The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective:To explore the effect of scalp electroacupuncture (EA) on central pain sensitization in rats with knee osteoarthritis (KOA).Methods:Thirty-two 8-week-old female Sprague-Dawley rats were randomly divided into a blank control group, a model group, an electroacupuncture (EA) group and a sham EA group, each of 8. All of the rats except those in the control group had KOA induced through intra-articular monosodium iodoacetate injections in the right knee. Two weeks later the EA group rats began receiving daily head EA sessions 6 days/week for 2 weeks. The sham EA group received identical but non-therapeutic stimulation. The blank control and model groups received no EA intervention. Before the modelling and 3, 7, 14, 21 and 28 days later, all of the rats completed bipedal balance pain tests and mechanical allodynia evaluations. After the testing on day 28, all of the rats were euthanized for molecular analyses. Western blotting and immunohistochemistry were performed to examine protein expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), and cannabinoid receptor type 1 (CB1R) in both the periaqueductal gray (PAG) matter and spinal dorsal horns (SDHs). Serum levels of substance P (SP) and 5-hydroxytryptamine (5-HT) were also quantified using enzyme-linked immunosorbent assays.Results:Three days after successful modeling, the average weight-bearing capacity of the right hind limb in the model, sham EA and EA groups was significantly lower than that of the blank controls. It reached its lowest level on the 14th day after modeling. Concurrently, the pain responses in those three groups were significantly higher than among the controls, also peaking on the 14th day after modeling. After two weeks of electroacupuncture, the electroacupuncture group showed significant improvement in both right hind limb weight-bearing capacity and pain response compared to the model group. Meanwhile, the levels of BDNF and TrkB protein in the periaqueductal gray matter were significantly higher in the model group than among the blank controls, while the electroacupuncture group exhibited significantly reduced expression of BDNF and TrkB proteins compared to the model group, along with significantly increased CB1R protein expression. The model group showed significantly elevated expression of both BDNF and TrkB proteins in the spinal dorsal horn compared to the blank control group, while there were significant differences between the EA and model groups in the expression of BDNF, TrkB and CB1R proteins. Immunohistochemical analysis on day 28 revealed that the EA group had significantly fewer BDNF- and TrkB-positive cells in the PAG compared to the model group, with significantly more CB1R-positive cells. In the SDH, the model group exhibited significantly increased numbers of BDNF- and TrkB-positive cells compared to the blank control group, whereas significant differences were found between the EA and blank control groups in the numbers of BDNF-, TrkB- and CB1R-positive cells. Serum analysis on day 28 demonstrated that substance P and 5-hydroxytryptamine levels in the model, sham EA and EA groups were significantly higher than in the blank control group, on average. However, no significant differences were observed in serum SP and 5-HT levels between the EA and model groups.Conclusions:Scalp EA significantly alleviates central pain sensitization in KOA, at least in rats, potentially by suppressing BDNF and TrkB expression while upregulating CB1R expression in the PAG matter and the SDH.

Objective To observe the difference of bone micro-structure in different regions of proximal femur,micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers.Micro-CT scanning was used to measure the trabecular thickness(Tb.Th),trabecular number(Tb.N),trabecular space(Tb.Sp),connectivity(Conn)and bone mineral density(BMD)and other parameters in 7 regions of proximal femur,including proximal pressure trabecular(PPT),distal pressure trabecular(DPT),femoral head-neck junction(FHNJ),head and neck of femoral neck(HNFN),the base of femoral neck(BPFN),intertrochanteric line(IL)and greater trochanter(GT).Results The bone mineral density of IL and GT were higher than those of BPFN,FHNJ,DPT and PPT.The trabecular thickness of GT was the largest,followed by IL,BPFN and HNFN,and the smallest was FHNJ,DPT and PPT.The trabecular space of IL was larger than that of GT,and the data of both were larger than those of other parts,among which DPT and PPT were the smallest.The trabecular number of IL and GT were the smallest,BPFN,HNFN and FHNJ were larger,and DPT was the largest.The volume fraction of IL was the smallest,BPFN and HNFN were larger,DPT and PPT were the largest.Conclusion The bone density,trabecular thickness,bone volume,and total volume of GT and IL in the proximal femur of elderly patients are all relatively large,so the reason for the high incidence of fractures is not due to weak internal bone microstructure;The bone density,trabecular thickness,and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small.If it is necessary to perform core decompression for prosthesis filling at this location,the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.

The development of artificial intelligence(AI)technology has provided new avenues for the public to access health information.While both domestic and international research and practical applications of health conversational AI have emerged,there remains a lack of consensus on the key issues surrounding their development.Based on a comprehensive review of domestic and international literature and multiple rounds of expert consultations,the study focuses on six issues:the definition,characteristics,application scenarios,evaluation elements,evaluation methods,as well as prospects and challenges of AI-driven health consultation systems,and develops the practice guideline for health conversational artificial intelligence.The findings aim to provide scientific reference for promoting the innovative application of AI technology in the healthcare field.

Objective To investigate the clinical effects of different bone graft materials in internal fixation surgery for Schatzker type Ⅱ tibial plateau fracture(TPF).Methods A total of 108 patients with Schatzker type Ⅱ TPF in Lianyungang Municipal Oriental Hospital were selected and randomly assigned to the allogeneic cancellous bone and the artificial bone groups,with 54 cases in each group.The perioperative indicators,four coagulation items[thrombin time(TT),fibrinogen(FIB),activated partial thromboplastin time(APTT),prothrombin time(PT)],bone metabolic factors[bone gla protein(BGP),alkaline phosphatase(ALP),precollagen type Ⅰ N-terminal peptide(PINP)],knee motion,and numerical rating scale(NRS)score before and after operation,as well as complications,prognosis,bone graft stability were compared in the two groups.Results The hospital stay and fracture healing time in the artificial bone group were shorter than those in the allogeneic cancellous bone group(P<0.05).On the 7th day after surgery,the artificial bone group had longer peripheral blood APTT,TT and PT than the allogeneic cancellous bone group,and lower FIB level than the allogeneic cancellous bone group(P<0.05).The serum ALP,BGP and PINP levels 3 months after surgery in the two groups were higher than those before surgery(P<0.05).At 3 months after surgery,the ranges of knee extension and flexion in the artificial bone group were greater than those in the allogeneic cancellous bone group(P<0.05),and the NRS score was lower than that in the allogeneic cancellous bone group(P<0.05).The incidence of complications in the artificial bone group was lower than that in the allogeneic cancellous bone group(P<0.05).The excellent and good rate of knee joint function recovery 6 months after surgery in the artificial bone group was higher than that in the allogeneic cancellous bone group(P<0.05).The overall collapse height of the tibial lateral condylar articular surface,overall increase of lateral compartment angle,and overall loss height of lateral compartment 12 months after surgery in the artificial bone group were lower than those in the allogeneic cancellous bone group(P<0.05).Conclusion Compared with allogeneic cancellous bone,the use of artificial bone as the graft material during internal fixation in patients with Schatzker type Ⅱ TPF can more effectively ameliorate the postoperative coagulation status,reduce the incidence of complications,and enhance the graft stability,which is conducive to better prognosis.

The development of artificial intelligence(AI)technology has provided new avenues for the public to access health information.While both domestic and international research and practical applications of health conversational AI have emerged,there remains a lack of consensus on the key issues surrounding their development.Based on a comprehensive review of domestic and international literature and multiple rounds of expert consultations,the study focuses on six issues:the definition,characteristics,application scenarios,evaluation elements,evaluation methods,as well as prospects and challenges of AI-driven health consultation systems,and develops the practice guideline for health conversational artificial intelligence.The findings aim to provide scientific reference for promoting the innovative application of AI technology in the healthcare field.