Objective To investigate the combined effect of berberine （BBR） and fluconazole （FLC） on FLC-tolerant Candida albicans in vitro. Methods The sensitivity of 8 strains of Candida albicans to FLC was assessed by determining their minimal inhibitory concentration （MIC） using broth microdilution method. FLC-tolerant strains were screened from FLC-sensitive strains by disk diffusion assay. The effect of BBR combined with FLC on FLC-tolerant Candida albicans was investigated by disk diffusion assay. Results All eight strains of Candida albicans exhibited sensitivity to FLC, with minimal inhibitory concentration （MIC₅₀） values below 0.5 μg/ml. Strains Y0109, 9821, 7879, 7654, and 9296 displayed colony growth in the inhibition zone after 48 h of constant temperature incubation, indicating FLC tolerance. When strains Y0109 and 9821 were subjected to a combination of BBR and FLC, the number of colonies within the inhibition zone decreased progressively with the increase of BBR concentration following a 48 h constant temperature culture. The inhibition zone became clear with the increasing of BBR concentration and increased with the increase of FLC loading, which showed a dose-dependent relationship. Conclusion The BBR combined with FLC demonstrated efficacy against FLC-tolerant strains.

Whole blood transfusion for the resuscitation of trauma patients is not a new concept, with its history dating back to World War I. Due to the significant survival benefits of early intervention with whole blood, an increasing number of countries and regions are using whole blood for pre-hospital resuscitation of patients with traumatic haemorrhage. Whole blood containing low-titer anti-A and anti-B antibodies is known as low-titer group O whole blood. The safety of transfusion of low-titer group O whole blood has been proven in military and local trauma centers in some countries. The use of low-titer group O whole blood for pre-hospital trauma care in China will pose new challenges to blood stations that provide whole blood. This paper reviews the selection of group O donors, the setting of anti-A and anti-B titers threshold and their detection, as well as the collection, preparation and storage of whole blood.

[Objective] To evaluate the clinical application value of intrauterine perfusion with platelet-rich plasma (PRP) combined with in vitro fertilization-frozen-thawed embryo transfer (IVF-FET) in patients with chronic endometritis (CE). [Methods] A randomized controlled trial (RCT) was conducted, enrolling 60 CE patients undergoing artificial cycle frozen embryo transfer at our hospital from January 2022 to January 2024. Participants were randomly divided into three groups: Group A (routine frozen embryo transfer, n=20), Group B (routine frozen embryo transfer + one PRP intrauterine perfusion, n=20), and Group C (routine frozen embryo transfer + two PRP intrauterine perfusions, n=20). Endometrial thickness during the transformation and transplantation phases, uterine artery pulsatility index (PI), resistance index (RI), systolic peak velocity/end-diastolic velocity (S/D) ratio during transplantation, serum levels of IL-2, IL-4, IL-6, IL-10, and TNF-α during transplantation, as well as biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and early miscarriage rate were compared across groups. [Results] No significant differences in endometrial thickness were observed among the three groups during the transformation phase (P>0.05). During the transplantation phase, endometrial thickness in Groups C and B was significantly higher than in Group A[9.54 (8.96-10.22) and 8.90 (8.34-9.72) vs 8.37 (7.89-8.75) mm, P<0.05], with Group C showing greater thickness than Group B (Z=3.733, P<0.05). Endometrial thickness in Groups C and B during transplantation was significantly increased compared to their respective transformation phases (Z=2.191, 2.462; P<0.05). Groups C and B exhibited lower PI, RI, and S/D values than Group A[PI:1.87 (1.77-1.97), 1.94 (1.88-2.15) vs 2.43 (2.35-2.49); RI:0.75 (0.73-0.77), 0.78 (0.75-0.81) vs 0.84 (0.83-0.86); S/D:2.61 (2.33-3.42), 3.01 (2.20-3.93) vs 3.72 (3.06-4.49); P<0.05]. Group C demonstrated lower PI and RI than Group B (P<0.05). IL-2 levels in Groups C and B were higher than in Group A[3.88 (2.71-5.01), 3.59 (2.73-4.38) vs 3.16 (2.11-3.25) ng/L, P<0.05], while IL-4, IL-6, IL-10, and TNF-α levels were significantly lower (IL-4: Z=1.428, 2.421; IL-6: Z=1.754, 2.435; IL-10: Z=1.754, 2.854; TNF-α: Z=1.961, 1.765; P<0.05). Group C had lower IL-6 levels than Group B (Z=3.976, P<0.05). Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate in Group C were significantly higher than in Group A (75% vs 40%, 70% vs 35%, 60% vs 20%, P<0.05). No significant differences in early miscarriage rates were observed among the groups (χ²=3.750, P>0.05). [Conclusion] Intrauterine autologous PRP perfusion in CE patients enhances pregnancy and live birth rates, improves pregnancy outcomes post-FET, and demonstrates superior efficacy in endometrial repair and receptivity with two PRP perfusions compared to a single perfusion. This provides a safe and effective therapeutic option for optimizing outcomes in CE patients with prior implantation failure.

To investigate the awareness of cognitive impairment disorders among residents of the Xizang Autonomous Region and its influencing factors, thereby providing a basis for targeted prevention and treatment efforts.

BACKGROUND:Anthocyanin is one of the most important active components in Lycium ruthenicum Murr,which has antioxidant and immunomodulatory effects.CD146+human adipose-derived pericytes/perivascular cells(CD146+hAD-PCs)are the progenitors of bone marrow mesenchymal stem cells,which can promote the proliferation and differentiation of hematopoietic stem/progenitor cells in vitro.The support effect of anthocyanin in combination with CD146+hAD-PCs on umbilical cord blood hematopoietic stem/progenitor cells remains to be studied. OBJECTIVE:To investigate the supporting effect of anthocyanins in Lycium ruthenicum Murr(ALRM)combined with CD146+hAD-PCs on umbilical cord blood CD34+hematopoietic stem/progenitor cells(UCB CD34+HSPCs)in vitro. METHODS:The CCK-8 assay was used to detect the effect of different concentrations(0,200,400,600,800,1 000 mg/L)of ALRM on the proliferation of CD146+hAD-PCs.Flow cytometry was used to detect the effect of ALRM on the cell cycle of CD146+hAD-PCs.The co-culture experiments were divided into blank group,ALRM group,CD146+hAD-PCs group,and ALRM+CD146+hAD-PCs group to analyze the in vitro supporting effect of ALRM combined with CD146+hAD-PCs on UCB CD34+HSPCs.The number of expanded cells and the number of colony-forming units were compared at 1,2,and 4 weeks of co-culture.The immunophenotype of cells was detected by flow cytometry.The level of cytokines was detected by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION:(1)The cell viability of CD146+hAD-PCs was highest at an ALRM concentration of 200 mg/L,the proportion of G0/G1 phase cells decreased and the proportion of S and G2/M phase cells increased in CD146+hAD-PCs(P<0.01).(2)The change in number of UCB CD34+HSPCs cells in the ALRM+CD146+hAD-PCs group was higher than that in the ALRM group at 1,2,and 4 weeks of co-culture(all P<0.05),and higher than that in CD146+hAD-PCs group at 2 and 4 weeks of co-culture(all P<0.05).The number of cells in the ALRM group and blank group decreased gradually with the extension of co-culture time.(3)Colony forming capacity and immunophenotype analysis:The number of colony-forming units in the ALRM+CD146+hAD-PCs group was higher than that in the CD146+hAD-PCs group and ALRM group at 1 and 2 weeks of co-culture(P<0.05).The proportion of CD45+and CD34+CD33-cells in the ALRM+CD146+hAD-PCs group was higher than that in the CD146+hAD-PCs group at 1 and 2 weeks of co-culture(all P<0.01).(4)Changes in cytokines:Interleukin-2 level in the ALRM+CD146+hAD-PCs group was higher than that in the ALRM and CD146+hAD-PCs groups(P<0.05).The interleukin-3 content of the ALRM+CD146+hAD-PCs group was higher than that of the CD146+hAD-PCs group at 2 and 4 weeks(P<0.05).The expression level of granulocyte colony-stimulating factor in the ALRM+CD146+hAD-PCs group was higher than that in the CD146+hAD-PCs group at 1 week,and higher than that in the ALRM group and CD146+hAD-PCs group at 2 weeks(P<0.01).Interferon-γ content in the ALRM group and ALRM+CD146+hAD-PCs group was lower than that in the CD146+hAD-PCs group at 1,2,and 4 weeks of co-culture(P<0.01).(5)Due to the absence of stromal cells in the blank group,UCB CD34+HSPCs could not be counted after 1 week of co-culture and were not subjected to immunophenotyping,colony analysis,or cytokine assays.(6)In summary,ALRM can promote the expansion of UCB CD34+HSPCs in vitro by promoting CD146+hAD-PCs proliferation and cell cycle transformation,which is of great value in hematopoietic stem cell transplantation.

BACKGROUND:At present,research has only shown that the cervical lordosis ratio can be an important factor in predicting the loss of lordosis curvature after laminoplasty,and no one has studied whether the cervical lordosis ratio,a dynamic level indicator,can be one of the decision-making factors for the selection of posterior cervical surgical procedures. OBJECTIVE:To investigate whether the cervical lordosis ratio,an index of cervical hyperextension and hyperflexion,can be used as a selective index for laminoplasty and laminectomy fusion. METHODS:A retrospective review of 141 patients who had undergone posterior cervical surgery more than one year of follow-up due to multi-level cervical spondylotic myelopathy from December 2015 to March 2020 was performed.Among them,63 patients received laminectomy and fusion(laminectomy and fusion group)and 78 patients received laminoplasty(laminoplasty group).The demographic statistics(gender,age,body mass index,follow-up time),imaging indexes such as C2-7 Cobb angle,C2-7 range of motion,flexion Cobb angle,extension Cobb angle,flexion range of motion and extension range of motion,clinical effect indexes such as Japanese Orthopaedic Association score and visual analog scale score were compared between the two groups.The evaluation index of cervical lordosis alignment change was C2-7 Cobb angle difference before and after operation(ΔCL).Cervical lordosis ratio was equal to 100%×flexion range of motion/C2-7 range of motion.Receiver operating characteristic curve analysis was used to determine the role of cervical lordosis ratio in predicting postoperative severe cervical lordosis loss(ΔCL≤-10°).According to the critical value of cervical lordosis ratio(68.5%),all patients were divided into low cervical lordosis ratio group and high cervical lordosis ratio group.In these two ratio groups,the cervical lordosis alignment index and clinical effect index between the two operation groups were discussed again. RESULTS AND CONCLUSION:(1)Cervical lordosis alignment decreased after laminectomy and fusion and laminoplasty(P=0.039,P=0.002),and cervical lordosis alignment change in laminoplasty group(ΔCL)was greater than that of laminectomy and fusion group,and the difference between the two groups was statistically significant.(2)Based on receiver operating characteristic curve analysis,cervical lordosis ratio in predicting severe cervical lordosis alignment change(ΔCL≤-10°)had good identification ability(area under the curve=0.792).(3)In low cervical lordosis ratio group,there was no significant difference in cervical lordosis alignment change(ΔCL)between laminectomy and fusion group and laminoplasty group(P=0.141).(4)In high cervical lordosis ratio group,the ΔCL of laminoplasty group was greater than that in laminectomy and fusion group(P=0.001),which had a higher probability of postoperative severe cervical lordosis alignment change(ΔCL≤-10°)(43%,29%).(5)It is indicated that cervical lordosis ratio can be used as a decision-making index for the choice of posterior surgery for multi-level cervical spondylotic myelopathy.Laminoplasty can be considered in the low cervical lordosis ratio group,while laminectomy and fusion can be considered in the high cervical lordosis ratio group.

BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Epileptogenesis is a dynamic process of gradual progression from normal developing brain to pathological epileptic brain， which is the latent and budding stage of epilepsy. Combining the understanding of epileptogenesis in children from Western medicine and traditional Chinese medicine （TCM）， we proposed that the viewpoints of constitutional transformation， phlegm pathogen inducing epilepsy， and brain collateral damage， which correspond to key pathological mechanisms， namely gene polymorphism， immunoinflammation， and microvascular dysfunction of the blood-brain barrier， respectively. Based on these insights， strategies for prevention and treatment of epileptogenesis in children， as well as potential research directions are explored.

Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.