OBJECTIVE To explore the effects of prescription pre-review system on rational drug use and off-label drug use management in outpatient and emergency department. METHODS A retrospective analysis was conducted on outpatient and emergency department prescription data from three phases in our hospital： January to May 2023 （silent review phase， control group）， June to October 2023 （systematic automatic review phase， intervention group 1）， and November 2023 to March 2024 （phase combining systematic automatic review with centralized feedback from pharmacists to physicians regarding irrational prescriptions， intervention group 2）. These phases followed the implementation of our hospital’s pre-prescription review software. Statistical analysis of the prompt rate of alert， rate of irrational prescriptions， registered the off-label drug use rate and false positive irrationality prescription rate were conducted. Meanwhile， the composition of irrational prescriptions was analyzed， and evidence- based evaluation of the off-label drug use proposed by clinicians was also conducted. RESULTS Compared with control group， the prompt rate of alert and the rate of irrational prescriptions in intervention group 1 were all decreased significantly after receiving pop-up notification， with statistically significant differences （P＜0.05）. With the help of system warning and the pharmacists feedback， the prompt rate of alert and the rate of irrational prescriptions declined further in the intervention group 2， but there was no statistically significant difference when compared with intervention group 1 （P＞0.05）. The main type of irrational drug use was improper administration routes. When comparing intervention group 1 with the control group， as well as intervention group 2 with intervention group 1， a significant decrease in the rate of improper administration routes was observed， with statistically significant differences （P＜0.05）. Compared with control group， there was no significant difference in the registered off-label drug use rate of intervention group 1 and intervention group 2 （P＞0.05）. The doctor’s awareness of off-label drug use registration increased due to the real-time alerts from the pre-prescription review software， along with the pharmacists’ regular summarization and feedback. Total 13 items registrations of off-label drug use were proposed by clinicians from June 2023 to March 2024， all of which were supported by evidence of varying levels； among them， 3 items received FDA approval， 4 items were included in the Micromedex database， and the remaining 6 items were supported by evidence from system reviews or randomized controlled trials. CONCLUSIONS Prescription pre-review system can improve the level of rational drug use and assist in the standardized management of off-label drug use.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective: To evaluate the effectiveness of the biologically oriented preparation technique (BOPT) in restoring traumatic tooth defects within the aesthetic zone, serving as a clinical reference. Methods: This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Two cases are detailed, involving traumatic tooth defects under the gingival level, repaired using BOPT in the aesthetic region. Both individuals reported defects resulting from trauma to the upper right anterior teeth occurring over a month prior. Case 1: male, 67 years old. The patient complained of a defect and exposed pulp in the right upper front tooth caused by trauma one month ago. Root canal treatment was performed in the dental pulp department, but there was no discomfort after the surgery. Due to the impact on chewing and aesthetics, restoration is required. Oral examination: 11 residual roots, the deepest part of the lip side fracture, in a V-shape, located 2 mm subgingival, 1-2 mm subgingival near and far, and 2-3 mm supragingival on the palatal side fracture. There is little remaining dental tissue, and filling material can be seen at the root canal opening. The proximal and distal diameters are small, and the tooth root is tilted towards the palatal side. After tapping (-), no obvious looseness is observed. 11 missing gingival papilla near and far; 21 dental crowns tilted towards the middle; thick gingival biotype; dental calculus (+), probing depth (PD): 2-4 mm; Attachment loss (AL): 1-2 mm; Gingival recession (GR): 0-1 mm; bleeding index (BI): 1-2, diagnosis: 11 residual roots; chronic periodontitis. Case 2, male, 34 years old. The patient complained of a defect and exposed pulp in the right upper front tooth caused by trauma one month ago. Root canal treatment was performed in the dental pulp department, but there was no discomfort after the surgery. Due to the impact on chewing and aesthetics, restoration is required. Oral examination: Large area defects were found in sections 12 and 13, with the lip side wall defect reaching about 1 mm subgingival and filling visible at the fracture end. The proximal and distal fracture ends were located about 2-4 mm above the gingiva, and the palatal fracture end was located about 3-4 mm above the gingiva. After tapping (-), no obvious looseness was observed, and the lip side gingiva was slightly red and swollen; thick gingival biotype; dental calculus (++~+++); PD: 3-5 mm; AL: 1-3 mm; GR: 0-2 mm; BI: 2-3; diagnosis: 12 and 13 tooth defects; chronic periodontitis. Treatment plan: following systematic periodontal treatment, the BOPT was implemented using vertical tooth preparation. Temporary restorations were employed to sculpt the soft tissue, and high-translucency zirconia all-ceramic crowns were selected. Utilizing computer aided design/computer aided manufacturing technology, the temporary restorations’ contours were meticulously recreated to achieve optimal pink and white aesthetics. Results : The BOPT enables the restoration of traumatic tooth defects in the aesthetic area as well as soft tissue shaping. In Case 1, the patient’s originally palatally inclined the upper right central incisor achieved gingival shaping and harmonized with the upper left central incisor. In Case 2, the previously swollen and poorly shaped gingival margins of the upper right lateral incisor and upper right canine showed significant improvement.By applying the BOPT, the two cases developed healthy soft tissue cuffs, achieving excellent pink and white aesthetic restoration effects. One-year postoperative follow-up of two patients showed that the gingival margins of the upper right central incisor in Case 1 and the upper right lateral incisor and upper right canine in Case 2 were stabilized, with good maintenance of pink and white aesthetic effects. The review of the literatures showed that compared to horizontal tooth preparation, the BOPT combined with a complete digital workflow can be more minimally invasive, using temporary restorations to rebuild the enamel-osteoskeletal contours of the abutment teeth, reshape the soft tissue contours, increase the thickness of the soft tissue, and stabilize the gingival margins. However, the long-term restorative effects still require clinical follow-up observation. Conclusion The BOPT is an effective restorative solution for traumatic teeth in the aesthetic area, as it can be used appropriately in the aesthetic area to obtain good aesthetic restorative effects.

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 material basis and mechanism of Danshen Baizhu prescription in coronary heart disease, vascular dementia and idiopathic membranous nephropathy based on network pharmacology. Methods TCMSP, PubChem, UniProt, GeneCards, OMIM, and DrugBank databases were used to obtain drug and disease targets, and the TCM-compound-drug target network, compound-common target-disease network, and protein-protein interaction map were drawn by STRING database and Cytoscape software, and gene enrichment analysis was performed by Metascape database. Results A total of 164 active compounds, 509 potential targets, and 141 common targets were screened out. The main active ingredients were Tanshinone II A, Isorhamnetin, Quercetin, Luteolin, Kampferol, β-sitosterol, Stigmasterol, etc. The key targets were albumin, interleukin 6, Tumor necrosis factor , serine/threonine kinase 1, vascular endothelial growth factor A , mainly enriching in the positive regulation of cell migration, cell viability, protein phosphorylation, responsing to growth factors, oxidative stress and other biological processes and lipid and atherosclerosis, MAPK, atherosclerosis and fluid shear force, AGE-RAGE, IL-17, PI3K-Akt and other signaling pathways. Conclusion The mechanism of action of Danshen Baizhu prescription for coronary heart disease, vascular dementia and idiopathic membranous nephropathy may mainly play a role in multiple targets and pathways such as inhibition of inflammation, inhibition of oxidative stress, and vasodilation.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus （HBV） infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases， Affiliated Hospital of Yan’an University， from September 2013 to June 2021 were enrolled as subjects， and the degree of liver injury was compared between patients based on age， sex， presence or absence of the family history of hepatitis B， HBsAg， and alanine aminotransferase （ALT） level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection， 86 patients （31.73%） grade≥A2 liver inflammatory activity， 72 （26.57%） had a liver fibrosis stage of ive， and 112 （41.33%） had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L （χ²=3.938， P=0.047）. There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages， sexes， family history of hepatitis B， HBsAg levels （all P>0.05），there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）， and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups （all P>0.05）. There was no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）. ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection， and there is no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B， there is still a considerable proportion of patients with liver injury， which should be taken seriously by clinicians.

Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Parkinson's disease（PD） is the second most common neurodegenerative disease in the world， which seriously affects the lives of patients. With the acceleration of aging process， the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However， the pathogenesis of PD is still unclear. According to reports， the brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra， which is closely related to neurophysiological processes such as neurogenesis， synaptic plasticity， neuroinflammation， and oxidative stress. It plays an important role in the occurrence and development of PD. At present， the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms， but with the increase of dose， the adverse reactions are significantly enhanced. Traditional Chinese medicine（TCM） has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food， economy， minor adverse reactions and multi-target action. Therefore， this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas， extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad， so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.