The present study identified chemical constituents of Honghua Xiaoyao Tablet (HXT) and explored its biological connotation and characteristics on the premenstrual syndrome (PMS) treatment from the "disease-syndrome-symptom" association network. UHPLC-Q Exactive Orbitrap HRMS technology was applied to analyze the chemical constituents in HXT. According to the composition principles, the compatible herbs of HXT were divided into the Shugan Jieyu group, Huoxue Tiaojing group and Yiqi Jianpi group. The candidate targets of the corresponding prescriptions of HXT efficacy groups were collected from the Pharmmapper database and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0. The gene set related to the clinical symptoms included in Traditional Chinese and Western Medicine diagnosis and treatment standards were obtained from SoFDA, GeneCards, DisGeNET, MalaCards and literature published. The "HXT candidate targets-PMS (liver depression, Qi stagnation, and blood stasis syndrome) genes" network was constructed based on the gene interaction information, and further, the core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes (KEGG) for exploring the therapeutic advantages in PMS treatment of HXT efficacy groups, which were further verified experimentally in vitro. A total of 109 components from HXT were identified, including 20 components from Shugan Jieyu group enriched in the neurological system, estrogen regulation, and "immune-inflammation" related pathways, 77 components from Huoxue Tiaojing group enriched in the blood-circulation system, "immune-inflammation" and estrogen regulation related pathways and 30 components from Yiqi Jianpi group regulating immune inflammation, digestive system, and hormone levels. The biochemical indicator detection demonstrated that both the levels of 5-HT and DA in the hypothalamus tissues and the levels of E₂, NO, VEGF and RLN in the uterine tissues of PMS model rats were lower than those in controls, which the levels of OT, PROG, IL-6, IL-1β and TNF-α in the uterine tissues were increased in PMS group, which were all reversed by the administration of HXT, indicating that this prescription may regulate the synthesis and secretion of estrogen, intervene in neurotransmitter synthesis and signal transduction, reverse the imbalance of "immune-inflammation", and regulate digestive system function through various biological pathways, exerting the liver-smoothing, Qi-regulating, blood-activating and spleen-tonifying comprehensive effects, leading to alleviating the "neuroendocrine-endocrine-immune" system and blood-circulation disorders. The relevant results may provide a reference for clarifying the advantages and efficacy of HXT in treating PMS with liver stagnation, Qi stagnation, and blood stasis syndrome, and exploring its therapeutic advantages. The animal experiment of this study was approved by the Ethics Committee of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (approval number: 2023B248).

Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

Autophagy, an evolutionarily conserved process by which components of the cell are degraded in lysosomes, may facilitate survival of cancer cells under stress conditions. 8-Azaguanine (8-AG), an inhibitor of purine nucleotide biosynthesis, shows antineoplastic activity in multiple tumor cells. However, chemoresistance has restricted its development as an anticancer agent, and the mechanism of 8-AG resistance is not fully understood. We report here that 8-AG induces a protective autophagy to eliminate its cytotoxicity, and inhibition of autophagy increases cellular sensitivity of cancer cells to 8-AG treatment. Using HepG2 or SMMC-7721 hepatic cancer cell lines, we found that 8-AG inhibited cell viability and induced intrinsic apoptosis, accompanied by the up-regulation of the pro-apoptotic protein BimS, one of Bim (also known as BCL-2-like protein 11, BCL2L11) isoforms. Furthermore, 8-AG treatment enhanced the autophagy flux by promoting the dephosphorylation and activation of Unc-51-like autophagy activating kinase 1 (ULK1) via Akt/mTORC1 (mammalian target of rapamycin complex 1) signaling inhibition. Depletion of autophagy-related gene 7 (ATG7) markedly enhanced the level of BimS, and promoted cell death in response to 8-AG. 8-AG in combination with autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (Baf A1) promoted the 8-AG-induced apoptosis in hepatic cancer cells. Altogether, these findings suggest that autophagy promotes chemoresistance of cancer cells for 8-AG, and blocking autophagy increases cellular sensitivity of cancer cells to 8-AG treatment.

OBJECTIVE: To investigate the clinical effect of a modified arthroscopic outside-in suture technique in the treatment of meniscus tear using a spinal needle. METHODS: From January 2015 to October 2017, 95 patients treated with this method were followed-up. Among these cases, there were 36 males and 59 females. The age of the patients ranged from 16 to 77 years, (46.79±18.07) years in average. Among them, there were 28 patieats aged 16-35, 53 patients aged 36-65, and 14 patients aged over 65 years old. 28 cases were diagnosed with medial meniscus tear, 43 cases with lateral meniscus tear and 24 cases with both medial and lateral meniscus tear. Causes of the injury included sports, sprain, etc. According to Barrett standard, the clinical healing of meniscus tear was judged. Lysholm score, knee range of motion, visual simulation score (VAS) and magnetic resonance imaging (MRI) were used to evaluate the postoperative knee function and recovery of the patients. RESULTS: The 95 patients were followed up for 22 to 36 months, with an average of (28.32±3.98) months. According to Barrett standard, 90 patients (94.7%) obtained meniscus clinical healing. Meniscal healing rates were 96.43%, 96.23% and 85.71% in the three age groups, respectively. The meniscal healing rate was lower in the elderly group, but there was no significant difference in statistical results (P=0.262). Five patients had deep tenderness in the joint space of the injured side, and the overstretch test was positive. The preoperative and postoperative VAS scores, Lysholm scores and knee motion were compared in each group, and the differences were statistically significant (P < 0.01). At the end of the last follow-up, there were no cases of knee joint effusion, swelling and interlocking, and the joint function was effectively improved in most patients. No surgical site infection, periarticular vascular/nerve injury or knotting reaction was found during the follow-up. CONCLUSION This modified arthroscopic outside-in suture technique using a spinal needle has the characteristics of simple operation, small trauma and rapid recovery, and the mid-term follow-up results were satisfactory. Therefore, we consider this method to be a safe and efficient method for the treatment of meniscus anterior horn and body tear.
Aged ; Arthroscopy ; Female ; Follow-Up Studies ; Humans ; Knee Injuries/surgery* ; Male ; Punctures ; Suture Techniques ; Tibial Meniscus Injuries/surgery*

OBJECTIVE: To evaluate the surgical technique and clinical effect of less invasive intrame-dullary nail fixation combined with titanium cable cerclage in the treatment of subtrochanteric fractures. METHODS: A retrospective study was performed in 46 cases of subtrochanteric fractures in Peking University People's Hospital from January 2015 to December 2017. Among them, there were 14 males and 32 females, with an average age of (77.83±10.66) years (44-92 years); 17 cases on the left side and 29 cases on the right side. The causes of injury included crash from a height, traffic accident and accidental fall. According to Seinsheimer classification, there were 26 cases of type Ⅱ, 11 cases of type Ⅲ, 9 cases of type Ⅳ, and these cases were all closed injury. After admission, these patients underwent continuous tibial tuberosity bone traction to maintain the length and force line of the lower extremity, so as to reduce the difficulty of intraoperative fracture reduction. Anticoagulant therapy was given before operation to reduce perioperative thrombotic complications. All the patients were treated with less invasive intramedullary nail fixation combined with titanium cable cerclage. Operation time, blood loss during surgery, time of fracture healing were recorded, Harris and Sanders scoring system were used to assess hip function after operation at each follow-up time point. RESULTS: All the included patients underwent surgery successfully. Average operative time and intraoperative blood loss of these patients were (131.09 ± 20.06) min and (191.96±111.03) mL, respectively. All the patients were followed up satisfactorily, with an average follow-up time of 28 months. The fractures received bone healing within 3-6 months, average hospital stay was (10.61±2.85) days. The Sanders score was excellent in 3 cases, good in 37 cases and common in 6 cases, with an excellent and good rate of 86.96%. The Harris score was excellent in 6 cases, good in 36 cases, with an excellent and good rate of 91.30%. There were no cases of wound infection, loss of reduction, nonunion of fracture or internal fixation failure. Hip pain symptoms were effectively relieved in most patients. CONCLUSION Less invasive intramedullary nail fixation combined with titanium cable cerclage can obtain good alignment and stability of fracture ends, which is an effective method for the treatment of subtrochanteric fractures.
Aged ; Aged, 80 and over ; Bone Nails ; Female ; Fracture Fixation, Intramedullary ; Fracture Healing ; Hip Fractures/surgery* ; Humans ; Male ; Retrospective Studies ; Titanium ; Treatment Outcome

Objective:To investigate the effects of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain function of APP/PS1 mice. Methods:Sixteen 4-month-old APP/PS1 mice in the same litter were randomly divided into model group (n = 8) and electroacupuncture group (n = 8). Eight transgenic negative mice in the same litter were as control group. The electroacupuncture group accepted electroacupuncture at Baihui and Shenting for 16 weeks. They were assessed with Object Recognition Test before and after intervention, and observed under small animal functional magnetic resonance imaging with regional homogeneity (ReHo) analysis. Results:Compared with the control group, the discrimination ratio decreased in the model group after intervention (P < 0.05), while it increased in the electroacupuncture group compared with that in the model group (P < 0.05). Compared with the control group, ReHo of right basal forebrain and left hippocampus decreased in the model group before intervention. Compared with the control group, ReHo decreased in bilateral hippocampus group and increased in retrosplenial cortex in the model group after intervention; while it increased in bilateral hippocampus and motor cortex and decreased in anterior cingulate gyrus in the electroacupuncture group compared with that in the model group. Conclusion:Electroacupuncture at Baihui and Shenting may delay the decline of learning and memory ability in Alzheimer's disease model mice, which may relate to the regulation of functional activities in hippocampus.

Objective:To investigate whether electroacupuncture (EA) at Quchi (LI11) and Zusanli (ST36) acupoints may regulate microRNA-34a (miR-34a) to promote neural stem cells differentiation in ischemic peripheral areas in rats with cerebral ischemia-reperfusion injury or not. Methods:A total of 108 rats were randomly assigned into sham group, model group and EA group, and each group was divided into three subgroups (three days, seven days and 14 days), with twelve rats in each subgroup. Besides, 16 rats were randomly divided into EA+dimethyl sulfoxide (DMSO) group and EA+miR-34a inhibitor group, with eight rats in each group. The middle cerebral artery occlusion (MCAO) model was induced for focal cerebral ischemia in rats. EA group was electroacupunctured at the ipsilateral Quchi and Zusanli acupoints on the second day. The dilatational wave was 1/20 Hz, 30 minutes every time, once a day for seven days, totally. At the same time, 5-Bromo-2′-Deoxyuridine (BrdU) was intraperitoneally injected twice a day, with an 8-hours interval. The DMSO and miR-34a inhibitor were injected into the lateral ventricle before modeling. The co-location condition was evaluated by immunofluorescence. The expression of miR-34a in ischemic peripheral areas was detected by reverse transcription real-time quantitative polymerase chain reaction. Results:The Longa's score was lower in EA group than in the model group (t > 2.084, P < 0.05). At the same time points, the paw print areas (right forepaw, right hind paw) and maximum pressures (right forepaw, right hind paw) of the affected limbs decreased in the model group than in the sham group (P < 0.05), and the paw print area of right hind paw gradually increased in the model group (P < 0.05); the paw print areas (right forepaw and right hind paw) of the affected limbs improved in EA group, compared with the model group (P < 0.05); and there was no significant difference in the maximum pressure of the affected limbs three days and seven days after electroacupuncture (P > 0.05); however, it was higher in EA group than in the model group 14 days after electroacupuncture (P < 0.05). And the paw print area of the right hind paw and the maximum pressure of the right forepaw gradually increased in EA group three days and seven days after electroacupuncture, which was in time-dependent manner (P < 0.05). The Nestin⁺/GFAP⁺ and BrdU⁺/GFAP⁺ cells expressed in ischemic peripheral areas both in the model group and EA group. And the Nestin⁺/GFAP⁺ and BrdU⁺/GFAP⁺ double positive cells increased in EA group compared to the model group three days, seven days and 14 days after electroacupuncture (t > 3.292, P < 0.05), and they reached peak seven days after electroacupuncture. The expression of miR-34a in ischemic peripheral areas was higher in the model group than in the sham group seven days after modeling (P < 0.01), however, the expression of miR-34a further increased in EA+DMSO group after electroacupuncture (P < 0.05). After injection of miR-34a inhibitor, the expression of miR-34a and BrdU⁺/GFAP⁺ cells was lower in EA+miR-34a inhibitor group than in EA group (P < 0.05). Conclusion:Electroacupuncture at Quchi and Zusanli acupoints could promote the neural stem cells differentiation in ischemic peripheral areas by regulation of miR-34a expression.

BACKGROUND: An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. METHODS: Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. RESULTS: Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. CONCLUSION: Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists. TRIAL REGISTRATION www.chictr.org.cn (No. ChiCTR-DDD-17013842).
Adult ; Aged ; Aged, 80 and over ; Artificial Intelligence ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neural Networks (Computer) ; Pathologists ; Radiologists ; Rectal Neoplasms ; diagnostic imaging ; mortality ; pathology