Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Statistical analysis was conducted on the quantity of Chinese medicine material and sliced herbal medicine,the species types and medicinal parts of Chinese medicine material and sliced herbal medicine,and the quantity and composition of Chinese patent medicines and single-herb preparations in Chinese Pharmacopoeia of the 2020 edition.The statistical results are available on the web site(http://itcm.hzau.edu.cn/yd/zgyd.htm)for reference.The analysis results showed that:(1)Chinese Pharmacopoeia(Part I)contained a total of 616 kinds of Chinese medicine material and sliced herbal medicine and 47 kinds of plant oils and extracts.The 616 kinds of Chinese medicine material and sliced herbal medicine originated from plants,animals,minerals,microorganisms,artificial or synthetic raw materials,human-sourced products,and products having the origin of both animal and plants.Of the 47 kinds of plant oils and extracts,46 were made from plant sources,and the remaining one,i.e.Cornu Bubali concentrated powder,was made from the animal sources.(2)A total of 421(73.60%)from the 616 kinds of Chinese medicine material and sliced herbal medicine originated from the single species,96(16.78%)originated from 2 kinds of species,40(6.99%)originated from 3 kinds of species,11(1.92%)originated from 4 kinds of species,2(0.35%)originated from 5 kinds of species,and 2(0.35%)originated from 6 kinds of species.Of the 47 kinds of plant oils and extracts,34 originated from the single species,5 originated from 2 kinds of species and 5 originated from 3 kinds of species.(3)The Chinese Pharmacopoeia(Part I)contained a total of 1 605 Chinese patent medicines and single-herb preparations.Except that the composition of Yunnan Baiyao Powder and Yunnan Baiyao Capsules was not issued,the remaining 1 603 types of Chinese patent medicines and single-herb preparations involved a total of 14 329 kinds of medicinal materials.The Chinese medicines with the leading 20 frequency used in the Chinese patent medicines and single-herb preparations recorded in the Chinese Pharmacopoeia of 2020 edition were Glycyrrhizae Radix et Rhizoma,Angelicae Sinensis Radix,Poria,Chuanxiong Rhizoma,Scutellariae Radix,Paeoniae Radix Alba,Astragali Radix,Citri Reticulatae Pericarpium,Rehmanniae Radix,Atractylodis Macrocephalae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Borneolum Syntheticum,Platycodonis Radix,Rhei Radix et Rhizoma,Rehmanniae Radix Preparata,Aucklandiae Radix,Carthami Flos,Ophiopogonis Radix,Codonopsis Radix and Angelicae Dahuricae Radix.The results suggest that there were still problems existing in Chinese Pharmacopoeia of the 2020 edition,i.e.,some of the drugs of Chinese patent medicines were not listed in the Chinese medicine material and sliced herbal medicine,and some of the prepared drugs of Chinese patent medicines were not listed in the Chinese medicine material and sliced herbal medicine,either.The systemic analysis of the general information of Chinese medicinal materials as well as their correlation with Chinese patent medicines in Chinese Pharmacopoeia will provide a reference for further research on the production of Chinese medicine material and sliced herbal medicine and the complete list of drugs in Chinese patent medicines.

Objective To standardize the management of clinical trials in our hospital,reduce the incidence of protocol deviations,and provide a reference for improving the quality of clinical trials.Methods The healthcare failure mode and effect analysis(HFMEA)method was used to determine the potential failure modes of the current protocol deviation.The frequency,severity and detectability of failure modes were quantified and evaluated.The risk priority number(RPN)was calculated and the corresponding improvement measures were proposed.The RPN values before and after the implementation of HFMEA were statistically analyzed to evaluate the improvement effect.Results After the implementation of HFMEA activities,the RPN values of 14 potential failure modes decreased significantly(P<0.05);The risk level of 12 potential failure modes decreased.The HFMEA team members'ability in finding and solving problems,communication and cooperation were significantly improved.Conclusions The implementation of HFMEA activities contributes to the management of protocol deviation in clinical trials,can effectively reduce the occurrence of protocol deviation,and provides experience for improving the quality of drug clinical trials.

Objective To study the relationship between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain in patients with hip osteoarthritis after hip arthroplasty.Methods The clinical data of 30 patients with facet joint-derived low back pain induced by hip osteoarthritis who underwent unilateral hip arthroplasty(observation group)from June 2019 to November 2020 in our hospital were retrospectively analyzed,and 50 healthy subjects who underwent lumbar X-ray examination in the physical examination center of our hospital at the same time were randomly selected as the control group.The sagittal spinopelvic parameters were measured based on the X-ray,including pelvic incidence(PI),pelvic tilt(PT),sacral slope(SS),lumbar lordosis(LL),sacrum pubic incidence(SPI)and sacrum pubic posterior angle(SPPA).The correlation between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain was analyzed by multiple linear regression,and its diagnostic efficacy to facet joint-derived low back pain was analyzed by receiver operating characteristic(ROC)curve.Results The PI,LL,SPI or SPA before and 1 year after surgery of the observation group had no significant difference combined with those of the control group(P>0.05).The PT before surgery of the observation group was smaller than that of the control group(P<0.05),and the SS before surgery was larger than that of the control group(P<0.05).Multiple linear regression analysis showed that PT and SS before surgery were correlated with facet joint-derived low back pain(P<0.05).The sensitivity of PT and SS before surgery in diagnosing facet joint-derived low back pain were 50.00%and 73.30%,with the specificity of 88.00%and 78.00%,respectively.ROC curve analysis showed that the area under the curve of PT and SS before surgery in diagnosing facet joint-derived low back pain were 0.708(95%CI:0.595 to 0.822)and 0.775(95%CI:0.673 to 0.877),respectively.Conclusion Patients with hip osteoarthritis pain have significantly larger SS and significantly smaller PT.Hip arthroplasty can alleviate the symptoms of low back pain without affecting the sagittal spinopelvic balance;the PT and SS before surgery are correlated with the facet joint-derived low back pain,and they are of high value in the diagnosing facet joint-derived low back pain.

Objective:To establish a method for obtaining planning target volume (PTV) and planning risk volume (PRV) margins caused by rotation in the use of adapt-to-position (ATP) modality of magnetic resonance linear accelerator (MRL) for patients with intracranial tumors.Methods:Clinical data of 6 patients with intracranial tumors (150 fractions in total) who received MRI-guided online ATP radiotherapy in Peking Union Medical College Hospital from November 2023 to January 2024 were retrospectively analyzed. The pre-planned CT structure was copied onto each segmented MR image and then the structures were traced back to the CT image according to the three-dimensional registration relationship. The anisotropic distance of the structure based on the original CT structure was calculated to obtain the variation range of the target and the organs at risk. The maximum anisotropic value was taken as the result of the PTV and the relationship between the results and intracranial location of different patients was analyzed. Group comparison was performed by Chi-square test. Two group comparison was conducted by post-hoc Wilcoxon signed-rank test. Results:After the rotation deviation was included, the range of target changes in the six directions of left and right (L/R), anterior and posterior (A/P) and superior and inferior (S/I) of the 6 patients were: (1.24± 0.86) mm/(1.91± 1.07) mm, (2.02± 1.26) mm/(1.66± 1.07) mm, (1.84± 1.84) mm /(2.94±1.93) mm, respectively. The results in the SI direction were significantly different, and the values in the I direction in 2 patients exceeded 4 mm, the margins suitable for all patients were 3.01 mm/2.4 mm(A/P), 1.9 mm/2.93 mm(L/R) and 3.14 mm/4.62 mm(S/I) in different directions, respectively. The L/R direction of the lens and the S/I direction of the optic nerve were significantly changed, and the A/P direction of the brain stem was (3.99± 4.64) mm. Larger values might be required when the target was in the posterior brain (left-down area, right-down area).Conclusions:The rotation deviation, organ movement and intracranial location affect the PTV and the organs at risk PRV in the MRI-guided ATP modality in intracranial tumors patients. The margin generation method based on image fusion can help to quantify the margin value reasonably.

Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.

Objective: To investigate the associations between neutrophil-to-lymphocyte ratio (NLR) and estimated glomerular filtration rate (eGFR) in patients with primary aldosteronism (PA). Methods: This study was a cross-sectional study. Consecutive patients diagnosed with PA and admitted to the Second Affiliated Hospital of Nanchang University from October 2017 to April 2022 were enrolled. General information, blood routine, renal function, and other clinical data of the patients were collected. Based on the median NLR of the enrolled patients, NLR-1·1.73 m^-2. Multiple linear regression and multivariate logistic regression models, smooth curve fitting and threshold effect exploration were used to analyze the relationship between NLR and eGFR in PA patients, and stratified analysis and interaction tests were used to evaluate potential variables that may affect the correlation between NLR and eGFR. Results: This study finally included 743 PA patients, aged (50.3±10.4) years, 42.9% (319/743) were female, and the median NLR was 2.3. After adjusting for sex, age, body mass index (BMI) and other factors, multiple linear regression analysis showed that high NLR was negatively correlated with eGFR (β=-4.9, P=0.008), and multivariate logistic regression analysis showed that high NLR was associated with low eGFR (OR=3.1, P=0.002). In the corrected smooth curve, NLR is U-shaped correlation with eGFR, and the inflection point is at NLR=3.5. When the NLR was<3.5, the eGFR decreased with the increase of NLR (corrected β=-4.7, P<0.001); When the NLR was≥3.5, the eGFR increased with the increase of NLR (corrected β=5.8, P=0.031). The results of stratified analysis showed that there was an interaction between the association of NLR and eGFR with the presence or absence of hyperlipidemia (P interaction=0.017), and the correlation between NLR and eGFR was stronger in PA patients with hyperlipidemia. Conclusion: In the PA patients, there is a U-shaped relationship between NLR and eGFR, and higher NLR is associated with lower eGFR. PA patients with elevated NLR should undergo additional screening for chronic kidney disease and receive related preventive interventions.
Humans ; Female ; Male ; Neutrophils ; Glomerular Filtration Rate ; Cross-Sectional Studies ; Lymphocytes ; Hyperaldosteronism/diagnosis* ; Hyperlipidemias

OBJECTIVE: To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA. METHODS: The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed. RESULTS: A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3^rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ²=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034). CONCLUSIONS Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.
Humans ; Carbapenems/therapeutic use* ; Pseudomonas aeruginosa ; Soft Tissue Infections/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Hematologic Diseases ; Survival Analysis

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications

OBJECTIVE: To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer. METHODS: Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 µg/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay. RESULTS: Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G₁/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05). CONCLUSION Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.
Humans ; Animals ; Mice ; Oldenlandia/metabolism* ; Proliferating Cell Nuclear Antigen ; Stomach Neoplasms ; Flavonoids/pharmacology* ; Reactive Oxygen Species/metabolism* ; Mice, Nude ; Ki-67 Antigen ; Cell Line, Tumor ; Apoptosis ; Plant Extracts/pharmacology* ; Caspases ; Cell Proliferation