OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Objective The aim of this study is to retrospectively analyze the clinical and imaging characteristics,treatment and prognosis of 13 patients with granulomatous prostatitis(GP),and to provide reference for the diagnosis and treatment for GP.Methods The clinical information of 13 GP patients extracted from electronic medical records including demographic characteristic risk factors,clinical symptoms,laboratory findings,imaging findings(ultrasound,CT,MRI,FDG-PET-CT),treatment and outcomes were analyzed retrospectively from January 2018 to August 2023 at our center.Results The average age of 13 patients with GP was(65.69±6.46)years.And the average score of IPSS was(23.40±5.8).Five patients appeared positive results,of which 11 cases received digital rectal examination.The average level of pre-biopsy tPSA was(23.28±44.94)μg/L with fPSA/tPSA ratio of 0.11±0.05 and PSAD of(0.55±1.07)μg/l/mL.The pre-biopsy mean MRI PI-RADS 2.0 was(4.6±0.6)in this group of patients.Extraprostatic invasion was shown on imaging in 4 patients.The average number of biopsy needles was(19.6±3.9),and the pathological results showed tuber-culous granulomas in 2 cases(15.4％)and non-specific granulomatous inflammation in 11 cases(84.6％).Five patients received local treatment of the prostate after pathological confirmation(PVP in 4 cases,TURP in 1 case),2 patients re-ceived anti-tuberculosis therapy,and 3 cases were given antibiotics.Average follow-up was(20.6±11.2)months,and the average tPSA were(6.94±4.96)μg/L at 3-6 months after biopsy and/or surgery,with no obvious signs of malignancy during the follow-up period.Conclusion GP is the great mimicker of prostate cancer clinically and radiologically.Pros-tate biopsy is the method for confirming the diagnosis.For patients who are considering biopsy-free radical prostatectomy,it is important to consider the possibility of GP.

Objective:To explore the clinical efficacy of "four-step" aortic valve anatomic repair for bicuspid aortic valve(BAV) with aortic regurgitation(AR).Methods:From August 2021 to November 2024, a total of 298 consecutive patients with BAV-AR underwent aortic valve anatomic repair(AVr) in Shanghai Zhongshan Hospital Fudan University, 266 males and 32 females, with age of 39(29.5, 48.5) years. All patients underwent " four-step" three-dimensional anatomic repair of the aortic annulus and leaflets, 129(43.3%) patients via upper mini-sternotomy and 169(56.7%) patients via conventional median sternotomy, with the main steps including: (1) deep dissecting and annuloplasty of the virtual basal ring(VBR); (2) symmetrical repairing of leaflets; (3) replacement or remodeling of the sinus of Valsalva; (4) annuloplasty of the sinotubular junction(STJ). Basal and perioperative data were retrospectively collected, and statistical analysis was performed in conjunction with follow-up data.Results:All patients successfully underwent anatomical repair without transferring to valve replacement during operation. Among them, 43 patients underwent aortic root reimplantation technique(Reimplantation group), while 255 patients underwent modified aortic root sleeve remodeling technique(Sleeve group). The median cardiopulmonary bypass time for the Reimplantation and Sleeve groups were 154(134, 169) minutes and 111(95, 129) minutes, respectively( P<0.05); the median aortic cross-clamp time were 112(100, 131) minutes and 80(67, 94) minutes, respectively( P<0.05). Preoperative TEE showed 35 patients(81.4%) and 229 patients(89.8%) with moderate and severe AR in Reimplantation and Sleeve groups, respectively. Postoperative TEE showed 41 patients(95.3%) with no/trace AR and 2 patients(4.7%) with central mild AR in Reimplantation group, while 212 patients(83.1%) with no/trace AR and 43 patients(16.9%) with central mild AR in Sleeve group. Follow-up was completed in all patients, with a median follow-up of 12.9(4.7, 21.2) months. Echocardiography was obtained in 271 patients(90.9%) at the latest follow-up, including no/trace AR in 167 patients(56.0%), mild AR in 89 patients(29.9%), moderate AR in 14 patients(4.7%), and severe AR in 1 patient(0.3%). Conclusion:Aortic valve anatomic repair by standardized "four-step" approach is safe and reproducible. Satisfied short- and mid-term outcome have obtained in selected BAV-AR patients.

OBJECTIVE: To report the blood group antigen and antibody specificity identification methods for a patient with high-frequency antibodies, and the process of finding and providing compatible blood for the patient. METHODS: A patient sent from the Blood Transfusion Department of Shanxi Provincial People's Hospital to Blood Transfusion Technology Research Laboratory of Taiyuan Blood Center in November 2022 was selected for the study. Classical serological methods were used to determine the patient's blood type, screen for unexpected antibodies, identify antibodies, and perform crossmatching. High-frequency antibody identification was carried out using red blood cells treated with various enzymes. Blood group genotyping was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) and Sanger sequencing. Multiple strategies were employed to address the patient's blood source problem. The study was approved by the Medical Ethics Committee of Taiyuan Blood Center [Ethics No. 2024 Ethics Review No.(2)]. RESULTS: The patient's blood type was B, RhD positive. Initial screening of the patient's serum with multiple screening cells and antibody identification cells in saline medium was negative, but positive in antiglobulin medium. The patient's serum showed varying reaction intensities with red blood cells treated with different enzymes. MALDI-TOF mass spectrometry and Sanger sequencing revealed a homozygous nonsense variant c.376C>T (p.Gln126Ter) in the ABCG2 gene, resulting in the Jr(a-) phenotype. During family donor selection, the patient's son was found to have a heterozygous variant c.376C>T (p.Gln126Ter), and another heterozygous variant c.421C>A (p.Gln141Lys), which predicted a Jr(a+w) phenotype. Crossmatch tests confirmed the compatibility of blood from the patient's son, which was used to address the urgent blood requirement. Later, rare blood from a Jr(a-) donor from the Guangzhou Blood Center was used for the patient's ongoing treatment, saving the patient's life. CONCLUSION Combining classic serological testing with blood group gene typing techniques successfully identified the rare Jr(a-) blood type and high-frequency anti-Jra antibodies. Enzyme-treated red blood cell identification methods confirmed the presence of anti-Jra antibodies. By searching within the family and seeking help from other blood centers, compatible blood was found. This approach may provide insights for resolving similar complex blood matching problems in the future.
Humans ; Blood Grouping and Crossmatching/methods* ; Blood Group Antigens/immunology* ; Blood Transfusion ; Male ; Isoantibodies/blood* ; Female ; Genotype

Objective:To investigate the effect of abdominal circumference on intestinal radiation dose volume and acute intestinal toxicity in pelvic intensity modulated radiation therapy for rectal cancer.Methods:A total of 150 patients with locally advanced rectal cancer (LARC) who received adjuvant and neoadjuvant concurrent chemoradiotherapy at the Affiliated Cancer Hospital of Guizhou Medical University from March 2023 to January 2025 were enrolled, including 82 cases of adjuvant radiotherapy and 68 cases of neoadjuvant radiotherapy. All patients underwent radiotherapy CT simulation positioning in the standard mode of prone position with abdominal board padding and bladder filling. Intestinal toxicity was categorized as a binary variable based on the occurrence of ≥2 grade acute intestinal toxicity. Linear and logistic regression models were used to analyze the factors influencing intestinal radiation dose volumes (V 10, V 20, V 30, V 40) and acute intestinal toxicity in LARC patients. Generalized additive models and piecewise linear and logistic regression analyses were employed to examine the threshold effects of abdominal circumference on intestinal radiation dose volumes and acute intestinal toxicity. The threshold value for abdominal circumference was determined based on the upper limit of the 95% CI for the threshold. A difference test was used to validate the differences in intestinal radiation dose volume and acute intestinal toxicity between small and medium-to-large abdominal circumferences. Results:Univariate analysis showed that, gender, body mass, abdominal circumference, planning target volume (PTV), intestinal volume were all influencing factors for the radiation dose volumes (V 10, V 20, V 30, V 40) of each intestinal segment of patients with LARC undergoing adjuvant radiotherapy (all P<0.05). Body mass, abdominal circumference, intestinal volume were all influencing factors for the radiation dose volumes (V 10, V 20, V 30, V 40) of each intestinal segment of patients with LARC undergoing neoadjuvant radiotherapy (all P<0.05). Body mass index (BMI), abdominal circumference, intestinal volume and individual intestinal radiation volumes (V 10, V 20, V 30, V 40) were all influencing factors for the acute intestinal toxicity of patients with LARC undergoing adjuvant radiotherapy (all P<0.05). Body mass, BMI, abdominal circumference, multiple intestinal radiation dose volumes (V 20, V 30, V 40) were all influencing factors for the acute intestinal toxicity of patients with LARC undergoing neoadjuvant radiotherapy (all P<0.05). Multivariate analysis showed that, abdominal circumference (V 10: β=-1.01, 95% CI: -1.68--0.33, P=0.004; V 20: β=-0.94, 95% CI: -1.28--0.60, P<0.001; V 30: β=-0.58, 95% CI: -0.82--0.34, P<0.001; V 40: β=-0.41, 95% CI: -0.60--0.23, P<0.001) was an independent influencing factor for the radiation dose volume of each intestinal segment of patients with LARC undergoing adjuvant radiotherapy. Abdominal circumference (V 10: β=-0.92, 95% CI: -1.62--0.22, P=0.010; V 20: β=-0.84, 95% CI: -1.11--0.57, P<0.001; V 30: β=-0.42, 95% CI: -0.57--0.28, P<0.001; V 40: β=-0.30, 95% CI: -0.41--0.19, P<0.001) was an independent influencing factor for the radiation dose volume of each intestinal segment of patients with LARC undergoing neoadjuvant radiotherapy. Abdominal circumference ( OR=0.86, 95% CI: 0.78-0.95, P=0.002) was an independent influencing factor for the acute intestinal toxicity of patients with LARC undergoing adjuvant radiotherapy. Abdominal circumference ( OR=0.87, 95% CI: 0.79-0.96, P=0.004) was an independent influencing factor for the acute intestinal toxicity of patients with LARC undergoing neoadjuvant radiotherapy. The generalized additive model revealed a nonlinear relationship between abdominal circumference and intestinal radiation dose volume and acute intestinal toxicity of adjuvant radiotherapy patients. Further segmented regression analysis results showed that there was a threshold effect between abdominal circumference and intestinal radiation dose volume (V 10, V 20, V 30, V 40) and acute intestinal toxicity. The inflection point values between abdominal circumference and intestinal radiation dose volume V 10, V 20, V 30, V 40 in LARC patients undergoing adjuvant radiotherapy were all 71.9 cm; the inflection point values between abdominal circumference and the intestinal radiation dose volume V 10, V 20, V 30, V 40 in LARC patients undergoing neoadjuvant radiotherapy were 69.0, 69.0, 69.0, 68.6 cm, respectively; The inflection point values between abdominal circumference and acute intestinal toxicity in LARC patients undergoing adjuvant radiotherapy and neoadjuvant radiotherapy were 71.9, 69.0 cm, respectively. Based on the upper limit of the 95% CI threshold, the cutoff values for small and medium-to-large abdominal circumferences for patients undergoing adjuvant and neoadjuvant radiotherapy were set at 76.1, 71.9 cm, respectively. In patients undergoing adjuvant radiotherapy, the levels of intestinal radiation dose volume V 10 [ (7.65±2.29) cm 3vs. (5.88±2.68) cm 3, t=2.76, P=0.007], V 20 [ (4.28±1.27) cm 3vs. (2.72±1.31) cm 3, t=4.81, P<0.001], V 30 [ (2.42±1.07) cm 3vs. (1.37±0.76) cm 3, t=4.95, P<0.001], V 40 [ (1.69±0.74) cm 3vs. (0.92±0.58) cm 3, t=4.93, P<0.001] in the small abdominal circumference group ( n=22) were significantly higher than those in patients with medium-to-large abdominal circumferences ( n=60) ; In patients undergoing neoadjuvant radiotherapy, patients with small abdominal circumferences ( n=11) had significantly higher V 20 [ (3.09±0.84) cm 3vs. (2.28±1.17) cm 3, t=2.17, P=0.033], V 30 [1.44 (1.22, 1.53) cm 3vs. 0.91 (0.56, 1.22) cm 3, Z=-3.04, P=0.002], V 40 [0.93 (0.84, 1.09) cm 3vs. 0.44 (0.30, 0.81) cm 3, Z=-3.19, P=0.001] than patients with medium-to-large abdominal circumferences ( n=57). In patients receiving adjuvant radiotherapy and neoadjuvant radiotherapy, there were statistically significant differences in acute intestinal toxicity between patients with small abdominal circumferences and with medium-to-large abdominal circumferences ( χ2=10.46, P=0.001; χ2=8.13, P=0.004) . Conclusions:In the standard mode (prone position with abdominal board padding and bladder filling), abdominal circumference is an independent factor influencing the intestinal radiation dose volume and acute intestinal toxicity in rectal cancer radiotherapy patients. There is a significant non-linear threshold effect between abdominal circumference and different levels of intestinal radiation dose volume and acute intestinal toxicity. The impact of abdominal circumference on intestinal radiation dose volume and toxicity differs significantly before and after the inflection point value. Patients with smaller abdominal circumferences not only fail to achieve the expected benefits under the current standard radiotherapy regimen but also face higher risks of intestinal radiation dose volume and toxicity.

OBJECTIVE: To explore the application value and clinical effect of 3D printing combined with customized bone plate in the treatment of acetabular fracture. METHODS: From June 2020 to June 2022, 11 patients with acetabular fractures underwent preoperative planning using 3D printing technology and were treated with customized bone plates including 8 males and 3 females, aged 25 to 66 years old. The fractures were classified according to Letournel-Judet:4 posterior wall fractures, 2 T-type fractures, 2 transverse posterior wall fractures, 2 double column fractures, and 1 anterior column with posterior semi-transverse fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, postoperative drainage volume, postoperative fracture healing time, and hip function score were recorded and analyzed. RESULTS: The operation time of 11 patients was 80 to 150 min, intraoperative blood volume was 150 to 700 ml, fluoroscopy frequency was 2 to 6, postoperative drainage flow was 60 to 195 ml, and the fracture healing time was 2.5 to 6.0 months. Fracture reduction was evaluated according to Matta score:anatomical reduction in 3 cases and satisfactory reduction in 8 cases. Eleven patients were followed up for 7 to 18 months. The hip Merle d'Aubigne function scores were excellent in 6 cases, good in 3 cases, fair in 1 case and poor in 1 case. Incision fat liquefaction occurred in 1 case and obturator nerve traction in 1 case. CONCLUSION The application of 3D printing technology combined with customized bone plates in the treatment of acetabular fracture is effective. In addition, the printed model can provide the operator with the results of the three-dimensional shape of the fracture, which is convenient for surgical reduction and effectively improves the efficiency of surgery.
Humans ; Female ; Male ; Middle Aged ; Acetabulum/surgery* ; Printing, Three-Dimensional ; Adult ; Aged ; Bone Plates ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods*

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*