In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.

OBJECTIVE To provide references for ensuring the safety of prescription preparation， dispensing， and use of parenteral nutrition solution， as well as for expanding the scope of pharmaceutical services provided by pharmacists in the Pharmacy Intravenous Admixture Services （PIVAS）. METHODS Under the guidance of PIVAS pharmacists， the rules for reviewing medical orders of parenteral nutrition in the PIVAS system and the information displayed on the infusion labels of finished parenteral nutrition solutions were refined. The process management of dispensing parenteral nutrition solution was strengthened， and detailed quality control and inspection rules were formulated. Additionally， Clinical Safety Monitoring Form for Finished Parenteral Nutrition Infusions was designed to conduct clinical monitoring and inspections for abnormalities in the finished infusions， infusion operations， and complications that may arise during the use of finished parenteral nutrition infusions. The implementation effects of the aforementioned optimization/inspection measures were evaluated by comparing data on the efficiency of medical order review for parenteral nutrition， the rate of irrational medical orders， the compliance rate of vascular access selection and infusion rate standardization， the rate of dispensing error， as well as the abnormalities occurring during clinical use， before and after the optimization/inspection initiatives were put into place. RESULTS The optimized prescription review system achieved automatic review of medical orders for parenteral nutrition， enhancing the efficiency of order review. The average time taken to review one parenteral nutrition medical order was reduced from approximately 1 minute to 10 seconds. The irrational rate of parenteral nutrition orders decreased by 31.87%. The dispensing error rate of parenteral nutrition decreased by 56.55%. The standard rate of vascular access selection and standard rate of infusion speed were increased by 13.29% and 3.54%， respectively. The PIVAS pharmacists identified and intervened in 5 abnormal cases out of 298 cases examined for use of parenteral nutrition solutions. CONCLUSIONS By optimizing the prescription review system， improving labeling information， and strengthening quality control inspections during both preparation and administration processes， PIVAS pharmacists have enhanced the safety of compounded parenteral nutrition solutions. This initiative has expanded the scope and depth of pharmaceutical care provided by dispensing pharmacists.

This study aimed to investigate the effects of Zhiwei Fuwei Pills on mitochondrial apoptosis in the rat model of precancerous lesions of gastric cancer(PLGC) based on the microRNA-21(miRNA-21)/B-cell lymphoma-2(Bcl-2) signaling pathway. Eighty-five 5-week-old male SPF-grade SD rats were selected, of which 75 were fed with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) for multifactorial modeling, and the PLGC model was established after 26 weeks. The rats were randomly grouped as follows: model, folic acid(0.002 g·kg~(-1)), low-dose(0.42 g·kg~(-1)) Zhiwei Fuwei Pills, medium-dose(0.84 g·kg~(-1)) Zhiwei Fuwei Pills, and high-dose(1.67 g·kg~(-1)) Zhiwei Fuwei Pills, with 15 rats in each group. Additionally, 10 rats were assigned to a blank group and administrated with an equivalent volume of normal saline by gavage. After four weeks of continuous drug administration, the gastric mucosal tissue was collected. Hematoxylin-eosin(HE) staining was performed to reveal the pathological changes in the gastric mucosa. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) was employed to detect apoptosis in gastric mucosal epithelial cells. RT-PCR was adopted to determine the mRNA levels of miRNA-21, phosphatase and tensin homolog(PTEN), Bcl-2, Bcl-2-associated X protein(Bax), and cysteinyl aspartate-specific protease 3(caspase-3). Western blot was employed to determine the protein levels of PTEN, Bcl-2, Bax, and caspase-3. Immunohistochemistry(IHC) was used to detect the positive expression of PTEN, Bcl-2, and Bax in the gastric mucosal tissue. Transmission electron microscopy(TEM) was employed to observe the morphological and structural changes in mitochondria. The results showed that compared with model group, the drug administration groups showed alleviated pathological changes, with increased apoptotic cells, down-regulated mRNA levels of miRNA-21 and Bcl-2, up-regulated mRNA and protein levels of PTEN, Bax, and caspase-3, and down-regulated protein level of Bcl-2. In addition, the drug administration groups exhibited mitochondrial swelling and rupture and reduction of cristae, which indicated mitochondrial apoptosis. These findings suggest that Zhiwei Fuwei Pills can effectively improve mitochondrial apoptosis in PLGC cells by regulating the miRNA-21/Bcl-2 signaling pathway.
Animals ; MicroRNAs/metabolism* ; Male ; Apoptosis/drug effects* ; Stomach Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Rats ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Mitochondria/genetics* ; Signal Transduction/drug effects* ; Precancerous Conditions/drug therapy* ; Humans ; PTEN Phosphohydrolase/genetics*

OBJECTIVE: To explore short-term clinical efficacy of minimally invasive diagnosis and treatment system for hallux valgus in guiding the treatment of hallux valgus. METHODS: From March 2021 to November 2023, 68 patients (136 feet) with hallux valgus were treated under guidance of minimally invasive diagnosis and treatment system, including 12 males and 56 females;aged from 25 to 68 years old with an average of (42.5±8.5) years old, the course of disease ranged from 3.2 to 15.6 years with an average of (10.3±2.6) years. The changes of hallux valgus angle (HVA) and intermetatarsal angle (IMA), visual analog scale (VAS) and American Orthopaedic Foot Ankle Society (AOFAS) forefoot score were recorded and compared before operation and 12 months after operation. RESULTS: Sixty-five patients (130 feet) were followed up for 12 to 15 months with an average of (13.8±0.5) months, 3 patients (6 feet) were not followed up as required. HVA and IMA improved from (35.5±3.5) ° and (12.5±2.0) ° before operation to (10.5±2.5) ° and (8.5±1.5) °12 months after operation, respectively, with statistically significant differences (P<0.05);VAS decreased from (5.5±1.2) before operation to (1.2±0.5) at 12 months after operation, and the difference was statistically significant (P<0.05);AOFAS forefoot score increased from (50.6±5.1) before operation to (93.8±5.6) at 12 months after operation, with a statistically significant difference (P<0.05). Among them, 102 feet were got excellent result, 24 feet good, and 4 feet fair. Two patients were developed calf intermuscular vein thrombosis, and were cured after 3 months of symptomatic treatment. CONCLUSION Under the guidance of minimally invasive diagnosis and treatment system for hallux valgus, the treatment of HV could obviously improve HVA and IMA, and significantly alleviate pain symptoms, and accelerate functional recovery.
Humans ; Hallux Valgus/diagnosis* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Minimally Invasive Surgical Procedures/methods* ; Treatment Outcome

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

OBJECTIVE: To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax, chidamide, and azacitidine in the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 15 elderly AML patients aged≥60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax, chidamide and azacitidine, and the efficacy, treatment-related adverse events, overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: After one course of treatment, 11 out of 15 patients achieved complete response (CR), 3 patients achieved CR with incomplete hematologic recovery (CRi), and 1 patient died due to prior infection before efficacy evaluation, and the overall response rate (ORR) was 93.3% (14/15). The median follow-up time was 131 (19-275) days, with median OS and EFS both remaining unreached. Next-generation sequencing (NGS) analysis showed that among the 15 patients, 13 were detected with gene mutations, and there were 7 genes with mutation frequencies of more than 10%, including ASXL1 (4 cases), RUNX1 (4 cases), BCOR (3 cases), DNMT3A (3 cases), STAG2 (2 cases), IDH1/2 (2 cases), and TET (2 cases). Among the 13 patients with detectable mutations, 12 patients achieved composite response (CR+CRi). The average recovery time of white blood cell count was 14.6 days after chemotherapy, and the average recovery time of platelets was 7.7 days after chemotherapy. The main adverse event was myelosuppression, with 10 patients accompanied by infection. Except for 1 patient who died due to septic shock during chemotherapy, no patients experienced serious complications such as heart, liver, or kidney damage during the treatment process. CONCLUSION The CACAG+V regimen, which combines the CAG regimen with venetoclax, chidamide, and azacitidine, can be applied in the treatment of elderly AML patients, demonstrating good safety and induction remission rate.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Azacitidine/therapeutic use* ; Aged ; Benzamides/therapeutic use* ; Male ; Female ; Treatment Outcome ; Middle Aged ; Cytarabine ; Aclarubicin ; Granulocyte Colony-Stimulating Factor

BackgroundBariatric surgery has emerged as an important tool in the management of obesity. Some patients undergoing bariatric surgery are prone to develop emotional abnormalities and have abnormally elevated concentrations of inflammatory factors level in peripheral blood， whereas current domestic research focusing on the impact of preoperative emotional states and peripheral blood inflammatory factors level on weight loss effect remains limited. ObjectiveTo explore the correlation of preoperative emotional abnormalities with the effectiveness of bariatric surgery in obese patients， and to provide theoretical basis for improving the clinical efficacy of bariatric surgery. MethodsEighty-one obese patients scheduled for bariatric surgery at gastrointestinal surgery Department of West China Hospital， Sichuan University from December 30， 2022 to June 30， 2023 were enrolled and assessed using Hamilton Depression Scale-17 item （HAMD-17） and Hamilton Anxiety Scale （HAMA）. Patients who scored 7 or above on HAMD-17 or HAMA or had a history of previous depression or anxiety diagnoses were classified into emotional abnormality group （n=34）， and samples who scored less than 7 on HAMD-17 and HAMA and were free of history of previous depression and anxiety diagnoses were set as non-emotional abnormality group （n=47）. The data were collected by the self made questionnaire. Patients were subjected to complete the assessment of Beck Scale for Suicide Ideation-Chinese Version （BSI-CV）， Eating Disorder Inventory （EDI） and Pittsburgh Sleep Quality Index （PSQI）. Laboratory tests including peripheral blood C-reactive protein （CRP） and interleukin-6 （IL-6）. Body weight and height assessed in the early morning after an overnight fasting period were recorded in all participants at 1- and 6-month after surgery through outpatient clinic visits or telephone follow-up. Pearson correlation coefficient was used to examine relationship among body mass index （BMI）， preoperative emotional states and peripheral blood inflammation mediators. ResultsAmong 81 obese patients， 62 completed the study， including 27 cases in emotional abnormality group and 35 cases in non-emotional abnormality group. Emotional abnormality group scored higher on BSI-CV （current）， BSI-CV （worst）， EDI and PSQI， and detected higher levels of CRP and IL-6 compared with non-emotional abnormality group （Z=2.677， 2.975， t=3.573， 4.035， 1.990， 2.799， P<0.05 or 0.01）. For BMI， there was no significant group effect and time×group interaction effect （P>0.05）， but a significant time effect （F=227.740， P<0.01）. Within emotional abnormality group， BMI at the baseline， 1- and 6-month after surgery showed a positive correlation with IL-6 level （r=0.419， 0.510， 0.559， P<0.05 or 0.01）， BMI at 6-month after surgery was positively correlated with HAMD-17 total score （r=0.390， P<0.05）， and ΔBMI% at 6-month after surgery was negatively correlated with HAMD-17 total score （r=-0.421， P<0.05）. Within non-emotional abnormality group， baseline BMI was positively correlated with IL-6 level （r=0.338， P<0.01）. ConclusionThe short-term effect of bariatric surgery may be comparable in obese patients with or without emotional abnormalities， while it cannot be ruled out whether the outcome of bariatric surgery is related to the severity of preoperative depression.

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

Laminar organization is a hallmark of the mammalian neocortex, where the orderly arrangement of diverse neurons stereotypically forms into six distinct layers. The laminar structure provides a basis for the formation of precise neural circuits responsible for high-level cognitive functions. A deeper understanding of the mechanisms underlying neocortical layer formation and cell assembly in the brain will provide a more comprehensive insight into mammalian and even human physiology and behavior. It will also enable the development of novel diagnostic and therapeutic strategies for neurological disorders. To achieve this, it is imperative to elucidate the molecular regulatory networks that determine the fate of neurons in the neocortex. MicroRNAs (miRNAs) are small non-coding RNAs of 18-25 nucleotides in length that play important roles in the gene expression network. A large number of studies have reported that miRNAs are involved in various developmental processes within the nervous system. This review summarizes the progress of research on miRNAs that have been identified in recent years with regard to neocortical layer formation. We start with a comparative analysis of different Cre-line mediated conditional knockout mice for Dicer, a gene indispensable for the synthesis of almost all miRNAs. The results indicate that miRNAs are essential for the formation of neocortical layers, including the determination of the fate of projection neurons and the migration of these cells. Next, we summarize the regulatory roles of miRNAs in the coordinated execution of a series of developmental events that contribute to neocortical layer formation. First, the temporal patterning of neocortical neural progenitors is regulated by miRNAs. Two types of temporally opposite expression gradients and functionally antagonistic miRNAs modulate the competence of neural progenitors by changing their relative expression levels during neurogenesis, thereby shifting the progressive generation of neocortical neurons. Second, it is described that miRNAs influence lamination by regulating the fate of intermediate progenitor cells (IPCs). In particular, several miRNAs that are specifically expressed in multiple gyrencephalic species have been identified in recent years and are involved in regulating the generation of IPCs as well as the generation of upper layer neurons. Third, the regulatory roles of miRNAs in the migration of cortical projection neurons, including the multipolar to bipolar transition and other processes, were presented. Fourth, we described miRNAs that are expressed in postmitotic neurons but play roles in the further specification of different cortical projection neuron subtype identities, in particular the role of several miRNAs in the Mirg cluster in establishing different subtype identities of projection neurons in layer V, promoting corticospinal motor neuron (CSMN) identity but inhibiting callosal projection neuron (CPN) identity. Finally, we discussed current challenges in the study of miRNAs in neocortical layer formation and looked forward to future directions that deserve further exploration, such as the functions of a large number of newly discovered miRNAs, or whether miRNAs regulate the layer-dependent pattern of other neuronal cells with layer distribution features; the contribution of miRNAs in the rapid evolution of the neocortex, especially in the formation of characteristic structures in the primate neocortex; and the use of miRNAs as an entry point to explore finer regulatory networks.

BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P＜0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.