ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.

ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.
COVID-19 ; Child ; Child, Preschool ; China ; Hospitals, Pediatric ; Humans ; SARS-CoV-2

Objective: To explore the effect of vaccination on viral negative conversion of children with COVID-19. Methods: A retrospective cohort study was conducted. A cohort of 189 children aged 3-14 years with COVID-19 admitted to Renji Hospital (South branch) of Shanghai Jiao Tong University School of Medicine from April 7^th to May 19^th 2022 was enrolled in the study. According to the vaccination status, the infected children were divided into an unvaccinated group and a vaccinated group. Age, gender, severity, clinical manifestations, and laboratory tests, etc. were compared between groups, by rank sum test or chi-square test. The effects of vaccination on viral negative conversion were analyzed by a Cox mixed-effects regression model. Additionally, a questionnaire survey was conducted among the parents of unvaccinated children to analyze the reasons for not being vaccinated. Results: A total of 189 children aged 3-14 years were enrolled, including 95 males (50.3%) and 94 females (49.7%), aged 5.7 (4.1,8.6) years. There were 117 cases (61.9%) in the unvaccinated group and 72 cases (38.1%) in the vaccinated group. The age of the vaccinated group was higher than that of the unvaccinated group (8.8 (6.8, 10.6) vs. 4.5 (3.6, 5.9) years, Z=9.45, P<0.001). No significant differences were found in clinical manifestations, disease severity, and laboratory results between groups (all P>0.05), except for the occurrence rate of cough symptoms, which was significantly higher in the vaccinated group than in the non-vaccinated group (68.1% (49/72) vs. 50.4% (59/117),χ²=5.67, P=0.017). The Kaplan-Meier survival curve and Cox mixed-effects regression model showed that the time to the viral negative conversion was significantly shorter in the vaccinated group compared with the unvaccinated group (8 (7, 10) vs. 11 (9, 12) d, Z=5.20, P<0.001; adjusted HR=2.19 (95%CI 1.62-2.97)). For questionnaire survey on the reasons for not receiving a vaccination, 115 questionnaires were distributed and 112 valid questionnaires (97.4%) were collected. The main reasons for not being vaccinated were that parents thought that their children were not in the range of appropriate age for vaccination (51 cases, 45.5%) and children were in special physical conditions (47 cases, 42.0%). Conclusion: Vaccination can effectively shorten the negative conversion time of children with COVID-19 and targeted programs should be developed to increase eligible children's vaccination rate for SARS-CoV-2 vaccination.
Child ; Female ; Male ; Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines ; Retrospective Studies ; SARS-CoV-2 ; China/epidemiology* ; Vaccines

Objective:To use a self-developed, prefabricated cap for making interocclusal records in implant-supported fixed prosthetic treatment, and to evaluate its effect of clinical application and accuracy of transferring intra-oral intercuspal position.Methods:Series of prefabricated caps for occlusal recording of implant-supported fixed prostheses were designed based on the healing abutments, and fabricated with three-dimensional (3D) printing. According to the inclusion and exclusion criteria, 12 partially edentulous patients who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology between November 2020 and September 2021, had lost no fewer than 2 contiguous teeth in distal extension (Kennedy Class Ⅰ or Ⅱ), and had received implant placement 3 months ago were enrolled. Self-control study design was used. Two occlusal records of each included case were obtained by the following 2methods:for the test group, appropriate prefabricated caps were used; and for the control group, polyvinyl siloxane occlusal record was directly set on the healing abutments. The working casts were mounted on the mechanical articulator using the 2 groups of occlusal records successively. Accuracy of occlusal relationship of the mounted casts was evaluated. Diagnostics test was performed to obtain the sensitivity and positive predictive value, which were determined in photographs by comparing the intra-oral occlusal contact points with those in the mounted casts, point-by-point. Virtual casts were taken by intraoral and extraoral scans in intercuspal position and imported to Geomagic Studio 2014. Then the root mean square values of occlusal clearance space between the upper and lower occlusal surfaces of remaining posterior teeth, and the deviations of the interocclusal position of the occlusal surfaces of the remaining teeth in the mandibular arches when superimposing the maxillary arches of the intraoral and extraoral scans were calculated. As a self-control design, paired t test was used. Results:Twelve participants were enrolled, including 3 men and 9 women aged (52.6±12.1) years, and 36 missing teeth. The prefabricated caps could fit on the healing abutments with good retention and stability. The sensitivity of the test group (0.73±0.14) was significantly better than that of control group (0.63±0.12, P<0.01), with no significant difference in positive predictive value between the 2 groups ( P>0.05). The deviations of the interocclusal position of the occlusal surfaces of the remaining teeth were (357.0±140.2) μm for the test group, and (399.4±206.3) μm for the control group, with no significant difference between them ( P>0.05). Conclusions:Interocclusal position record based on prefabricated cap in this study for implant-supported fixed prosthetic treatment can improve the consistency between the intra-oral occlusion and the occlusion in dental casts. This technique has good accuracy, clinical convenience and usability.

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial ow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.
Aged ; Betacoronavirus ; isolation & purification ; Cannula ; Coronavirus Infections ; therapy ; Humans ; Oxygen ; administration & dosage ; Pandemics ; Pneumonia, Viral ; therapy

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 infection. Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial flow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.
Aged ; Betacoronavirus ; Cannula ; Coronavirus Infections ; complications ; therapy ; Humans ; Hypoxia ; etiology ; prevention & control ; therapy ; Masks ; Oxygen ; administration & dosage ; Oxygen Inhalation Therapy ; instrumentation ; standards ; Pandemics ; Pneumonia, Viral ; complications ; therapy

Objective To evaluated the pharmacokinetics and safety of single microdose imatinib mesylate in Chinese health volunteers.Methods Eight subjects were randomly assigned to take orally a single microdose of 4 mg imatinib mesylate.The serum concentrations of ima-tinib were assayed with LC-MS/MS.Results The following pharmaco-kinetic parameters were calculated by WinNolin 6.3 software.Cmax (12.70 ±6.61 ) ng · mL-1, tmax ( 1.94 ±0.94 ) h, AUC0-24 h (90.10 ±37.70)ng· mL-1· h, t1/2 ( 10.40 ± 5.01 ) h, CL/F (47.20 ±33.40)L· h-1, V/F ( 541.00 ± 128.00 ) L, MRT (7.21 ±1.30)h.No adverse events and serious adverse events were detected.Conclusion Pharm-acokinetic parameters of phase 0 research of imatinib mesylate reflected the characteristics of the drug distribution and elimination in some extent.It was significant to protect subjects in phase 0 research by taking microdose imatinib mesylate.