This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

The clinical practice guidelines of traditional Chinese medicine （TCM） have problems such as limited clinical application and unclear implementation effects， which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice， this article proposes a model of combining TCM guidelines with real-world study， which includes 4 steps. Firstly， during the implementation process of the guidelines， a high-quality research database is established. Secondly， the recommendations in the guidelines are evaluated based on the established database in multiple dimensions， including applicability， effectiveness， safety， and cost-effectiveness， and thus their effectiveness in practical applications can be determined. Thirdly， based on the established database， core prescriptions are identified， and the targeted populations and medication plans are determined. That is， the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies， dosages， and duration on efficacy. Fourthly， the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions， improving their application in clinical practice. Moreover， this model can reduce research costs and improve research efficiency. When applying this model， researchers need to pay attention to the quality of real-world evidence， ensuring that it can truly reflect the situation in clinical practice. In addition， importance should be attached to the clinical application of guideline recommendations， ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally， full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion， the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

BACKGROUND:The traditional fixation method for femoral neck fractures is three hollow screws inverted triangle fixation,and the optimal fixation method for femoral neck fractures that have not achieved anatomical reduction is inconclusive. OBJECTIVE:To compare the biomechanical properties of cannulated screws internal fixation for sub-capitated femoral neck fracture with different reduction qualities based on finite element analysis. METHODS:The three-dimensional digital model was reconstructed using CT data of the proximal femur from a healthy male volunteer.The femur was modeled to sub-capitated femoral neck fractures.Fracture models were divided into anatomical reduction group,coxa vara group,and coxa valgus group.All fracture model groups were transferred using the standard group,screw depression group,and screw elevation group.A vertical downward stress of 1 400 N was applied to the femoral head at the top of the acetabulum.The displacement and stress distribution of the femur and internal fixator under different fixation methods were observed,and the maximum stress and displacement of the femur and fixator were compared. RESULTS AND CONCLUSION:(1)For anatomical reduction femoral neck fracture,the peak stress of fixation in the standard group,screw depression group and screw elevation group was 41.35,31.27 and 43.32 MPa,respectively.The maximum peak stress of the femur was found on the screw elevation group(28.58 MPa),and the standard group had the maximum peak displacement.(2)During hip varus,the stresses in the three subgroups were relatively dispersed and even.The peak stress of the femur in the standard group was the smallest,but the peak displacement was the largest.The stability of fixation might be poor.The peak displacement of the femur in the screw depression group was the smallest.(3)In the hip valgus,obvious screw stress concentration appeared in the screw depression group,and the peak displacement was the largest among the three subgroups,and an in-out-in phenomenon appeared.The peak stress of the screws in the screw elevation group was the largest among the three subgroups,but the peak displacement was the smallest.(4)It is concluded that for sub-capitated femoral neck fractures that are completely anatomically reduced,it is recommended to use standard inverted triangular nails for fixation.When the hip varus and hip valgus occur within the allowable range of the reduction standard,it is recommended to use the inverted triangle screw to fix it by rotating the corresponding angle in the same direction as the hip varus or valgus.

OBJECTIVE To provide a detailed report and interpretation of the method and results for determining the weights of the technical indicators from the “multi-dimensional and multi-criteria comprehensive evaluation index system （first edition）” stated in Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine. METHODS Normalization calculations were performed on the comprehensive weight values calculated by the analytic hierarchy process and expert weighting method to obtain the objective weights of the indicators. RESULTS The weight results of the six primary dimensions in the current comprehensive evaluation indicator system of Chinese patent medicine showed effectiveness dimension＞ safety dimension＞standard dimension＞application dimension＞scientific dimension＞economic dimension， with weight values of 0.281 0， 0.268 5， 0.195 8， 0.107 3， 0.096 1 and 0.051 3 respectively， consistent with the results of most researches currently. CONCLUSIONS The process of weight determination in this indicator system is scientifically reasonable， with clear methods and clear interpretations， and is worthy of further optimization and widespread application.

Objectives To explore the feasibility of temporary veno-venous extracorporeal membrane oxygenation(VV-ECMO)technology for early on-site treatment,through establishing an animal model of severe blast lung injury in goats by free-field chemical explosion experiments in high-altitude regions.Methods A total of 16 adult goats were selected,and divided into the control group and the treatment group according to the random number table method,with 8 goats in each group.A model of severe blast lung injury was established at an altitude of 4 600 meters above sea level,then the goats in the control group were given respiratory support and the goats in the treatment group were given temporary VV-ECMO treatment.The survival status of the goats 15 minutes after injury was recorded,the vital signs[including body temperature,respiration rate,heart rate,and mean arterial pressure(MAP)]and arterial blood gas analysis indicators[including pH,arterial partial pressure of oxygen(PO2),arterial partial pressure of carbon dioxide(PCO2),oxygen saturation(SaO2),lactate(LAC),calcium(Ca2+),hematocrit(HCT),and hemoglobin(Hb)]before injury and 1 hour,2 hours,3 hours after injury were compared in the two groups.The post-mortem examination was performed on all dead goats and sacrificed goats after treatment,the severity of lung injury was assessed by organ injury scaling(OIS),and the lung injury score was evaluated by abbreviated injury scale(AIS).The wet-to-dry weight ratio(W/D)and lung coefficient were calculated.Results Within 15 minutes after the explosion,4 goats in the control group died and 4 goats survived;and 5 goats in the treatment group died and 3 goats survived.There was no statistically significant difference in the body temperature,respiration rate,heart rate,or MAP before and after injury between the two groups(P>0.05).The PaO2 and SaO2 1 hour,2 hours,and 3 hours after injury in the treatment group were superior than those in the control group(P<0.05),the Ca2+ 2 hours after injury was significantly higher than that in the control group(P<0.05),and there was no statistically significant difference in the pH,PCO2,LAC,HCT or Hb at different time points after injury between the two groups(P>0.05).There was no statistically significant difference in the OIS,AIS or lung coefficient between the two groups(P>0.05),but the W/D of the lung tissue in the control group was lower than that in the treatment group(P<0.05).Conclusion We have established a novel,feasible,and stable treatment effect temporary VV-ECMO animal treatment strategy for the first time in the high-altitude regions,which can provide animal experiment evidence for the early on-site VV-ECMO treatment of severe blast lung injury in high-altitude regions.

AIM To study the phenylpropanoids from Brandisia hancei Hook.f.and their antioxidant activities.METHODS The extract from B.hancei was isolated and purified by Rp-C18,MCI,semi-preparative HPLC,silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The cytotoxicities was determined by MTT method,and the antioxidant activities were determined by DPPH and ABTS+free radical scavenging methods.RESULTS Fifteen phenylpropanoids were isolated and identified as(+)-pinonesinol(1),(-)-medioresinol(2),(-)-syringaresinol(3),buddlenol D(4),(7R,7'R,7″S,8S,8'S,8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol(5),(-)-(7R,7'R,7″R,8S,8'S,8″S)-4',4″-dihydroxy-3,3',3″,5-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineolignan-7″,9″-diol(6),hedyotol A(7),dracunculifoside R(8),acteoside(9),isoacteoside(10),arenarioside(11),isomartynoside(12),curcasinlignan B(13),erythro-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-l-ol(14),citrusin C(15).Compounds 1-4 and 9-10 had no obvious cytotoxicity to HepG2 hepatoma cells.Compounds 1,3,9,10 and 12 had strong scavenging activities against DPPH radicals.Compounds 1-3,9-10,12 and 14 showed strong scavenging activities against ABTS+radical.CONCLUSION Compounds 1-8 and 12-15 are isolated from genus Brandisia for the first time.The phenylpropanoids from B.hancei show strong antioxidant activities.

OBJECTIVE: To investigate the efficacy of posterior three-columns osteotomy in the treatment of severe tuberculous angular kyphosis. METHODS: Total of 33 patients with severe tuberculous angular kyphosis were treated with posterior three-columns osteotomy from January 2006 to January 2019 including 24 males and 9 females with an average age of (40.6±23.3) years old ranging from 15 to 62 years old and an average disease duration of (23.5±15.5) years ranging from 4 to 40 years. The Cobb's angle of kyphosis was (118.65±28.82)°. Interradicular bone-disc-bone osteotomy(BDBO), posterior-only vertebral column resection (PVCR) and posterior multilevel vertebral osteotomy (PMVO) were performed to correct spinal deformity individually. The visual analogue scale (VAS), Oswestry disability index (ODI), sagittal vertical axis (SVA), ASIA spinal cord functional classification and motor function score, and deformity correction rate were measured and statistically analyzed before, after and at the final follow-up. RESULTS: Total of 33 patients were followed up from 15 to 96 months with an average of (38.00±6.38) months. The last follow-up of kyphosis Cobb angle (23.88±5.45)° showed no significant loss from postoperative 12 months (20.40±9.13)°, P>0.05. The SVA, VAS, ODI and ASIA spinal cord functional classification and motor function score were significantly improved at 1 year and last follow-up after operation(P<0.01). The fusion time of the osteotomy site was (18.50±5.16) months. The ASIA classification of 15 patients with spinal cord injury were improved by at least 2 grades after operation, and their daily life and work ability were various levels of restored. Postoperative complications of spinal cord injury occurred in 3 cases. CONCLUSION Posterior three-columns osteotomy is the most effective method for the treatment of angular kyphosis of spinal tuberculosis.Careful preoperative design and individualized osteotomy can not only correct the deformity, but also a successful decompression to the spinal cord and promote the recovery of spinal cord function.
Humans ; Male ; Female ; Osteotomy/methods* ; Kyphosis/surgery* ; Adult ; Adolescent ; Middle Aged ; Young Adult ; Tuberculosis, Spinal/complications* ; Treatment Outcome

OBJECTIVE: To investigate the treatment outcome of laparoscopic partial nephrectomy in the patients with renal tumors of moderate to high complexity (R.E.N.A.L. score 7-10). METHODS: In the study, 186 patients with a renal score of 7-10 renal tumors who underwent laparoscopic partial nephrectomy in Peking University Third Hospital from February 2016 to April 2021 were selected. Laparoscopic partial nephrectomy was performed after examination. The patients were followed-up, and their postoperative hemoglobin, creatinine, complications, and length of hospital stay recorded. The data were represented by mean±standard deviation or median (range). RESULTS: There were 128 males and 58 females in this group, aged (54.6±12.8) years, with body mass index of (25.4 ± 3.4) kg/m²; The tumors were located in 95 cases on the left and 91 cases on the right, with maximum diameter of (3.1±1.2) cm. The patient's preoperative hemoglobin was (142.9±15.8) g/L, and blood creatinine was 78 μmol/L (47-149 μmol/L). According to preoperative CT images, the R.E.N.A.L. score was 7 points for 43 cases, 8 points for 67 cases, 9 points for 53 cases, and 10 points for 23 cases. All the ope-rations were successfully completed, with 12 cases converted to open surgery. The operation time was 150 minutes (69-403 minutes), the warm ischemic time was 25 minutes (3-60 minutes), and the blood loss was 30 mL (5-1 500 mL). There were 9 cases of blood transfusions, with a transfusion volume of 800 mL (200-1 200 mL). Postoperative hemoglobin was (126.2±17.0) g/L. The preoperative crea-tinine was 78 μmol/L (47-149 μmol/L), the postoperative creatinine was 83.5 μmol/L (35-236 μmol/L), the hospital stay was 6 days (3-26 days), and surgical results achieved "the trifecta" in 87 cases (46.8%). In the study, 167 cases were followed up for 12 months (1-62 months), including 1 case with recurrence and metastasis, 4 cases with metastasis, and 2 cases with other tumors (1 case died). CONCLUSION Laparoscopic partial nephrectomy is safe and effective in the treatment of renal tumors with R.E.N.A.L. score of 7-10. Based on the complexity of the tumor, with the increase of difficulty, the warm ischemia time and operation time tend to increase gradually, while "the trifecta" rate gradually decreases. The complications of this operation are less, and the purpose of preserving renal function to the greatest extent is achieved.
Male ; Female ; Humans ; Creatinine ; Retrospective Studies ; Kidney Neoplasms/pathology* ; Nephrectomy/methods* ; Treatment Outcome ; Laparoscopy ; Hemoglobins