.00 D group and -4.25--6.00 D group(P=0.028, 0.010), and there were no differences between the -2.25--4.00 D group and the -4.25--6.00 D group(P=0.344).CONCLUSION:It is safe and effective for young myopia patients to wear orthokeratology lenses, which can prevent the non-benign growth of the axial length and effectively delay the development of myopia, and the myopia control effect is better especially for myopia patients of above -2.0 D.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

BACKGROUND: Premature menopause, defined as natural menopause before age 40, is associated with diminished ovarian reserve. Despite growing concerns regarding environmental pollutants, no large-scale population-based studies have systematically examined the association between urinary polycyclic aromatic hydrocarbon metabolites (UPAHMs) and premature menopause. METHODS: This cross-sectional study analyzed 2001-2020 NHANES data, including urinary levels of six PAH metabolites: 1-naphthol (1-NAP), 2-naphthol (2-NAP), 3-fluorene (3-FLU), 2-fluorene (2-FLU), 1-phenanthrene (1-PHE), and 1-pyrene (1-PYR). Premature menopause was self-reported as natural menopause occurring before age 40. Multivariable logistic regression assessed UPAHMs' association with premature menopause, with restricted cubic splines (RCS) evaluating nonlinear trends. Subgroup analyses examined demographic interactions. RESULTS: Among 2,565 participants, 662 reported premature menopause. Multivariable logistic regression showed significant associations between elevated urinary levels of 1-NAP (OR: 1.01, 95% CI: 1.00-1.02, P = 0.02), 2-NAP (OR: 1.01, 95% CI: 1.00-1.02, P = 0.02), and 3-FLU (OR: 1.03, 95% CI: 1.01-1.05, P = 0.01) and increased risk of premature menopause. RCS analysis revealed significant nonlinear relationships for 2-NAP, 3-FLU, 2-FLU, 1-PHE, and 1-PYR with premature menopause risk. White participants showed greater susceptibility to UPAHMs. CONCLUSION Elevated UPAHMs, particularly 1-NAP, 2-NAP, and 3-FLU, were linked to higher premature menopause risk, with nonlinear trends observed. White individuals demonstrated greater vulnerability, emphasizing the need for targeted interventions to reduce PAH exposure.
Humans ; Female ; Cross-Sectional Studies ; United States/epidemiology* ; Polycyclic Aromatic Hydrocarbons/urine* ; Adult ; Middle Aged ; Environmental Pollutants/urine* ; Nutrition Surveys ; Menopause, Premature/urine* ; Young Adult ; Environmental Exposure