Dry eye disease(DED)is a common ocular surface disorder worldwide, primarily characterized by a loss of homeostasis of the tear film, and frequently associated with meibomian gland dysfunction(MGD), decreased tear film stability, ocular discomfort, and visual impairment. In recent years, factors such as the widespread use of digital devices,the aging population, and environmental changes have contributed to a significant increase in its global prevalence, making it a major public health concern. Red light therapy(RLT), also known as low-level laser therapy(LLLT)or photobiomodulation(PBM), is a non-invasive treatment that utilizes low-energy red or near-infrared light to irradiate tissues. It exerts photobiomodulatory effects to promote cellular repair and functional recovery. This therapy has demonstrated considerable potential in treating various ocular conditions. Its broader clinical application could improve therapeutic outcomes, alleviate patient discomfort and financial burden, and reduce the consumption of healthcare resources, thereby yielding significant socio-economic benefits. This paper systematically reviews the multifaceted mechanisms and application prospects of RLT in managing DED, including its anti-inflammatory effects, improvement of meibomian gland function, promotion of conjunctival goblet cell repair, and alleviation of visual fatigue, aiming to provide a theoretical foundation and practical reference for its clinical adoption.

ObjectiveThis study focused on the marketed Chinese patent medicines for the treatment of Functional Diarrhea （FDr） in China and their prescription characteristics， in order to provide support for the clinical application and research and development of anti-FDr Chinese patent medicines. MethodsCollect the information of Chinese patent medicines that have been marketed to treat FDr， use Microsoft Excel 2021 software to conduct preliminary data collation and statistical analysis， and use the ancient and modern medical record cloud platform （V2.3.9） to analyze the standardized Chinese patent medicine prescriptions from the aspects of drug nature and taste， medication characteristics and prescription rules. Results147 kinds of FDr Chinese patent medicines were included in this study. There are a total of 40 varieties of FDr Chinese patent medicines suitable for children； The distribution of dosage forms is mainly pills， tablets， and capsules. 110 prescriptions were screened， among which the proportion of Chinese patent medicines for the treatment of spleen deficiency syndrome was the highest； The top three drug use frequency were licorice， Atractylodes macrocephala， and Poria cocos； The medicinal properties are mainly warm and flat， and the medicinal taste is mostly pungent， sweet and bitter， and most of them belong to the two meridians of the spleen and stomach； The association rules analysis obtains 20 strong association pairing sets； Three drug combinations were obtained by cluster analysis. ConclusionFDr Chinese patent medicine shows unique value in clinical application， especially in the field of children. However， there are still problems such as strong professionalism in the indication expression of drug instructions， limited coverage of the medical insurance catalog， and lack of high-level evidence-based medicine and pharmacoeconomic evidence. To this end， in the future， efforts should be made to build a multi-level evidence-based evidence system， improve medication compliance， and deepen research on syndrome-based medication laws， so as to enhance the clinical application value and scientific connotation of FDr Chinese patent medicines.

Sufficient bone tissue is required to ensure the long-term stability of implants. Based on the principles of guided bone regeneration, Dr. Istvan Urban proposed the “sausage technique”. Research indicates that the horizontal bone augmentation observed with the sausage technique averages (5.3 ± 2.3) mm and the vertical bone augmentation averages (4.2 ± 1.9) mm, which is significantly greater than the outcomes achieved with traditional guided bone regeneration techniques. The sausage technique is reliable because the biological membrane has sufficient elasticity and toughness with the application of membrane screws, which stabilizes the mixture of autologous bone and bone graft materials in the bone grafting area and prevents the grafting materials from being displaced. Using substitute materials for autologous bone graft balances the osteogenic activity and the low graft absorption rate. A ball drill is used to prepare nourishing holes in the cortical bone of the recipient area, providing a pathway for mesenchymal stem cells and bone progenitor cells to migrate to the bone regeneration area. Furthermore, this method accelerates the early angiogenesis of wound healing, fully reduces tension during suturing, and ensures that excessive pressure is not applied to the healing area during suturing. Thus, the sausage technique is consistent and reliable. Despite the good outcomes demonstrated by the sausage technique in clinical applications, its potential complications related to soft and hard tissue have attracted widespread attention. These complications negatively affect the patient’s recovery process and influence the final results of the surgery. Therefore, a complete understanding of the complications associated with the sausage technique and their underlying causes is necessary to enhance the clinical safety and effectiveness of the sausage technique. This article summarizes the application principles, clinical effects, barrier membrane applications, selection of bone transplant materials, and related complications of the sausage technique, aiming to provide a reference for clinical application.

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Objective: To investigate the status quo and associated factors of drinking water knowledge, attitude and behavior among primary school students in rural areas, so as to provide evidence for health behavioral intervention of drinking water in primary school. Methods: Twentythree primary schools in rural area from Hebei, Henan, Shandong and Shanxi provinces were selected by using purposive sampling method from March 1 to April 27 in 2023. Selfdesigned questionnaires regarding knowledge, attitude and behavior of drinking water were distributed to all students in grade 3-6, and 2 173 valid questionnaires were obtained. Multivariate Logistic regression was used to analyze the influencing factors of drinking water knowledge, attitude and behavior of primary school students. Results: The attainment rates of drinking water knowledge, attitude and behavior level were 20.02%, 26.65%, and 31.20%, respectively, among primary school students. The median of daily water intake was 1 000 mL, and the average daily water intake was (1 172.99±771.89)mL. In addition, 66.31% of students water intake reached the minimum standard of 800 mL recommended. The results of multiple Logistic regression indicated that drinking water accessibility in school, health education of drinking water, and individual selfcontrol ability were positively correlated with the knowledge (OR=1.31, 1.57, 1.58), attitude (OR=2.07, 1.65, 1.73), behavior (OR=1.40, 1.49, 1.91) of drinking water and daily water intake (OR=1.41, 1.38, 1.20) (P<0.05). Conclusions Primary school students in rural areas are generally lack of appropriate health awareness on drinking water including knowledge, attitude and behavior. Schools should take targeted measures to focus on the cultivation of students selfcontrol ability, so as to improve students knowledge and attitudes of drinking water, and furthermore help students shape their healthy behaviors of drinking water.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

OBJECTIVE To introduce the characteristics and practice of billable pharmacy service programs in the United States， aiming to provide reference for the development of clinical pharmacy service and the establishment of corresponding billing criteria in China. METHODS By searching the official websites of American Pharmacists Association， American Society of Health- System Pharmacists， Centers for Medicare & Medicaid Services and Centers for Disease Control and Prevention， and the PubMed database， the contents of American billable pharmacy service programs， corresponding service billing criteria， the approaches to being paid as pharmacists and the clinical practice evidence were summarized. RESULTS Current major billable pharmacy service programs implemented in the United States included medication therapy management， outpatient pharmacy service， transition of care management， chronic disease management， annual wellness visits， as well as diabetes self-management training/education. Except for diabetes self-management training/education， which lacked robust data on practice outcomes， all other programs mentioned above were demonstrated to have positive impact on patient outcomes， reducing health care cost and/or generating revenues. The most common approaches for pharmacists to obtain reimbursement were “incident to” billing and using procedure codes. CONCLUSIONS Billable pharmacy practice programs in the United States are achieving progress in service specialization and billing standardization. China can learn from successful cases in the United States while considering its own national context， with the ultimate goal of improving the overall health outcomes of patients， so that pharmacy services can become an important part of the medical service system.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.