Objective:To identify and analyze the genuine medicinal plant Gentiana scabra Bge. from 9 regions in Liaoning Province using DNA barcode technology based on the base sequence of internal transcribed spacer. Methods:DNA was extracted from the medicinal parts of 26 Gentiana scabra Bge. samples by using DNA kit extraction method. The ITS sequence was amplified through polymerase chain reaction (PCR), and then two-way sequencing was carried out. Other sources and outgroup sequences of the medicinal plant Gentiana scabra Bge. were downloaded from Genbank. After the sequencing results were spliced by using SeqMan 7.1.0 software, MEGA 7.0 software was used to analyze and compare the data, and calculate the genetic distance of K2P (Kimura 2-parameter). The phylogenetic tree was established by Neighbor-Joining (NJ) method for analysis. Results:According to the results of NJ cluster tree, all Gentiana scabra Bge. samples from different sources were clustered into one large branch, and Gentiana scabra Franch. and Gentiana triflora Pall. were clustered into one branch respectively, with obvious differences; Gentiana scabra and Gentiana manshurica Kitag. were clustered into one branch, and the genetic relationship was relatively close. In combination with the variation site and genetic distance, the base sequences of Gentiana scabra and Gentianamanshurica were very similar, and the interspecific differences were very small. Except for the intraspecific variation of only one sample collected in Liaoning Province, the base sequences of the other samples were the same, and there was no difference between " Gentiana scabra Bge. in Qingyuan" and Gentiana scabra Bge. samples from other regions in Liaoning Province. Conclusion:The DNA barcode technology of ITS sequence can be used to differentiate and identify medicinal plant Gentiana scabra Bge. and its original plants from different sources with a high success rate.

Objective:To use rbcL sequences to identify the rhizomes of the Liaoning collection of Atractylodes chinensis (DC.) Koidz.; To provide a basis for ensuring the feasibility of cultivation of the native herb in Liaoning Province. Methods:A total of 30 rhizomes of Atractylodes chinensis (DC.) Koidz. were collected from 10 regions cultivated in Liaoning Province, and the total DNA was extracted. DNA barcodes were screened by PCR, and the rbcL sequences of the samples were amplified and sequenced, and the amplification and sequencing success rates were calculated. Sequence alignment was performed using MEGA 7.0 software; a systematic clustering tree was constructed using the neighbour-joining method. Results:The success rates of DNA extraction from the rhizomes of Atractylodes chinensis (DC.) Koidz. were all 93.3%, and the success rates of PCR amplification and sequencing were all 100%. Among the 30 samples of Atractylodes chinensis (DC.) Koidz. in Liaoning Province, two samples had intraspecific variation, and the rest of the base sequences of Atractylodes chinensis (DC.) Koidz. were identical. Atractylodes chinensis (DC.) Koidz. was closer to the herbs of the genus Cangzhu, a relative species of Asteraceae, and was genetically more distant from the rest of Asteraceae. The NJ tree could distinguish Atractylodes chinensis (DC.) Koidz. and its relatives. Conclusion:The quality of Atractylodes chinensis (DC.) Koidz. cultivars in Liaoning Province is basically similar, and the rbcL sequence can be used as a valid sequence fragment for the identification of Atractylodes chinensis (DC.) Koidz. DNA barcode.

ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Tongue diagnosis is an important method of TCM diagnosis and treatment.Tongue is the key link of auxiliary diagnosis of tongue feature extraction and processing,and also is the bottleneck of intelligent tongue diagnosis in traditional Chinese medicine.Using image processing,artificial intelligence technology to the tongue as a quantitative and identify characteristics of traditional Chinese medicine,looking for both conforms to the original thinking of TCM,and TCM tongue diagnosis method of accurately,has become a common concern of traditional Chinese medicine and computer field.From the mobile terminal tongue as auxiliary diagnostic system of traditional Chinese medicine tongue acquisition basic attribute,tongue diagnosis and image information building,tongue like features are required for accurate extraction and so on related key technology is analyzed,and build overall architecture,so as to provide technical reference for the tongue like intelligent diagnosis,promote the development of technology of tongue diagnosis in traditional Chinese medicine modernization.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

As China's manned space missions gradually develop towards long-term residence and deep space exploration,astronauts will face increasingly severe psychological challenges.As a psychological adjustment method involving multiple disciplines such as music,psychology,and medicine,music therapy has the advantages of being convenient to implement,cost-effective,and highly personalized.This paper integrates the concept of music therapy and explores the research progress of music therapy in regulating psychological states in aspects such as physiology,emotional regulation,cognitive ability,and interpersonal relationships.Combined with the mechanism of action of music therapy and the practical situation in the field of manned spaceflight,it aims at the future development trends and problems to be solved,to construct a music therapy system for astronauts during on-orbit flight and ground daily training.This will help astronauts achieve healthy physical and mental development and promote the completion of missions.

Objective To construct lipid nanoparticles(lipopeptide-lipid nanoparticle,LP-LNP)with novel lipopeptides as adjuvants,and initially explore their synergistic effect on mRNA vaccines.Methods Two novel lipopeptides,SS-10 and SQ18,were designed and synthesized.Microfluidic technology was used to encapsulate lipopeptides in different proportions,as well as mRNAs encoding enhanced green fluorescent protein(eGFP),firefly luciferase(F-luc),and ovalbumin(OVA)into lipid nanoparticles to construct an mRNA delivery system with novel lipopeptides as adjuvants(LP-LNP).The particle size and polydispersity coefficient of LP-LNP were measured using dynamic light scattering.The activation effect on Toll-like receptors 2(TLR2)was detected using HEK-BlueTM mTLR2 reporter cells to screen the optimal lipopeptide ratio.The preferred LP-LNP-eGFP-mRNA was transfected into HEK293T cells,and the expression of eGFP was observed under a fluorescence microscope.In vivo imaging was used to investigate the expression level of LP-LNP-F-luc-mRNA in mice.Flow cytometry was used to evaluate the ability of LP-LNP-OVA-mRNA to induce the maturation of dendritic cells(DCs)in draining lymph nodes and cross-presentation of antigens after immunization.Results Lipopeptides SQ18 and SS-10 were incorporated into LNP at 0.50％and 0.75％molar ratios,respectively,to obtain LP-LNP with uniform particle size,high encapsulation efficiency,and good in vitro safety.The ability of this formulation to activate TLR2 was significantly stronger than the positive control Pam2CSK4(P＜0.01).The preferred LP-LNP obtained effective in vitro transfection,and LP-LNP prepared with SQ18 at 0.50％molar ratio had significantly better in vivo transfection efficiency than traditional LNP(P＜0.01),and significantly promoted the maturation of DCs in draining lymph nodes and cross-presentation of antigens(P＜0.05).Conclusion LP-LNP with novel lipopeptides as adjuvants can enhance the delivery capacity of mRNA and further improve the immune effect of mRNA vaccines.

Background and objective Invasive mucinous adenocarcinoma(IMA)was a rare and specific type of lung adenocarcinoma,which was often characterized by fewer lymphatic metastases.Therefore,it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis(TNM)staging.So,this study aimed to develop Nomo-grams to predict outcomes of patients with pathologic N0 in resected IMA.Methods According to the inclusion criteria and exclusion criteria,IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University(training cohort,n=78)and Ningbo No.2 Hospital(validation cohort,n=66)were reviewed between July 2012 and May 2017.The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established,and the performances of models were evaluated.Finally,the validation cohort data was put in for external validation.Results Univariate analysis showed that pneumonic type,larger tumor size,mixed mucinous/non-mucinous component,and higher overall stage were significant influence factors of 5-year progression-free survival(PFS)and overall survival(OS).Multivariate analysis further indicated that type of imaging,tumor size,mucinous component were the independent prognostic factors for poor 5-year PFS and OS.Moreover,the 5-year PFS and OS rates were 62.82％and 75.64％,respectively.In subgroups,the sur-vival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients,respectively.The C-index of Nomograms with 5-year PFS and OS were 0.815(95％CI:0.741-0.889)and 0.767(95％CI:0.669-0.865).The calibration curve and decision curve analysis(DCA)of both models showed good predictive performances in both cohorts.Conclusion The Nomograms based on clinicopathological characteristics in a certain extent,can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.