Huaihuasan， first recorded in Experiential Prescriptions for Universal Relief （Pu Ji Ben Shi Fang）， is a classic prescription for the treatment of ''hematochezia due to intestinal wind''. In 2018， it was included by the National Administration of Traditional Chinese Medicine as one of the first 100 classic prescriptions. This formula consists of four ingredients， i.e.， Sophorae Flos， Platycladi Cacumen， Schizonepetae Spica， and Aurantii Fructus. It is known for its ability to clear the intestines， dispel wind， cool the blood， and stop bleeding. In modern clinical practice， Huaihuasan， often with modifications， is widely used to treat various digestive tract diseases， including ulcerative colitis （UC）， with significant long-term effects. UC is a chronic， non-specific inflammatory bowel disease. Currently， Western medicine primarily treats UC with glucocorticoids， aminosalicylates， and immunosuppressants， which have good short-term efficacy but numerous adverse reactions， high recurrence rates， and the need for lifelong medication. Modern clinical studies have shown that Huaihuasan can significantly improve symptoms of UC， such as abdominal pain and diarrhea， reduce disease activity scores （Sutherland）， promote intestinal mucosal healing， alleviate anxiety and depression， and significantly improve the quality of life of patients. Pharmacological studies have shown that the main active components of Huaihuasan include quercetin， rutin， kaempferol， naringenin， and volatile oils. These compounds exert their effects by inhibiting inflammatory responses and protecting the intestinal mucosal barrier. They also exhibit antioxidant properties and regulate various signaling pathways， including tumor necrosis factor-α （TNF-α）， interleukin-2 （IL-2）， interleukin-4 （IL-4）， interleukin-1β （IL-1β）， monocyte chemoattractant protein-1 （MCP-1）， nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， and the KRAS-regulated mitogen-activated protein kinase （MEK）-extracellular signal-regulated kinase （ERK） pathway. These multi-target pathways improve UC symptoms， inhibit inflammation-cancer transition， and help maintain intestinal homeostasis. However， the precise mechanism of action has not yet been systematically elucidated. This paper reviews the research progress on Huaihuasan and main ingredients from its component drugs， focusing on their effects against UC. It also discusses current research limitations and suggests strategies for improvement， aiming to provide a reference for further studies on Huaihuasan in the treatment of UC and the development of new drugs.

Objective: To determine the heterogeneity for caries prevention service preferences among children in Anhui Province, so as to provide reference for the promotion and popularization of caries prevention services for school age children. Methods: Based on a discrete selection experiment, a face to face questionnaire survey was administered using a multi stage sampling method among 785 parents with children 3-12 years of age who were hospitalized in the stomatology clinics of 7 prefectures and cities in Anhui Province from October 2021 to October 2022. A mixed Logit model was used to evaluate caries prevention service preferences for children. Results: Four discrete choice experiment attributes included in the study were statistically significant for choice preference ( P <0.05). Compared with the control group, parents with a high school education or above preferred caries prevention services with 70%-<80% preventive effectiveness, 2-<5 and <2 km from the service point, and a high service cost ( β =0.38, 1.66, 1.64, 0.00); female parents preferred preventive services with 70%-<80% preventive effectiveness and a high service cost ( β =0.35, 0.01 ); parents of children <7 years of age preferred services with 70%-<80% preventive effectiveness ( β =0.75); parents of children with oral health preferred preventive services during winter and summer vacations ( β =-0.28); parents of children with caries preferred preventive services with a high cost per denticle ( β =0.00)( P <0.05). Conclusions Parents with different education levels, gender, child age, and oral health status have heterogeneity in dental caries prevention service preferences. The provision of targeted and precise services can improve the participation and coverage of caries prevention services for school age children.

Objective To investigate the bacterial community diversity in human Demodex mites, so as to provide insights into unraveling the role of human Demodex mites in them caused infectious diseases. Methods From June to July 2023, Demodex mites were collected from the faces of college students in a university in Wuhu City using the adhesive tape method, and the V4 region of 16S ribosomal RNA (16S rRNA) gene and the internal transcribed spacer (ITS) gene of nuclear ribosomal DNA were amplified on an Illumina PE250 high-throughput sequencing platform. Sequencing data were spliced according to the overlapping relations and filtered to yield effective sequences, and operational taxonomic units (OTUs) was clustered. The diversity index of obtained OUTs was analyzed, and the structure of the bacterial community was analyzed at various taxonomic levels. Results A total of 57 483 valid sequences were obtained using 16S rRNA gene sequencing, and 159 OUTs were classified according to similarity. Then, OUTs at a 97% similarity were included for taxonomic analyses, and the bacteria in Demodex mites belonged to 14 phyla, 20 classes, 51 orders, 72 families, and 94 genera. Proteobacteria was the dominant phylum, and Vibrio, Bradyrhizobium and Variovorax were dominant genera. A total of 56 362 valid sequences were obtained using ITS gene sequencing, and 147 OTUs were obtained, which belonged to 5 phyla, 17 classes, 34 orders, 68 families, and 93 genera and were annotated to Ascomycota, Basidiomycota and Chytridiomycota, with Ascomycota as the dominant phylum, and Alternaria alternata, Epicoccum, Penicillium, and Sarocladium as dominant genera. Conclusions There is a high diversity in the composition of bacterial communities in human Demodex mites, with multiple types of microorganisms and high species abundance.

A GC-LSTM model is proposed based on the characteristics of global optimization of genetic algorithm.The model automatically and iteratively searches the optimal hyper-parameter configuration of the C-LSTM model through the genetic algorithm of a specific genetic strategy,and it is configured using the genetic iteration results and validated on the MIT-BIH arrhythmia database according to the classification criteria of the Association for the Advancement of Medical Instrumentation.The testing shows that the classification accuracy,sensitivity,accuracy and F1 value of GC-LSTM model are 99.37%,95.62%,95.17%and 95.39%,respectively,higher than those of the manually established model,and it is also advantageous over the existing mainstream methods.Experimental results demonstrate that the proposed method can achieve better classification performance while avoiding a large number of experimental parameters.

Objective To elucidate the role of programmed cell death factor 4(PDCD4)in mitochondrial dysfunction caused by sepsis-related vascular endothelial damage.Methods Cultured human umbilical vein endothelial cells(HUVECs)and mouse vascular endothelial cells(C166 cells)were transfected with a small interfering RNA targeting PDCD4 followed by treatment with lipopolysaccharide(LPS)alone or in combination with carbonyl cyanide 3-chlorophenylhydrazone(FCCP).The proteomic changes in the cells after PDCD4 knockdown were analyzed using LC-MS/MS technique.The mRNA expressions of PDCD4 and the genes associated with cell inflammation and apoptosis were detected with RT-PCR,and the expressions of FIS1,DRP1 and OPA1 proteins key to mitochondrial fission and fusion were determined using Western blotting.JC-1 and MitoSOX fluorescent probes were used to observe the changes in mitochondrial membrane potential and mitochondrial reactive oxygen species levels under by a laser confocal microscope.Results LPS stimulation of the cells significantly increased the mRNA expressions of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP1)and enhanced the cellular expression of PDCD4(P<0.05).Proteomic analysis suggested a correlation between PDCD4 knockdown and changes in mitochondrial dynamics in the cells.LPS treatment significantly increased the expressions of mitochondrial fission proteins FIS1 and DRP1 and lowered the expression of the fusion protein OPA1 in the cells(P<0.05),causing also mitochondrial oxidative stress and reduction of the mitochondrial membrane potential(P<0.05).In HUVECs,treatment with FCCP significantly attenuated the protective effect of PDCD4 knockdown,which inhibited LPS-induced inflammation and oxidative stress and restored the balance between mitochondrial fission and fusion.Conclusion PDCD4 knockdown protects vascular endothelial cells against LPS-induced damages by repressing mitochondrial fission and oxidative stress,promoting mitochondrial fusion,and maintaining normal mitochondrial function.

Objective To elucidate the role of programmed cell death factor 4(PDCD4)in mitochondrial dysfunction caused by sepsis-related vascular endothelial damage.Methods Cultured human umbilical vein endothelial cells(HUVECs)and mouse vascular endothelial cells(C166 cells)were transfected with a small interfering RNA targeting PDCD4 followed by treatment with lipopolysaccharide(LPS)alone or in combination with carbonyl cyanide 3-chlorophenylhydrazone(FCCP).The proteomic changes in the cells after PDCD4 knockdown were analyzed using LC-MS/MS technique.The mRNA expressions of PDCD4 and the genes associated with cell inflammation and apoptosis were detected with RT-PCR,and the expressions of FIS1,DRP1 and OPA1 proteins key to mitochondrial fission and fusion were determined using Western blotting.JC-1 and MitoSOX fluorescent probes were used to observe the changes in mitochondrial membrane potential and mitochondrial reactive oxygen species levels under by a laser confocal microscope.Results LPS stimulation of the cells significantly increased the mRNA expressions of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP1)and enhanced the cellular expression of PDCD4(P<0.05).Proteomic analysis suggested a correlation between PDCD4 knockdown and changes in mitochondrial dynamics in the cells.LPS treatment significantly increased the expressions of mitochondrial fission proteins FIS1 and DRP1 and lowered the expression of the fusion protein OPA1 in the cells(P<0.05),causing also mitochondrial oxidative stress and reduction of the mitochondrial membrane potential(P<0.05).In HUVECs,treatment with FCCP significantly attenuated the protective effect of PDCD4 knockdown,which inhibited LPS-induced inflammation and oxidative stress and restored the balance between mitochondrial fission and fusion.Conclusion PDCD4 knockdown protects vascular endothelial cells against LPS-induced damages by repressing mitochondrial fission and oxidative stress,promoting mitochondrial fusion,and maintaining normal mitochondrial function.

Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.

Ghrelin is a hormone produced by the stomach that regulates energy metabolism after acting on the central nervous system.Cocaine amphetamine-regulated transcriptional peptide(CART)neurons participate in the regulation of feeding behavior and energy balance.It is known that CART neurons are influenced by hormones to regulate energy homeostasis,but whether ghre-lin exerts its pro-appetite function by influencing CART neurons is unknown.Therefore,this study focuses on the role of VMHCART neurons in the regulation of feeding and relative body weight by ghrelin.Firstly,the whole brain expression of CART was determined by immunofluorescence.Then the effect of intraperitoneal injection of ghrelin on the expression of DMHCART neurons was evalua-ted.Finally,the ghrelin was delivered to DMH and the changes of food intake and relative body weight of mice were measured.CART immunoreactive neurons were detected in medial preoptic nucleus(MPA),arcuate nucleus(ARC),dorsomedial hypothalamic nucleus(DMH),thalamic pa-raventricular nucleus(PVT)and raphe nucleus(ROb).Compared with the control group,periph-eral injection of ghrelin significantly increased the expression of DMHC ART immunoreactive neurons(P=0.037 3).DMH long-term injection of ghrelin resulted in an increase in body weight(P=0.004 0)and feed intake(P=0.023 1).The results provide anatomical evidence for the whole brain distribution of CART,which proves that ghrelin affects feed intake and body weight of mice through CART neurons in DMH,suggesting that specific neuron types and regional specificity are involved in ghrelin regulation of feed intake and energy homeostasis.

Vesicular glutamate transporter 2(VGlut2)is expressed in the PVN of the hypothalamic paraventricular nucleus(PVNVG1ut2)as an excitatory neurotransmitter,which regulates food intake and energy metabolism and plays an important role in maintaining homeostasis.However,it is not clear that the upstream and downstream projection network of PVNVGut2 neurons hinders the anal-ysis of glutamatergic neuron circuit function.Anterograde and retrograde tracer viruses were injec-ted into the PVN of VGlut2 mice by stereotactic brain injection technique to find the input and output nuclei of PVNVGlut2 neurons.Anterograde tracing results showed that PVNVGlut2 neurons pro-jected to the downstream medial amygdala(MeAD)and arcuate nucleus(ARC).Retrograde trac-ing results showed that PVNVGlut2 received input from the prefrontal nucleus(Pr),the reticular tegmental nucleus(RtTg),and the hypoglossal nucleus(12N).In addition,VGlut2 was found to be co-expressed with neuronal nitric oxide synthase(nNOS)neurons in the PVN.The anatomical net-work of PVNVG1ut2 neurons was analyzed by virus tracking tool,which laid the anatomical founda-tion for further study on the functional regulation of PVNVGlut2.

Pancreatic cancer is a malignant tumor of digestive system with poor prognosis. It has the characteristics of low early diagnosis rate, low feasible operation rate and low treatment success rate. Most patients are in advanced stage when they are found. Chemotherapy and immunotherapy are important treatments for pancreatic cancer because of its low operative rate. However, the extracellular matrix (ECM) of pancreatic cancer forms a special physical and metabolic barrier, which reduces the effect of chemotherapy and immunotherapy. Cancer associated fibroblast (CAF) are tumor promoting cells in the extracellular matrix and are novel targets for anti-tumor interventions. However, the lack of specific markers and unknown differences between CAF subtypes have hindered relevant clinical trials. This article reviews the origin and functional diversity of CAF, and discusses the clinical progress and treatment strategies of CAF and pancreatic cancer.