OBJECTIVE: To assess the effectiveness of the single Kocher-Langenbeck approach combined with anterograde channel screw technique for the treatment of acetabular transverse and posterior wall fractures. METHODS: Between March 2020 and October 2022, 17 cases of acetabular transverse and posterior wall fractures were treated with the single Kocher-Langenbeck approach combined with anterograde channel screw technique. There were 11 males and 6 females, with an average age of 53.6 years (range, 42-64 years). Causes of injury included traffic accident in 12 cases, and falling from height in 5 cases. The time from injury to operation ranged from 4 to 16 days with an average of 8.8 days. The operation time, intraoperative blood loss, and fluoroscopy frequency were recorded; X-ray films were reviewed regularly after operation to observe the fracture healing, and postoperative complications were recorded. At last follow-up, Matta score was used to evaluate the reduction of fracture, Harris score and modified Merle D'Aubigné-Postel scores system were used to evaluate the hip joint function. RESULTS: The operation time was 150-230 minutes (mean, 185.9 minutes), the intraoperative blood loss was 385-520 mL (mean, 446.2 mL), and the fluoroscopy frequency was 18-34 times (mean, 27.5 times). Postoperative fat liquefaction occurred in 1 case and the other incisions healed by first intention; 3 cases had limb numbness after operation, and the symptoms disappeared after active symptomatic treatment; no urogenital system and intestinal injury occurred. All patients were followed up 12-28 months (mean, 19.9 months). Bone union was achieved in all cases with an average healing time of 10.8 weeks (range, 8-14 weeks). There was no complication such as loosening and breakage of internal fixators. At last follow-up, according to Matta score, 12 cases achieved anatomic reduction, 3 satisfactory reduction, and 2 fair reduction, the satisfactory rate was 88.2%; according to Harris hip function score, 12 cases were excellent, 3 good, and 2 fair, the excellent and good rate was 88.2%; according to the modified Merle D'Aubign Aubigné-Postel scoring system, the results were excellent in 11 cases, good in 3 cases, and fair in 3 cases, with an excellent and good rate of 82.4%. CONCLUSION The single Kocher-Langenbeck approach combined with anterograde channel screw technique is a minimally invasive method for the treatment of acetabular transverse and posterior wall fractures with less complications, simple operation, and satisfactory effectiveness.
Male ; Female ; Humans ; Middle Aged ; Blood Loss, Surgical ; Fracture Fixation, Internal/methods* ; Treatment Outcome ; Fractures, Bone/surgery* ; Acetabulum/injuries* ; Bone Screws ; Hip Fractures/surgery* ; Retrospective Studies

Objective:To analyze the impact of cecal ligation and puncture (CLP)-induced sepsis on the proliferation and differentiation of intestinal epithelial cells.Methods:① Animal experiment: sixteen male C57BL/6 mice were divided into sham operation group (Sham group) and CLP-induced sepsis model group (CLP group) by random number table method, with 8 mice in each group. After 5 days of operation, the jejunal tissues were taken for determination of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and intestinal alkaline phosphatase (IAP) by polymerase chain reaction (PCR). The translation of LGR5 was detected by Western blotting. The expression of proliferating cell nuclear antigen (Ki67) was analyzed by immunohistochemistry. IAP level was detected by modified calcium cobalt staining and colorimetry. Immunofluorescence staining was used to detect the expression of Paneth cell marker molecule lysozyme 1 (LYZ1) and goblet cell marker molecule mucin 2 (MUC2). ② Cell experiment: IEC6 cells in logarithmic growth stage were divided into blank control group and lipopolysaccharide (LPS) group (LPS 5 μg/mL). Twenty-four hours after treatment, PCR and Western blotting were used to analyze the transcription and translation of LGR5. The proliferation of IEC6 cells were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining. The transcription and translation of IAP were detected by PCR and colorimetric method respectively.Results:① Animal experiment: the immunohistochemical results showed that the positive rate of Ki67 staining in the jejunal tissue of CLP group was lower than that of Sham group [(41.7±2.5)% vs. (48.7±1.4)%, P = 0.01]. PCR and Western blotting results showed that there were no statistical differences in the mRNA and protein expressions of LGR5 in the jejunal tissue between the CLP group and Sham group (Lgr5 mRNA: 0.7±0.1 vs. 1.0±0.2, P = 0.11; LGR5/β-actin: 0.83±0.17 vs. 0.68±0.19, P = 0.24). The mRNA (0.4±0.1 vs. 1.0±0.1, P < 0.01) and protein (U/g: 47.3±6.0 vs. 73.1±15.3, P < 0.01) levels of IAP in the jejunal tissue were lower in CLP group. Immunofluorescence saining analysis showed that the expressions of LYZ1 and MUC2 in the CLP group were lower than those in the Sham group. ②Cell experiment: PCR and Western blotting results showed that there was no significant difference in the expression of LGR5 between the LPS group and the blank control group (Lgr5 mRNA: 0.9±0.1 vs. 1.0±0.2, P = 0.33; LGR5/β-actin: 0.71±0.18 vs. 0.69±0.04, P = 0.81). The proliferation rate of IEC6 cells in the LPS group was lower than that in the blank control group, but there was no significant difference [positivity rate of EdU: (40.5±3.8)% vs. (46.5±3.6)%, P = 0.11]. The mRNA (0.5±0.1 vs. 1.0±0.2, P < 0.01) and protein (U/g: 15.0±4.0 vs. 41.2±10.4, P < 0.01) of IAP in the LPS group were lower than those in the blank control group. Conclusion:CLP-induced sepsis inhibits the proliferation and differentiation of intestinal epithelial cells, impairing the self-renewal ability of intestinal epithelium.

OBJECTIVE To establish a method for simultaneous determination of two third-generation anti-epileptic medicines such as lacosamide and perampanel in human plasma and apply this method in clinical practice. METHODS Using clozapine as internal standard， the concentrations of lacosamide and perampanel of plasma samples in 10 epileptic patients were determined by LC-MS/MS after protein precipitation with acetonitrile and dilution with acetonitrile-water （20∶80，V/V）， and the plasma minimum concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C18 column， with mobile phase A consisted of 10 mmol/L ammonium formate and mobile phase B consisted of methanol-acetonitrile-isopropanol （0.2% formic acid） mixed solution （7∶1.5∶1.5， V/V/V） for gradient elution at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning. The ion pair used for quantitative analysis of lacosamide， perampanel and internal standard were m/z 251.2→ 144.1， m/z 350.2→219.2 and m/z 327.2→270.0， respectively. RESULTS The linear ranges of lacosamide and perampanel were 0.001 25-0.125 μg/mL（r＞0.99）， 0.037 5-3.75 ng/mL （r＞0.99）； the limits of quantification were 0.001 25 μg/mL and 0.037 5 ng/mL， respectively. The precision and accuracy within and between batches， extraction recovery rate， matrix effect， and stability all met relevant requirements. The minimum concentrations of lacosamide in No. 1-5 patients were 5.3-12.2 μg/mL， and the minimum concentrations of perampanel in No.6-10 patients were 208-510 ng/mL， respectively. CONCLUSIONS The established method is simple， rapid and suitable for the therapeutic drug monitoring of lacosamide and perampanel.

Objective To rapidly evaluate the efficacy,safety and economics of empagliflozin in the treatment of type 2 diabetes mellitus(T2DM)and to provide evidence-based medical evidence for clinical decision.Methods PubMed,Embase,the Cochrane Library,CNKI,Wangfang,VIP database and major health technology assessment(HTA)websites were searched from the construction of the databases to Nov 30th,2022.Two researchers independently screened,extracted the data,evaluated the quality and analyzed the results according to inclusion and exclusion criteria.Results A total of 23 literatures were included,including 3 HTA reports,10 systematic review/Meta-analyses and 10 pharmacoeconomic studies.The results of efficacy showed that empagliflozin reduced HbA1c,blood pressure,body weight and all-cause mortality compared with the control group.Safety studies showed that empagliflozin was generally well tolerated,and significantly reduced MACEs and the relative risk of the renal primary outcomes,but increased the risk of genital infections and electrolyte abnormality compared with placebo and other oral antidiabetic drugs.The economic evaluation results showed that empagliflozin was more cost-effective in high risk patients with comorbid cardiovascular or kidney disease.Conclusion Empagliflozin is effective and safe in the treatment of T2DM,but the pharmacoeconomic studies focusing on chinese populations are urgently needed.

OBJECTIVE To sum marize the pro cedure and informatization construction of centralized volume-based procurement（VBP）in our hospital ，in order to give references for normal development of centralized VBP. METHODS The standardized workflow system was established ，including using flow chart method to establish standardized workflow ，carrying out procedure training and inspection of procedure implementation ， and continuously conducting procedure optimization. The information system was developed for the task links that needed a lot of calculation to improve the automation level of information processing. RESULTS & CONCLUSIONS Eight specific work procedures were established in our hospital ，including the work procedures of submitting the demand data of centralized VBP and the implementation of centralized VBP ，and has taken measures such as procedure training ，establishing supervision and inspection system and using auxiliary means to promote the implementation of the procedure ，so as to optimize the procedure and work form. An informatization platform for the clinical task allocation of the agreed purchase quantity of centralized VBP and a supervision platform for the daily use of VBP were also established in our hospital，then the two tasks with a large amount of calculation could be finished. Standardized workflow system and informatization platform construction has improved the operation and supervision efficiency of centralized VBP in our hospital ，ensured the completion of centralized purchase tasks and saved human resources ，which has a certain promotion value.

Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8⁺ T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/pathology* ; Carcinoma, Adenoid Cystic/pathology* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Humans ; Immunosuppression Therapy ; Interferon-gamma/pharmacology* ; Mouth Neoplasms/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Salivary Gland Neoplasms/pathology*

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

DNA methylation is a prevalent epigenetic modification in vertebrates, and it has been shown to be involved the regulation of gene expression and embryo development. However, it remains unclear how DNA methylation regulates sexual development, especially in species without sex chromosomes. To determine this, we utilized zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We reveal that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germ cell development, and the methylome of PGCs is reset to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When DNA methyltransferase (DNMT) activity in juveniles was blocked after 9 dpf, the zebrafish developed into females. We also show that Tet3 is involved in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMT activity can prevent the female-to-male sex transition, sug-gesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germ cell development and sexual plasticity.

Objective:To investigate the effects of dexmedetomidine on perioperative coagulation function and inflammatory factors in patients with malignant ovarian tumors.Methods:A total of 60 patients undergoing cytoreductive surgery for malignant ovarian tumors from September 2019 to May 2020 in the Second Hospital of Shanxi Medical University were selected and divided into the dexmedetomidine group and the control group according to the random number table method, 30 cases in each group. Patients in the dexmedetomidine group were pumped with dexmedetomidine 0.5 μg/kg 10 min before induction of anesthesia, and then the intravenous pump was maintained at a rate of 0.2-0.6 μg·kg -1·h -1 until 30 min before the completion of the operation pump injection. The control group was pumped with 0.9% NaCl solution of the same volume at the same time. Before induction of anesthesia (T 0), 2 h after administration (T 1), and 3 h after operation (T 2), the patients' venous blood was collected to detect platelet count (Plt), prothrombin time (PT), activated partial thrombin time (APTT), plasma fibrinogen (FIB), D-dimer; and levels of serum inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were also detected. The operation time, intraoperative fluid infusion, amount of anesthetics, and total intraoperative blood loss were compared between the two groups. Results:Plt at T 1 and T 2 time were (154±28)×10 9/L, (138±27)×10 9/L of the dexmedetomidine group and (133±44)×10 9/L, (114±50)×10 9/L of the control group, which were lower than those of both groups at T 0 time [(182±46)×10 9/L, (184±55)×10 9/L], and the differences were statistically significant ( F values were 11.975, 16.058, all P < 0.05); and Plt at T 1 and T 2 time of the control group were lower than those of the dexmedetomidine group (all P < 0.05). FIB level at T 1 and T 2 time [(3.2±0.9) g/L, (3.3±0.9) g/L of the dexmedetomidine group; (3.7±0.6) g/L, (4.6±0.9) g/L of the control group] and D-dimer level at T 1 and T 2 time [(0.77±0.25) mg/L, (0.81±0.51) mg/L of the dexmedetomidine group; (0.96±0.31) mg/L, (1.15±0.56) mg/L of the control group] were higher than those of both groups at T 0 time [FIB: (3.0met) g/L, (2.8 met) g/L; D-dimer: (0.65rt T) mg/L, (0.63 rt T) mg/L], and the differences were statistically significant (F values were 5.234, 46.121, 4.358, 11.091, all P < 0.05); FIB and D-dimer levels at T 1 and T 2 time of the control group were higher than those of the dexmedetomidine group (all P < 0.05). PT and APTT at T 2 time of the dexmedetomidine group were (12.7±0.5) s and (33.8±3.7) s, respectively, and the control group were (12.3±0.8) s, (31.8±2.4)s, respectively, which were shorter than those of both groups at T 0 time [PT: (13.0±0.3) s, (13.0±0.3) s; APTT: (35.7±2.0) s, (35.7±2.6) s], and the differences were statistically significant (all P < 0.05), and PT and APTT levels at T 2 time of the control group were shorter than those of the dexmedetomidine group (all P < 0.05). IL-6 level at T 1 and T 2 time [(73.3±2.8) pg/L, (84.7±3.8) pg/L of the dexmedetomidine group; (81.5±3.6) pg/L, (89.8±3.2) pg/L of the control group] and TNF-α level at T 1 and T 2 time [(27.4±4.4) ng/L, (32.9±3.7) ng/L of the dexmedetomidine group; (32.7±2.5) ng/L, (39.8±4.0) ng/L of the control group] were higher than those of both groups at T 0 time [IL-6: (65.9±2.9) pg/L, (65.0±1.8) pg/L; TNF-α: (15.4±3.1) ng/L, (16.6±2.6) ng/L)], and the differences were statistically significant ( F values were 264.650, 553.019, 162.447, and 438.225, respectively, all P < 0.05), and IL-6 and TNF-α levels at T 1 and T 2 time of the control group were higher than those of the dexmedetomidine group (all P < 0.05). There were no statistically significant differences in operation time, intraoperative fluid infusion, and intraoperative total blood loss between the two groups (all P > 0.05), but the intraoperative use of propofol and remifentanil of the control group was more than that of the dexmedetomidine group (all P < 0.05). Conclusion:Dexmedetomidine under general anesthesia for malignant ovarian patients undergoing surgery can effectively improve the perioperative coagulation function and reduce the level of inflammatory factors, thereby reducing the risk of postoperative thrombotic events.

Centralized drug procurement in large quantities is a major step to deepen the medical and healthcare system reform, to improve the mechanism of drug price formation, and to give full play to the role of medical insurance in guiding drug prices in China. Combined with the practice of centralized drug purchasing in public hospitals, the authors sorted out the practical problems and causes from four aspects which affected the implementation of centralized drug purchasing policy in public hospitals: selection on centrally purchased drugs, procurement and supply, clinical use, and hospital financial operation. On this basis, suggestions were put forward to provide reference for the normalization of centralized drug procurement work, such as coordinating national and regional drug collection policies, reasonably setting distribution costs, extending the agreed procurement period, and carrying out special evaluation for drug collection.