Analysis of the Treatment Strategy of Heart Failure with Preserved Ejection Fraction Based on ZHANG Boli's Theory of “Damp-turbidity and Phlegm-rheum Type of Diseases” / 中医杂志

Professor ZHANG Boli believed that the core pathogenesis of heart failure with preserved ejection fraction （HFpEF） is weak pulse at yang and wiry pulse at yin. By referring to the theory of “damp-turbidity and phlegm-rheum type of diseases”， he proposed that yin pathogens of damp-turbidity and phlegm-rheum may damage yang qi in each stage of HFpEF， thus aggravating the trend of weak pulse at yang and wiry pulse at yin， which played an important role in the deterioration of HFpEF. Therefore， Professor ZHANG Boli advocated that importance should be attached to the elimination of yin pathogen and the protection of yang qi during the various stages of HFpEF in order to delay the aggravation of weak pulse at yang and wiry pulse at yin； he put forward the idea of staged treatment that “yin pathogen should be dispelled and yang qi should be demonstrated”； and he formulated the treatment strategy of treating the disease as early as possible， eliminating pathogens and protecting yang， interrupting the disease trend， using warm-like medicinals， and activating blood circulation， to enrich the theoretical system of traditional Chinese medicine in the treatment of HFpEF.

Preliminary experience of gasless transoral vestibular robotic thyroidectomy / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P25, P75), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.

Research progress of exosome delivery vehicles in tumor phototherapy / 药学学报

Exosome is a self-secreted phospholipid bilayer nanovesicles, and has shown great potential in drug delivery field due to the important advantages of low immunogenicity and homologous targeting. Phototherapy, mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT), utilize light to activate photoactive drug for tumor cell killing. The advanced therapeutic strategy shows low toxic side-effect and non-invasion precise advantages, and thus has made great progress in tumor treatment over the past few years. Therefore, using exosomes as a drug delivery system to deliver phototherapeutic agents can improve therapeutic performances with a reduced side-effect, and further enhance their application potential for clinical tumor therapy. This review focus on the rising cross-subjects field involving exosomes and phototherapy, and mainly introduce the research progress and relative case of exosomes-based delivery system for cancer phototherapy. Additionally, the advantages and challenges of exosome-based phototherapy are also discussed and proposed.

Inheritance, innovation and development of traditional Chinese medicine in new era call for scientific supervision / 中国中药杂志

Pharmaceutical products need to ensure the effectiveness, safety and quality controllability through scientific supervision, and as the broad masses of the people are full of new expectations for the supply of high-quality traditional Chinese medicine products, the reform and innovation of traditional Chinese medicine regulatory policies are also facing new opportunities and new challenges. National Medical Products Administration, National Administration of Traditional Chinese Medicine and other relevant departments have implemented the requirements of the Party Central Committee and the State Council, vigorously promoted the reform of the regulatory system in line with the characteristics of traditional Chinese medicine, introduced a series of innovative policies, and achieved phased results. Including the new registration classification standards in line with the characteristics of traditional Chinese medicine, encouraging the development of classical formulas and hospital preparations, encouraging the research and development of symptomatic Chinese medicines, and gra-dually improving the "three-combined " evidence system. However, in the face of the development problems of traditional Chinese medicine in the new era, it is still necessary to improve the scientific supervision system, further optimize the management measures for the registration of traditional Chinese medicines based on classical formulas, accelerate the improvement of the standard system for traditional Chinese medicine formula granules, and form management measures to encourage and support the secondary development of traditional Chinese medicines. In terms of scientific supervision of traditional Chinese medicine, it is necessary to follow the characteristics and development laws of traditional Chinese medicine itself, comprehensively consider the characteristics of epochal, scientific and systematic in regulatory policies, and serve the inheritance and innovative development of traditional Chinese medicine with scientific supervision.

Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway / 中国中药杂志

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 μmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 μmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 μmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 μmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 μmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 μmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

Technical difficulties and countermeasures of digestive tract reconstruction in robotic radical gastrectomy for gastric cancer / 中华胃肠外科杂志

There still remain some problemsin digestive tract reconstruction after robotic radical gastrectomy for gastric cancer at present, such as great surgical difficulties and high technical requirements. Based on the surgical experience of the Gastric Surgery Department of Union Hospital, Fujian Medical University and the literatures at home and abroad, relevant issues are discussed in terms of robotic radical distal gastrectomy (Billroth I, Billroth II, and Roux-en-Y gastrojejunostomy), proximal gastrectomy (double-channel and double-muscle flap anastomosis), and total gastrectomy (Roux-en-Y anastomosis, functional end-to-end anastomosis, FEEA, π-anastomosis, Overlap anastomosis, and modified Overlap anastomosis with delayed amputation of jejunum, i.e. later-cut Overlap). This article mainly includes (1) The principles of digestive tract reconstruction after robotic radical gastrectomy for gastric cancer. (2) Digestive tract reconstruction after robotic radical distal gastrectomy: Aiming at the weakness of traditional triangular anastomosis, we introduce the improvement of the technical difficulty, namely "modified triangular anastomosis", and point out that because Billroth II anastomosis is a common anastomosis method in China at present, manual suture under robot is more convenient and safe, and can effectively avoid anastomotic stenosis. (3) Digestive tract reconstruction after robotic proximal gastrectomy: It mainly includes double channel anastomosis and double muscle flap anastomosis, but these reconstruction methods are relatively complicated, and robotic surgery has not been widely carried out at present. (4) Digestive tract reconstruction after robotic total gastrectomy: The most classic one is Roux-en-Y anastomosis, mainly using circular stapler for end-to-side esophagojejunal anastomosis and linear stapler for side-to-side esophagojejunal anastomosis, for which we discuss the solutions to the existing technical difficulties. With the continuous innovation of robotic surgical system and anastomosis instruments, and with the gradual improvement of anastomosis technology, it is believed that digestive tract reconstruction after robotic radical gastrectomy for gastric cancer will have a good application prospect in gastric cancer surgery.

Establishment of artificial neural network model for predicting lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer / 中华胃肠外科杂志

Objective: To establish a neural network model for predicting lymph node metastasis in patients with stage II-III gastric cancer. Methods: Case inclusion criteria: (1) gastric adenocarcinoma diagnosed by pathology as stage II-III (the 8th edition of AJCC staging); (2) no distant metastasis of liver, lung and abdominal cavity in preoperative chest film, abdominal ultrasound and upper abdominal CT; (3) undergoing R0 resection. Case exclusion criteria: (1) receiving preoperative neoadjuvant chemotherapy or radiotherapy; (2) incomplete clinical data; (3) gastric stump cancer.Clinicopathological data of 1231 patients with stage II-III gastric cancer who underwent radical surgery at the Fujian Medical University Union Hospital from January 2010 to August 2014 were retrospectively analyzed. A total of 1035 patients with lymph node metastasis were confirmed after operation, and 196 patients had no lymph node metastasis. According to the postoperative pathologic staging. 416 patients (33.8%) were stage Ⅱ and 815 patients (66.2%) were stage III. Patients were randomly divided into training group (861/1231, 69.9%) and validation group (370/1231, 30.1%) to establish an artificial neural network model (N+-ANN) for the prediction of lymph node metastasis. Firstly, the Logistic univariate analysis method was used to retrospectively analyze the case samples of the training group, screen the variables affecting lymph node metastasis, determine the variable items of the input point of the artificial neural network, and then the multi-layer perceptron (MLP) to train N+-ANN. The input layer of N+-ANN was composed of the variables screened by Logistic univariate analysis. Artificial intelligence analyzed the status of lymph node metastasis according to the input data and compared it with the real value. The accuracy of the model was evaluated by drawing the receiver operating characteristic (ROC) curve and obtaining the area under the curve (AUC). The ability of N+-ANN was evaluated by sensitivity, specificity, positive predictive values, negative predictive values, and AUC values. Results: There were no significant differences in baseline data between the training group and validation group (all P>0.05). Univariate analysis of the training group showed that preoperative platelet to lymphocyte ratio (PLR), preoperative systemic immune inflammation index (SII), tumor size, clinical N (cN) stage were closely related to postoperative lymph node metastasis. The N+-ANN was constructed based on the above variables as the input layer variables. In the training group, the accuracy of N+-ANN for predicting postoperative lymph node metastasis was 88.4% (761/861), the sensitivity was 98.9% (717/725), the specificity was 32.4% (44/136), the positive predictive value was 88.6% (717/809), the negative predictive value was 84.6% (44/52), and the AUC value was 0.748 (95%CI: 0.717-0.776). In the validation group, N+-ANN had a prediction accuracy of 88.4% (327/370) with a sensitivity of 99.7% (309/310), specificity of 30.0% (18/60), positive predictive value of 88.0% (309/351), negative predictive value of 94.7% (18/19), and an AUC of 0.717 (95%CI:0.668-0.763). According to the individualized lymph node metastasis probability output by N+-ANN, the cut-off values of 0-50%, >50%-75%, >75%-90% and >90%-100% were applied and patients were divided into N0 group, N1 group, N2 group and N3 group. The overall prediction accuracy of N+-ANN for pN staging in the training group and the validation group was 53.7% and 54.1% respectively, while the overall prediction accuracy of cN staging for pN staging in the training group and the validation group was 30.1% and 33.2% respectively, indicating that N+-ANN had a better prediction than cN stage. Conclusions: The N+-ANN constructed in this study can accurately predict postoperative lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer. The N+-ANN based on individualized lymph node metastasis probability has better accurate prediction for pN staging as compared to cN staging.

Effect of straight-line minimally invasive access cavity on the mechanical properties of maxillary first premolars: a finite element analysis / 中华口腔医学杂志

Objective: To investigate the effects of straight-line minimally invasive access cavity on the mechanical properties of endodontically treated maxillary first premolars using finite element analysis. Methods: Micro-CT data of twenty maxillary first premolars were collected for three-dimensional reconstruction. Three access cavities, including the conventional access cavity (ConvAC), the truss access cavity (TrussAC) and the straight-line minimally invasive access cavity (SMIAC), as well as the root canal treatment procedure, were simulated in all the 20 reconstruction samples of three-dimensional models, respectively. The peak von Mises stress on the cervical area of each model, as well as the stress distribution under vertical and oblique loading circumstances, were subsequently determined by using finite element analysis. Results: In comparison to the stresses of ConvAC [buccal cervical (BC): (188.7±13.4) MPa, palatal cervical (PC): (200.9±25.7) MPa], the stresses of TrussAC [BC: (146.0±12.9) MPa, PC: (167.6±15.9) MPa] (t=9.01, P<0.001; t=4.59, P<0.001) and SMIAC [BC: (142.6±13.7) MPa, PC: (168.1±17.4) MPa] (t=9.64, P<0.001; t=3.76, P=0.004) significantly reduced the peak von Mises stress on the cervical area of the maxillary first premolars after root canal treatment. Under vertical loading conditions, SMIAC also reduced the central tendency of stresses on the occlusal surface, cervical area and root. In the case of oblique loading conditions, similar results were observed. Under both loading conditions, there was no significant difference in the peak von Mises stress on the cervical area of the maxillary first premolar between TrussAC and SMIAC groups. Conclusions: The design of SMIAC could preserve the mechanical properties of the maxillary first premolar following root canal treatment, which might have certain clinical feasibility.

Effect analysis of trajectory screw technique in fragility fracture of pelvic ring / 中国骨伤

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.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Establishment of a platelet production model by bone marrow cavity transplantation of mouse primary megakaryocytes / 中华血液学杂志

Objective: To establish an intramedullary transplantation model of primary megakaryocytes to evaluate the platelet-producing capacity of megakaryocytes and explore the underlying regulatory mechanisms. Methods: Donor megakaryocytes from GFP-transgenic mice bone marrow were enriched by magnetic beads. The platelet-producing model was established by intramedullary injection to recipient mice that underwent half-lethal dose irradiation 1 week in advance. Donor-derived megakaryocytes and platelets were detected by immunofluorescence staining and flow cytometry. Results: The proportion of megakaryocytes in the enriched sample for transplantation was 40 to 50 times higher than that in conventional bone marrow. After intramedullary transplantation, donor-derived megakaryocytes successfully implanted in the medullary cavity of the recipient and produce platelets, which showed similar expression of surface markers and morphology to recipient-derived platelets. Conclusion: We successfully established an in vivo platelet-producing model of primary megakaryocytes using magnetic-bead enrichment and intramedullary injection, which objectively reflects the platelet-producing capacity of megakaryocytes in the bone marrow.

Study on postprandial bioequivalence of Diacerein capsules in healthy volunteers / 中国药房

OBJECTIVE To evaluate the postprandial bioequivalence of two kinds of Diacerein capsules in healthy volunteers with oral administration . METHODS A total of 24 adult healthy subjects were included and randomly divided into two groups ， with 12 subjects in each group . A randomized ，open，double-cycle cross -over trial design was adopted . Both groups took 50 mg of the test preparation （domestic Diacerein capsules ）or the reference preparation （Ambridine®）respectively at 30 min after eating the standard meal in the morning of the first day of each cycle of the trial . The cleaning period was one week . Blood samples were collected at different time points before and after taking the medicine and the protein was precipitated with methanol for sample pretreatment. The concentration of active metabolite rhein was determined by LC -MS/MS using emodin as internal standard . The pharmacokinetic parameters were calculated with DAS 3.2.9 software，and the bioequivalence of test and reference preparation were evaluated. RESULTS After the subjects took the test preparation and the reference preparation after meal ， the main pharmacokinetic parameters of rhein were as follows ：cmax were（3 517±1 121）and（3 225±755）ng/mL；AUC0－24h were （25 764±6 134）and（24 316±5 856）ng·h/mL；AUC0－∞ were（26 679±6 409）and（25 170±6 415）ng·h/mL；tmaxwere 3.50 （0.67，12.00）and 4.00（1.50，7.00）h；t1/2 were（4.26±1.12）and（4.19±1.05）h，respectively. The 90% confidence intervals of the geometric mean ratios of cmax，AUC0－24h and AUC 0－∞ were 100.8%-113.9%，103.1%-109.4% and 103.2%-109.9%，respectively. CONCLUSIONS The test preparation and reference preparation are bioequivalent in the postprandial state of healthy subjects .

Mechanism of Cancer Drug Resistance and Reversal Effect of Chinese Medicine： A Review / 中国实验方剂学杂志

Malignant tumor is a serious threat to human life and health. The prevalence and mortality of malignancies in China are increasing year by year. Conquering cancer has become a difficult problem for human beings. Chemical drug therapy combined with molecular targeted therapy is a general and preferred anti-tumor clinical scheme， but the side effects and the drug resistance of cancer cells often hinder the efficacy. Therefore， it is of great significance to study the mechanism of drug resistance and the methods to reverse drug resistance. Chinese medicine has the characteristics of complex components， multiple targets， low toxicity， etc. A large number of experimental studies have demonstrated that the effective components or extracts of Chinese medicine can inhibit the proliferation， migration， and invasion of cancer cells， and induce apoptosis， autophagy， differentiation， and senescence. In clinical practice， Chinese medicine has been applied to the protection against ttumor， adjuvant treatment， and later consolidation. The research on Chinese medicine is expected to promote drug resistance reversal and cancer therapy. Studies have shown that the combination of Chinese medicine and chemotherapy can reverse drug resistance and increase efficacy， which has become the mainstream trend of cancer treatment. This study reviewed the mechanisms of the drug resistance of cancer cells induced by self-protective autophagy， gene mutation， high expression of enzymes， abnormal signaling pathways， and abnormal expression of RNA and protein， and summarized how compounds isolated from Chinese medicine， single drug and its extract， and classic anti-cancer prescription reversed the drug resistance to lay a solid foundation for the further investigation of the anti-tumor effect of Chinese medicine.

Anti-tumor Effect of Draconis Sanguis Petroleum Ether Fraction on Human Gastric Cancer HGC-27 and MGC-803 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Draconis Sanguis petroleum ether fraction （DSPEF） on the proliferation， apoptosis， migration， and autophagy of human gastric cancer HGC-27 and MGC-803 cells， and preliminarily elucidate its molecular mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of DSPEF at different concentrations （0， 20， 40， 60， 80 mg·L-1） on the proliferation of HGC-27 and MGC-803 cells after 24， 48， 72 h. Hoechst staining and flow cytometry were used to explore the effects of DSPEF at different concentrations on the apoptosis and apoptosis rate of HGC-27 and MGC-803 cells after 48 h treatment， respectively. The wound healing assay and acridine orange staining were used to investigate the effects of DSPEF on the migration and autophagy of HGC-27 and MGC-803 cells， respectively. Western blot was used to detect the expression levels of signaling pathway-related proteins in HGC-27 and MGC-803 cells treated with DSPEF for 48 h. ResultCompared with the control group， DSPEF（30 mg·L-1） inhibited the proliferation and migration of HGC-27 and MGC-803 cells in a concentration- and time-dependent manner （P<0.05）， and induced the apoptosis （P<0.01） and autophagy of HGC-27 and MGC-803 cells. DSPEF （60 mg·L-1） down-regulated the protein levels of phosphorylated mammalian target of rapamycin （p-mTOR） （P<0.05， P<0.01） and down-regulated phospho-signal transducer and activator of transcription 3 （p-STAT3） in HGC-27 and MGC-803 cells （P<0.01）， suggesting that DSPEF presumedly inhibited the proliferation and migration of human gastric cancer HGC-27 and MGC-803 cells and induced their apoptosis and autophagy by inhibiting the mTOR/STAT3 signaling pathway. ConclusionThe down-regulation of the mTOR/STAT3 signaling pathway may be involved in the anti-gastric cancer effect of DSPEF. This study is expected to provide a reference for the investigation of the anti-tumor effect of Draconis Sanguis.

Effect of Aqueous Extract of Trametes robiniophila on Proliferation of Human Prostate Cancer VCaP Cells / 中国实验方剂学杂志

ObjectiveTo investigate effect of aqueous extract of Trametes robiniophila （TRM，Huaier） on autophagy of human prostate cancer VCaP cells and Lamin B1 expression， so as to uncover its role in the proliferation of VCaP cells. MethodThe inhibitory effect of 0， 2， 4， 6， 8， 10 g·L-1 TRM aqueous extract on the proliferation of human prostate cancer VCaP cells at different time points were determined by cell counting kit-8 （CCK-8） assay. Acridine orange staining was conducted for analyzing the effect of TRM aqueous extract on the formation of autolysosomes in VCaP cells. After medication， the expression of microtubule-associated protein Ⅰ light chain 3 （LC3）， autophagy-related protein 3 （Atg3）， autophagy-related protein 5 （Atg5）， and autophagy-related protein 7 （Atg7） in VCaP cells were detected by Western blot. The effect of TRM aqueous extract alone and its combination with autophagy inhibitor bafilomycin A1 on the proliferation of VCaP cells were assayed by CCK-8 assay. RNA interference technology was used to explore the role of Lamin B1 in anti-proliferation of VCaP cells by TRM. ResultCompared with the blank group， TRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells in a time- and concentration-dependent manner （P<0.01）. Acridine orange staining showed that TRM aqueous extract promoted the formation of autolysosomes in VCaP cells. As revealed by Western blotting， TRM aqueous extract up-regulated the expression levels of LC3-Ⅱ， Atg3， Atg5， and Atg7 in contrast to those in the blank group （P<0.05）. All these indicated that TRM aqueous extract induced the autophagy of VCaP cells. In addition， autophagy inhibition impaired the sensitivity of VCaP cells to TRM aqueous extract （P<0.05）. The comparison with the blank group showed that TRM aqueous extract inhibited Lamin B1 protein expression in VCaP cells （P<0.01）， which in turns weakened the sensitivity of VCaP cells to TRM aqueous extract. ConclusionTRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells possibly by inducing autography and down-regulating Lamin B1 expression. This study has provided a theoretical basis for the clinical application of TRM.

Mechanism of Proteoglycan TPG-1 from Trametes robiniophila Inhibiting Growth of Human Hepatoma SK-HEP-1 Cells / 中国实验方剂学杂志

ObjectiveProteoglycan TPG-1 isolated from Trametes robiniophila（Huaier） has proved to have anti-hepatoma activity， and this paper aims to explore the molecular mechanism. MethodHuman hepatoma SK-HEP-1 cells were treated with TPG-1 （0， 0.05， 0.1， 0.25， 0.5， 1 g·L-1）. Then cell survival was detected by methyl thiazolyl tetrazolium （MTT） and apoptosis by flow cytometry. In addition， expression of genes in SK-HEP-1 cells treated with or without TPG-1 was examined by DNA microarray to preliminarily explore the anti-hepatoma molecular mechanism of TPG-1. ResultTPG-1 inhibited the proliferation of SK-HEP-1 cells as compared with the blank group （P<0.01）. After treatment with 1 g·L-1 TPG-1 for 48 h， the apoptosis rate of SK-HEP-1 cells increased （P<0.01）， and TPG-1 promoted the cleavage of cysteinyl aspartate specific proteinase （Caspase）-3 and Caspase-7， the key mediators of apoptosis （P<0.01）. Additionally， TPG-1 （1 g·L-1） suppressed the migration of SK-HEP-1 cells （P<0.05）. A total of 971 differentially expressed genes （DEGs） were identified in SK-HEP-1 cells after treatment with TPG-1， with 486 up-regulated and 485 down-regulated. These DEGs were mainly involved in the Gene Ontology （GO） terms of interleukin-6 （IL-6） biosynthesis， antigen processing and presentation， superoxide dismutase activity， positive regulation of mitogen-activated protein kinase kinase kinase （MAPKKK） cascade， nature killer （NK） cell chemotaxis， and chemokine biosynthesis， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways of nucleotide-binding oligomerization domain （NOD）-like receptor signaling pathway， apoptosis， Toll-like receptor signaling pathway， retinoic acid-inducible gene-Ⅰ （RIG-Ⅰ）-like receptor signaling pathway， T-cell receptor signaling pathway， and chemokine signaling pathway. Western blot results showed that TPG-1 （1 g·L-1） activated mitogen-activated protein kinase （MAPK） signaling pathway in SK-HEP-1 cells （P<0.01）. ConclusionProteoglycan TPG-1 inhibited the proliferation and migration， and induced apoptosis of human hepatoma SK-HEP-1 cells. Up-regulation of MAPK signaling pathway may be responsible for the growth inhibition of human hepatoma SK-HEP-1 cells by TPG-1.

Transoral robotic nasopharyngectomy for local recurrent nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the safety, efficacy, locally control and survival results of transoral Da Vinci robotic surgery for salvage treatment of locally recurrent nasopharyngeal carcinoma. Methods: This retrospective study included 33 patients with locally recurrent nasopharyngeal carcinoma (stage rT1-2, partial rT3) underwent transoral Da Vinci robotic surgery between October 2017 and January 2020. There were 20 males and 11 females, with an average age of (47.9±10.5) years. The lesions were localized in nasopharyngeal cavity in 14 cases, with extending to parapharyngeal space in 6 cases and the floor of sphenoid sinus in 13 cases. Transnasal endoscopy was used to assist surgery if necessary. SPSS 25.0 statistical software was used for statistical analysis. Results: Transoral robotic nasopharyngectomy was successfully performed in all cases without conversion to open surgery, of which 13 cases were combined with transnasal endoscopic surgery. The average operation time was (126.2±30.0) min, ranging from 90 to 180 min. The postoperative pathological margin was R0 (31 cases) and R1 (2 cases), with no tumor residue. Complications of surgery mainly included symptoms of headache, nasal dryness and velopharyngeal insufficiency without nasopharyngeal hemorrhage. Follow-up time was from 3 to 54 months. One case had tumor recurrence 11 months after operation, 1 case had ipsilateral cervical lymph node metastasis 27 months after operation, 2 cases had distant metastasis and 1 case died of nasopharyngeal hemorrhage 3 months after operation. The 1-year, 2-year and 3-year overall survival rates were 97.0%, 96.0% and 92.9%, respectively and the local recurrence free rates were 97.0%, 95.7% and 91.7%, respectively. Conclusion: Transoral robotic nasopharyngectomy is safe and feasible for local recurrent nasopharyngeal carcinoma in selected patients, with higher local control rate and quality of life.

Analysis of laboratory parameters and death risk in patients with thrombotic thrombocytopenic purpura / 中华检验医学杂志

Objective:To analyze the laboratory parameters and clinical characteristics of TTP patients, so as to provide reference for the timely diagnosis and death risk assessment or TTP.Methods:83 patients with TTP from June 2016 to March 2022 in our hospital were analyzed retrospectively. They were divided into survival and death groups. The differences in general information, clinical symptoms and laboratory parameters were compared between the two groups. The prognostic prediction score was constructed by combining parameters which differ between the two groups to calculate the corresponding mortality risk.Results:83 patients were included in the study, of whom 81.1% (60/74), 91.1% (72/79) and 86.2% (50/58) had increased AST, IBIL and cTnI results, and all (78/78) had higher LDH at admission. Hb was decreased in 97.5% (79/81) patients, and PLT of 97.5% (79/81) patients was less than 30×10 9/L. There were no significant differences in gender, age, blood type, presence of fever, ADAMTS-13 activity and PLASMIC score between the survival group (58 cases) and the death group (25 cases), but the proportion of neurologic symptoms in the death group was significantly higher than that in the survival group. AST, IBIL, cTnI and APTT at admission were significantly higher in the death group than in the survival group ( P<0.05). The risk of death was 4.86, 9.74, 3.71, and 5.33 for those with high AST, IBIL, APTT, and cTnI levels, respectively, compared with those with low levels at admission. At last, AST, IBIL, APTT, cTnI and neurological symptoms were included to construct a score model. For each 1 point increase, the risk of short-term death in TTP patients was 3.24. Conclusions:Multiple laboratory markers have high negative exclusion value for TTP. For TTP patients with high AST, IBIL, cTnI and APTT and neurologic symptoms, more attention and active treatment should be paid to reduce mortality.

The Comparison of Iron Deficiency Anemia Rat Treated with Hydroxypropyl Chitosan Ferrous Ion Complex and Ferrous Sulfate / 中国实验血液学杂志

OBJECTIVE@#To observe and compare the therapeutic effects of hydroxypropyl chitosan ferrous ion complex solution and ferrous sulfate solution in iron deficiency anemia rats and their effects on gastric mucosa.@*METHODS@#Seven rats were randomly selected from thirty five SPF grade SD rats as control group, and were fed with normal diet, distilled water (E). The rest of SD rats were fed with low iron feed and distilled water plus continuous tail vein bloodletting to establish the iron deficiency anemia model. After the model was established successfully, the rats were randomly divided into four groups: blank control group (A), iron deficiency anemia control group (B), ferrous sulfate group (C), hydroxypropyl chitosan ferrous ion complex (HPCTS-Fe@*RESULTS@#After modeling, except the normal control group, the hair color of the rats in the four groups showed dark yellow and the belly of the toes became white gradually. HGB, HCT, Ret%, MCV, MCH, MCHC and SF decreased significantly (P < 0.05). After treatment, the rats with dark yellow hair in group C and D were improved, and the toe abdomen turned pink gradually. RBC, HGB, HCT, Ret%, MCV, MCH, MCHC and SF in rats in group C and D increased, which were higher than those in group B (P < 0.05). The HGB of the rats in group D was higher than that of group C in day 28th during treatment and the Ret% was higher than that in group C at day 10th (P<0.05).After treatment, the liver and spleen of the rats in group C and D were lighter than those in group B (P<0.05).The gastric mucosa in group A, B, D and E was not damaged obviously, while it was slightly irritated and damaged in group C.@*CONCLUSION@#Hydroxypropyl chitosan ferrous complex solution can improve the hemoglobin level of SD rats with iron deficiency anemia, which is stronger than ferrous sulfate solution and shows no damage to gastric mucosa.