OBJECTIVE To comparatively analyze tumor staging versus clinical staging in reimbursement scope restrictions under medical insurance for antineoplastic agents in order to better implement the medicare drug payment policy. METHODS Antineoplastic agents included in the National Basic Medical Insurance， Workers’ Compensation Insurance and Maternity Insurance Drug Catalogue （2024） （hereinafter referred to as the “Medical Insurance Catalog”） were used as research subject to compile and analyze reimbursement scope restrictions regarding tumor staging. By consulting clinical diagnosis and treatment guidelines and relevant literature， the tumor staging in reimbursement scope restrictions of the Medical Insurance Catalog was mapped and compared with clinical staging. RESULTS & CONCLUSIONS A total of 89 antineoplastic agents’ medical insurance payments had tumor staging. Among these， there were 86 western drugs （including 17 ordinary western drugs， 68 negotiated drugs， and 1 competitive drug） and 3 Chinese patent medicines （including 1 ordinary Chinese patent medicine and 2 negotiated drugs）. Non-small cell lung cancer involved the most restricted payment drugs， with 36 drugs. The tumor staging in reimbursement scope restrictions was mostly “metastatic” and “locally advanced”， involving 67 and 48 drugs respectively. Tumor staging in most reimbursement scope restrictions could correspond to the clinical staging of the tumor. However， mid-advanced esophageal cancer， unresectable gastrointestinal stromal tumors， unresectable locally advanced neuroendocrine tumors， locally advanced basal cell carcinoma， and unresectable neurofibromatosis type Ⅰ did not have a corresponding clinical staging mentioned in authoritative guidelines or high-quality clinical studies and need to be determined by the clinic according to the actual situation of the patient. Therefore， it is recommended that the interpretation of tumor staging in reimbursement scope restrictions should be accurately defined and standardized， so as to improve the accuracy of the drug payment policy in the actual implementation process.

OBJECTIVE To investigate ameliorative effects and mechanisms of two probiotics （Bacillus subtilis， Lactobacillus acidophilus） combined with Aurantii Fructus Immaturus （AFI） on functional dyspepsia （FD） in rats. METHODS Rats were randomly divided into blank group， model group， positive control group （domperidone group， 2.7 mg/kg）， AFI group （9 g/kg）， L. acidophilus group （5×107 cfu/kg）， B. subtilis group （5×107 cfu/kg）， L. acidophilus+ AFI group （L. acidophilus 5×107 cfu/kg+ AFI 9 g/kg）， and B. subtilis+AFI group （B. subtilis 5×107 cfu/kg+AFI 9 g/kg）， with 8 rats in each group. Except for the blank group， FD model was established by tail-clamping stimulation+hunger and satiety disorder+swimming exhaustion in other groups. After modeling， each group was given the corresponding drug/probiotic suspensions/physiological saline intragastrically， once a day， for 14 consecutive days. After the last medication， gastric emptying rate and the rate of propulsion of the small intestine in rats were measured； the levels of brain-gut peptide-related indicators [gastrin （GAS）， substance P （SP）， vasoactive intestinal peptide （VIP）， somatostatin （SS） and cholecystokinin （CCK）] in the serum of rats were measured. The pathological morphology of the gastric antrum tissue and duodenal tissue was observed. Cecal contents from the rats were collected for gut microbiota sequencing analysis. The protein expression levels of tyrosine kinase receptor c-Kit and stem cell factor （SCF） in the gastric antrum tissue， as well as Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor κB （NF-κB） in the duodenal tissue of the rats were detected. RESULTS Compared with the blank group， model group showed significantly lower gastric emptying rate， small intestinal propulsion rate， serum levels of GAS and SP， relative abundance of Firmicutes， Ace， Chao and Sobs indexes of the gut microbiota， and protein levels of SCF and c-Kit in gastric antrum （P＜0.05）， while serum levels of VIP， SS and CCK， relative abundance of Bacteroidetes， as well as protein expressions of TLR4， MyD88， and NF-κB， were significantly higher （P＜0.05）. The histological structure JZYC23S53） of the gastric antrum tissue appeared basically normal； however， abnormalities were observed in the duodenal structure， with a significant infiltration of inflammatory cells visible. Compared with the model group， all treatment groups significantly modulated most of the above indexes （P＜0.05）. The histological structure of the gastric antrum tissue was normal. Except for the B. subtilis group and the B. subtilis+AFI group， the pathological states of the duodenum in the remaining rats gradually recovered. Compared with each single drug group， most of above indexes in rats from each combination group showed further improvement （P＜0.05）. CONCLUSIONS The combination of AFI with two probiotics can improve gastrointestinal motility in FD rats， and the effect is superior to that of using the drugs alone. The specific underlying mechanisms may be related to the activation of the SCF/c-Kit signaling pathway and the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the relationship between the non-fasting triglyceride and glucose （TyG） index and hyperglycemia in pregnancy during the third trimester in high altitudes. MethodsThis study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region， from January 2023 to April 2025. The non-fasting TyG index was calculated from non-fasting triglyceride （TG） and random plasma glucose （PG）. Based on the tertiles of the non-fasting TyG index values， the individuals were split into three groups （corresponding to non-fasting TyG index of 8.89 and 9.21， respectively）. The baseline clinical characteristics， lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups. Statistical analyses were performed using ANOVA， Kruskal-Wallis H test， Chi-square test， or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting. ResultsA total of 774 Tibetan singleton pregnant women were included， with a average age of 27.3 ± 6.1 years， a pre-delivery body mass index （Pre-BMI） of （25.2±2.3）kg/m² ， a proportion of 26.7% （207/774） primigravid women， the mean non-fasting TyG index was 9.1 ± 0.4。Thirty pregnant women were diagnosed with hyperglycemia in pregnancy， with a detection rate of 3.9% （30/774）. Statistically significant differences in serum total cholesterol （TC）， TG， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） levels were identified when comparing different non-fasting TyG groups （all P values <0.05）. Subsequent trend test analysis indicated that the levels of TC， TG， LDL-C， and PG gradually increased with elevated the non-fasting TyG index （ F_{trend TC}=95.61， P<0.001； F_{trend TG}=1 051.91， P<0.001； F_{trend LDL-C} = 97.20， P < 0.001； F_{trend TG}=195.20； P<0.001）. After adjustment for maternal age， pre-delivery BMI， altitude， TC， LDL-C， and HDL-C， multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy （Model 1： OR=2.72， 95% CI： 1.13-6.53， P=0.026； Model 2： OR=2.56， 95% CI： 1.01-6.50， P=0.048； Model 3： OR=2.72， 95% CI： 1.06-6.97， P=0.037； Model 4： OR=4.02， 95% CI： 1.42-11.40， P=0.009） and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index， however， this association did not statistical significance （P _trend >0.05）. Curve fitting by restricted cubic splines （RCS） were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy， and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy （P _{for non-linear} = 0.515）. ConclusionNon-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.

Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade (ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified; some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration (FDA) for clinical treatment. However, limited responses and immune-related adverse events (irAEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasms/drug therapy* ; Immunotherapy/methods* ; Animals

The pursuit of healthy aging has long rendered aging and senescence captivating. Age-related ailments, such as cardiovascular diseases, diabetes, and neurodegenerative disorders, pose significant threats to individuals. Recent studies have shed light on the intricate mechanisms encompassing genetics, epigenetics, transcriptomics, and metabolomics in the processes of senescence and aging, as well as the establishment of age-related pathologies. Amidst these underlying mechanisms governing aging and related pathology metabolism assumes a pivotal role that holds promise for intervention and therapeutics. The advancements in metabolomics techniques and analysis methods have significantly propelled the study of senescence and aging, particularly with the aid of multiscale metabolomics which has facilitated the discovery of metabolic markers and therapeutic potentials. This review provides an overview of senescence and aging, emphasizing the crucial role metabolism plays in the aging process as well as age-related diseases.
Humans ; Aging/metabolism* ; Metabolomics/methods* ; Neurodegenerative Diseases/metabolism* ; Cardiovascular Diseases/metabolism*

Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

ObjectiveTo detect the flexibility differences of Plasmodium berghei K173 （PbK173）-infected red blood cells with varying degrees of sensitivity to artemisinin-based drugs and to preliminarily explore the underlying mechanisms of the differences. MethodA total of 102 specific-pathogen-free （SPF） male C57BL/6 mice were randomly divided into three groups， with 30 mice each in the control group and PbK173-resistant （PbK173-R） group， and 42 mice in the PbK173-sensitive （PbK173-S） group. Except for the control group， the rest groups were vaccinated with 1×10⁷ PbK173-S/PbK173-R infected red blood cells to establish a mouse malaria model. During the administration and recovery periods （control group， PbK173-R/PbK173-S）， dihydroartemisinin （DHA， 40 mg·kg^-1） and malaridine （MD， 6 mg·kg^-1） were administered continuously for four days. Peripheral blood was taken from the PbK173-S/PbK173-R groups with an infection rate equal to or greater than 20%. Peripheral blood and each organ were taken on the first day at the end of administration （dosing period） and on the fifth day at the end of administration （recovery period）， and blood parameters and organ indices of each group were examined. The osmotic fragility of peripheral blood red blood cells in each group was detected using the red blood cell osmotic fragility test. Western blot was applied to determine the levels of Piezo1 and Band3 proteins in the red blood cell membrane. ResultDuring the administration and recovery periods， there were no significant differences between the PbK173-S MD group and the DHA group. During the administration period， there were no significant differences in hematological parameters between PbK173-S and PbK173-R in the MD group. However， during the recovery period， the red blood cell count， hemoglobin concentration and hematocrit of the PbK173-R group were significantly higher than those of the PbK173-S group （P<0.05） in the MD group. Compared with that of the control group， the osmotic fragility of the PbK173-S/PbK173-R groups was significantly enhanced （P<0.01）， and the osmotic fragility of the PbK173-S group was significantly stronger than that of the PbK173-R group （P<0.01）. The osmotic fragility of red blood cells in the PbK173-S group during the administration period was significantly stronger than that in the control group and PbK173-R group during the administration period （P<0.01）. The osmotic fragility of red blood cells in the PbK173-R group during the recovery period was significantly higher than that in the control group during the administration period and the PbK173-S group during the recovery period （P<0.05）. Compared with those in the control group， the Piezo1 protein and Band3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced （P<0.01）. Compared with those in the PbK173-R group， the Piezo1 protein and Band 3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced. ConclusionThe flexibility of PbK173-infected red blood cells with different sensitivities to artemisinins differed. Plasmodium-infected red blood cells significantly reduced the levels of Piezo1 and Band3 proteins in the red blood cell membrane， and the erythrocyte flexibility exhibited a decreasing trend in the following order： normal group， PbK173-R group， and PbK173-S group.

The ethics committee of organ transplantation technology and clinical application in a hospital has encountered some difficulties and typical cases in its review work and practice for many years. Sometimes, it is difficult to make a decision in these dilemmas. Based on the previous experience of the hospital in the ethical review of organ donation and transplantation, combined with two typical cases, this paper discussed and analyzed two review points of whether the voluntary unpaid donation and the principle of informed consent were met, and whether the risk-benefit ratio was reasonable, and put forward relevant ethical and legal countermeasure for further research by institutional ethics committees and other parties, in order to provide reference for discussing the practical problems and ethical confusion of ethical review of organ donation and transplantation.

Bariatric surgery may cause intestinal microecological environment imbalance due to changes in gastrointestinal anatomy.Some patients may have compli-cations,even regain weight.Probiotics can act on intestinal mucosa,epithelium and gut-associated lymphoid tissue to improve the intestinal microecological environment of obese patients after bariatric surgery.Probiotics can promote the production of short-chain fatty acids,stimulate intestinal cells to release glucagon-like peptide-1,peptide tyrosine-tyrosine,insulin and other endocrine hormones,affect the function of the central nervous system through the gut-brain axis,make patients after bariatric surgery feel full,and reduce blood sugar at the same time.Probiotics can produce lactic acid,acetic acid and lactase,to inhibit the growth of harmful bacteria and to improve gastrointestinal symptoms of patients after bariatric surgery.Probiotics can activate the AMP-activated protein kinase signaling pathway,improve lipid metabolism,and promote the recovery of symptom indicators of nonalcoholic fatty liver disease after bariatric surgery.Probiotics can regulate the release of neurotransmitters or metabolites by the microbiota through the gut-brain axis to affect brain activity and behavior,thus helping patients improve negative emotions after bariatric surgery.This article describes the intestinal microecological environment of obese patients and mechanism of the change after bariatric surgery and summarizes the effects and possible mechanisms of probiotics in improving the intestinal microecological environment of obese patients after bariatric surgery,to provide references for promoting the clinical application of probiotics.

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.