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This study establishes and optimizes the physiologically based pharmacokinetics (PBPK) model for dapagliflozin, predicts the drug distribution into relevant tissues, and calculates the inhibitory effect on the sodium-glucose cotransporters (SGLTs) in the intestine and renal proximal tubule. Based on literature data, a PBPK model for oral administration in healthy adults was established and the predicted blood concentration-time curve characteristics, the main pharmacokinetic parameters (PK), and drug excretion in urine were compared with the published data. To verify and optimize the model and verify the accuracy of the tissue distribution and concentration predictions, a pharmacodynamics model (PD) was established. Urine glucose excretion (UGE) was simulated at the corresponding times. The characteristics of the drug-time curve predicted by the model are similar to those of the measured curve, and the ratio of the main PK parameters to the measured values is within a two-fold range; the accuracy of the established PBPK model is good. The maximal inhibition obtained with 10 mg of dapagliflozin on the duodenum and jejunum segment sodium-glucose co-transporter 1 (SGLT1s) was 1.6%-4.7%, and the inhibition rate of the sodium-glucose co-transporter 2 (SGLT2s) in the proximal tubule of the kidney was as high as 99.9%. At a dose of 10 mg, dapagliflozin delayed intestinal glucose absorption while occupying most of the sites (99.9%) of the renal sodium-glucose cotransporter 2 and inhibiting its glucose reabsorption. This physiological-pharmacokinetic model for dapagliflozin in healthy adults can provide meaningful guidance for exploring pharmacological mechanisms and potential toxicity of gliflozin by simulating drug distribution in different tissues.
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OBJECTIVE@#To assess the clinical efficacy of minimally invasive technology with trajectory screw fixation for fragility fractures of pelvic(FFP).@*METHODS@#A retrospective case control study was performed to analyze the clinical data of 35 patients with FFP who were treated and followed up between January 2016 and December 2019. There were 12 males and 23 females, aged from 65 to 99 years with an average of(75.4±7.8) years old. There were 13 cases of type Ⅱb, 7 cases of type Ⅱc, 8 cases of type Ⅲa, 2 cases of type Ⅲb, 2 cases of type Ⅲc, 1 case of type Ⅳb, and 2 cases of type Ⅳc according to Rommens FFP comprehensive classification. All patients received the treatment of minimally invasive technology with trajectory screws fixation. According to the different methods of anterior pelvic ring fixation, FFP patients were divided into two groups:12 cases were fixed with the pedicle screw rod system in the anterior pelvic subcutaneous internal fixator (INFIX) group;23 cases were fixed with hollow screws of the pubic symphysis, superior ramus of pubis or acetabular anterior column in the screw group. The operation time, intraoperative blood loss, intraoperative fluoroscopy times, length of hospital stay, cost of internal fixation, pre- and post-operative visual analogue scale(VAS) were compared between the two groups. The fracture reduction quality was evaluated according to the Matta criteria, and the clinical function was evaluated by the Majeed functional scoring system respectively.@*RESULTS@#All patients were followed up for 12 to 39(16.5±5.4) months after surgery. There was no statistically significant difference in the operation time, intraoperative blood loss, intraoperative fluoroscopy time, and length of hospital stay between the two groups(P>0.05). As for the cost of internal fixation, the cost of internal fixation in the screw group [2 914 (2 914, 4 371) yuan] was significantly lower than that of the INFIX group [6 205 (6 205, 6 205) yuan] (P<0.05). No significant difference was observed in the incidence of postoperative complications between the two groups (P>0.05). There was no significant difference in VAS assessment at admission, 1 week, and 3 months after surgery between the two groups(P>0.05). However, the VAS assessment at 1 week and 3 months after surgery of the two groups were significantly better than those at admission(P<0.05). There was no significant difference in the quality of fracture reduction after the operation and the efficacy evaluation at the last follow-up between the two groups(P>0.05).@*CONCLUSION@#For the treatment of fragility fractures, minimally invasive technology with trajectory screw fixation can achieve good clinical efficacy. It has the advantages of being relatively minimally invasive, less bleeding, relieving the pain. It deserves clinical application.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Blood Loss, Surgical , Case-Control Studies , Fractures, Bone/surgery , Pelvic Bones/surgery , Retrospective StudiesABSTRACT
OBJECTIVE@#To evaluate the efficacy of iliolumbar fixation in the treatment of U-shaped sacral fractures.@*METHODS@#A retrospective study was conducted on the 14 complex U-shaped sacral fractures which had been treated from January 2014 to December 2019, involved 10 males and 4 females, aged 24 to 48 (35.4±6.5) years. Fracture healing time, nerve function, clinical function and complications were observed in the patients.@*RESULTS@#All patients were followed up for 9 to 16(26.0±5.9) months. The complete weight-bearing time for bone healing was(12.4±2.0) weeks. One case of surgical incision infection occurred after operation, and one case of sacrum nailspenetrated to the outer plate of sacrum. No complications such as pressure ulcers, loosening or rupture of internal fixation occurred. According to Gibbons scoring, the neurological function recovered from preoperative 2.9±0.9 to postoperative 2.1±1.1, there were statistically significant differences between preoperative and postoperative (@*CONCLUSION@#Sacral lumbar fixation is an effective method for the treatment of U-shaped sacrum fractures. It has the advantages of strong internal fixation and satisfactory functional recovery.
Subject(s)
Female , Humans , Male , Bone Screws , Fracture Fixation, Internal , Retrospective Studies , Sacrum/surgery , Spinal Fractures/surgery , Treatment OutcomeABSTRACT
PURPOSE@#It is a challenge for the primary hospitals to manage multiple trauma patients. In this article, we explored the advantage of establishing a surgical intensive care unit (SICU) predominant by cardiothoracic surgeons in the early management of multiple trauma.@*METHODS@#This was a retrospective study and patients with multiple trauma in our hospital were collected and divided into two groups, based on time period and treat modes: group A (retrospective observation group) where patients were treated with the traditional treatment mode from January 2017 to December 2017 and group B (study group) where patients were treated in the SICU predominant by cardiothoracic surgeons from January 2018 to December 2018. Clinical data including demographics, injury severity score (ISS), causes of injury, time intervals from reception to entering SICU or operating room and mortality three days after injuries were collected. Data were analyzed by SPSS 20.0 software. Categorical variables were presented as number and/or frequency and continuous variables as mean ± SD.@*RESULTS@#Altogether 406 patients were included in this study, including 217 patients in group A and 189 patients in group B. General data between the two groups revealed no significant difference: mean age (years) (35.51 ± 12.97 vs. 33.62 ± 13.61, p = 0.631), gender distribution (mean/female, 130/87 vs. 116/73, p = 0.589) and ISS (15.92 ± 7.95 vs. 16.16 ± 6.89, p = 0.698). Fall from height were the dominant mechanism of injury, with 135 cases in group A (71.4%) and 121 cases in group B (55.8%), followed by traffic accidents. Injury mechanism showed no significant differences between two groups (p = 1.256). Introduction of the SICU significantly improved the care of trauma patients, regarding speed and mortality. Time intervals between reception and entering SICU or operating room was (108.23 ± 6.72) min and (45.67 ± 7.96) min in group A and B, respectively (p = 0.001). Mortality three days after injuries was 13.89% and 5.53% in group A and B, respectively (p = 0.005).@*CONCLUSION@#Establishing a SICU predominant by cardiothoracic surgeons can reduce the early mortality rates in multiple trauma patients.
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Objective: To investigate the effects of a recombinant endoglin-macrophage inflammatory protein 3α Fc-fusion protein (EM) vaccine on tumor angiogenesis and growth in mice with H22 hepatocellular carcinoma. Methods: An in vivo hepatoma mouse model was established. Seven days after subcutaneous inoculation of H22 tumor cells, mice were randomly divided into four groups: EM, endoglin Fc-fusion protein, macrophage inflammatory protein 3α Fc-fusion protein, and normal saline groups. Tumor volume and survival rate of mice were studied at 3-day intervals. Microvessel density of the tumors and tumor cell proliferation were detected by immunohistochemistry, and tumor cell apoptosis was detected by TdT-mediated biotinylated-dUTP nick-end label staining. The number of CD11c and CD86 positive dendritic cells were detected by flow cytometry. Results: Compared with the other groups, the tumor volume became smaller, and the survival time was longer in the EM-treated group. Besides, microvessel density and cell proliferation index were significantly lower, while the tumor cell apoptosis index was significantly higher in the EM-treated group. Besides the number of CD11c and CD86 positive dendritic cells in EM-treated mice was larger than that in other groups. Conclusions: EM Fc-fusion protein could effectively inhibit tumor growth through inhibiting endoglin-related tumor angiogenesis and cell proliferation, promoting tumor cell apoptosis, and could induce a certain degree of antitumor immune responses.
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The diagnosis of osteochondral lesions of the talus can be based on the patients' symptoms, medical history, MRI, detailed physical examination and arthroscopy. Its treatment includes conservative treatment and surgical treatment. Conservative treatment includes rest, partial-weight bearing, plaster immobilization, wear the orthopedic support, take the non-steroidal anti-inflammatory drugs and so on. Conservative treatment is less risky and effective for mild injuries. Surgical treatment includes debridement, marrow stimulation, internal fixation and cartilage transplantation, autologous chondrocyte transplantation, articular cavity injection biological additions, ultrasonic and electromagnetic stimulation technology, tissue engineering technology, etc. Currently, there are various treatment methods, each with indications and advantages and disadvantages. Among these methods, the most commonly used ones are debridement, marrow stimulation, cartilage transplantation and autologous chondrocyte transplantation, and they deserve extensive promotion. Debridement and marrow stimulation are performed minimally traumatically under arthroscopy. The operation is simple and inexpensive with positive effects and mild pain. There is a higher rate of success for small-scale injuries, but if the operation fails, it will result in a wider range of defects, because of the fibrous cartilages formed after the operation. The cartilage transplantation can be performed in an one-stage operation. After the operation, the hyaline cartilage can be restored, but there are different levels of pathological changes in the donor sites. Chondrocytes transplantation can solve the problem of larger osteochondral defects left after the initial treatment failure, and the donor cartilage can be repaired without affecting the donor sites. But the disadvantages are its long time treatment, staged operations and higher cost. As far as all these treatments are concerned, recent treatment effects are satisfactory, but the long-term efficacy is still questionable. For the autologous chondrocyte transplantation and emerging tissue engineering treatment technology, there is still broad research prospect.
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<p><b>OBJECTIVE</b>To evaluate the clinical effects of over 5 year follow up of unilateral pedicle screw fixation with transforaminal lumbar interbody fusion(TLIF) in treating lumbar degenerative diseases.</p><p><b>METHODS</b>The clinical data of 24 patients with lumbar degenerative disease underwent unilateral pedicle screw fixation with transforaminal lumbar interbody fusion from March 2007 to October 2009, were retrospectively analyzed. There were 13 males and 11 females, aged from 34 to 68 years old with an average of 52 years. Postoperative pain and functional results were analyzed by the visual analogue scale(VAS) and Oswestry Disability Index(ODI). Radiological examination was obtained for each patient to assess the height of intervertebral space, postoperative intervertebral fusion conditions and general complications.</p><p><b>RESULTS</b>All patients were followed up from 5 to 8 years with an average of 6.7 years. VAS scores of low back pain and leg pain decreased from preoperative 7.82±0.71, 8.42±1.24 to postoperative 1.87±0.81, 2.23±1.62, respectively(<0.05). ODI decreased from preoperative(53.42±8.26)% to postoperative(12.45±7.67)%(<0.05). Postoperative intervertebral space height in different segments were improved than preoperative(<0.05), but in final follow up it was decreased than 3 months after operation(<0.05). There was no significant difference in the postoperative intervertebral space height between the operated side and non operated side. But at final follow up, the intervertebral space height of non operated side was obviously loss. At final follow up, the fusion rate was 95.8%. The incidence of adjacent segment degeneration was 45.8%. The paraspinal muscle fibrosis incidence was 8.3%. No complications such as secondary scoliosis, intervertebral height loss, cage slippage, screw loosening and internal fixation breakage were found.</p><p><b>CONCLUSIONS</b>Unilateral pedicle screw fixation with TLIF is a satisfactory method and can obtain good effects in treating lumbar degenerative diseases according to over 5 year follow up, however, its indications should be well considered. But the problems such as intervertebral space height of operated side loss and adjacent segment degeneration after unilateral pedicle screw fixation need further clinical study.</p>
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<p><b>OBJECTIVE</b>To develop a bioinformatic tool and to use it to identify proteomic patterns in serum, distinguishing colorectal cancer from colorectal adenoma and healthy individuals.</p><p><b>METHODS</b>182 serum samples including 55 colorectal cancer patients, 35 colorectal adenoma and 92 healthy individuals were subjected to analysis by surface-enhanced laser desorption/ionization (SELDI) mass spectrometry.</p><p><b>RESULT</b>The diagnostic pattern combined of 4 candidate biomarkers (M/Z 5911, 8922, 8 944, and 8817) could separate colorectal patients from healthy control with a specificity of 93.3%, sensitivity of 90.9%, and Youden index value of 0.84242. The diagnostic pattern combined of 7 candidate biomarkers (M/Z 17247, 18420 ,5911, 9294, 4654, 21694, and 21742) could separate colorectal cancer patients from colorectal adenoma patients with a specificity of 83.2%, sensitivity of 89.3%, and Youden index value of 0.72484.</p><p><b>CONCLUSION</b>Combination of SELDI with bioinformatics tool can identify some new biomarkers from the sera of colorectal cancer patients, which has a high sensitivity and specificity to distinguish colorectal cancer patients from healthy control.</p>