BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

Objective To investigate and assess the risk signals of adverse drug events(ADEs)associated with the post-marketing 4 long-acting anticholinergic antagonists(LAMA),including adionium bromide,glycopyrronium bromide,umeonium bromide,and tiotropium bromide,to provide references for clinically safe prescribing practices.Methods Four LAMA drugs-related ADE records were selected by searching the FAERS database from the first quarter of 2004 to the first quarter of 2024 and standardizing the drug name of adionium bromide,glycopyrronium bromide,umeonium bromide,and tiotropium bromide,with the primary suspected drug as a restriction.Potential ADE signals were mined using the reporting odds ratio(ROR)method,medicines and healthcare products regulatory agency(MHRA)method and Bayesian confidence propagation neural network(BCPNN)method,and Medical Dictionary for Drug Regulatory Activities 26.1 was used to classify the results systematically.Results A total of 80 680 reports of four LAMA drugs-related ADE were collected,including 4 287 reports for aclidinium bromide,3 584 reports for glycopyrronium bromide,3 084 reports for umeclidinium bromide and 69 725 reports for iotropium bromide.The reports predominantly involved female patients(47 725 cases,59.15％)over male patients(27 525 cases,34.11％).The United States emerged as the principal reporting country,with consumers,pharmacists,and physicians as the primary reporters.Serious ADE outcomes included life-threatening conditions,hospitalizations,disabilities,deaths.A total of 902 signals were identified,mainly affecting 27 systems or organs.Specifically,aclidinium bromide(180 signals),glycopyrronium bromide(210 signals),umeclidinium bromide(142 signals),and tiotropium bromide(370 signals)exhibited signals predominantly in the respiratory,thoracic and mediastinal disorders,investigations,injury,poisoning and procedural complications,eye and organ diseases cgastrointestinal disorders.Conclusion When using LAMA drugs for respiratory conditions,clinicians should implement preventive measures to monitor respiratory diseases,thoracic and mediastinal diseases,eye and organ changes and various laboratory examination indicators,to reduce the risk of medication.

In order to obtain polyclonal antibodies against the fibrillar(Fiber)protein of fowl ade-novirus serotype 11(FAdV-11)and investigate its cross-reactivity to different serotypes of FAdV Fiber,the gene encoding the FAdV-11 Fiber protein was cloned into a prokaryotic expression vec-tor pET-32a by homologous recombination technology,then the plasmid was transformed into BL21(DE3)receptor cells,and the purified recombinant protein was used as an immunogen to im-munize rabbits to prepare polyclonal antibody after induced expression,and the cross-reactivity of the polyclonal antibody against different serotypes of FAdV Fiber proteins was identified by West-ern blot and indirect immunofluorescence(IFA).The results showed that the His-FAdV-11-Fiber recombinant protein was mainly expressed as inclusion bodies and was well expressed.Western blot and IFA showed that the prepared polyclonal antibody reacted with the Fiber proteins of FAdV-8a,FAdV-8b,and FAdV-11,but did not with the 2 Fiber of FAdV-4(Fiber 1 and Fiber 2)proteins.In conclusion,in this study,we successfully prepared rabbit polyclonal antibodies against FAdV-11 Fiber and showed that it specifically recognized the Fiber proteins of FAdV-8a,FAdV-8b and FAdV-11,which lays the foundation for further establishment of serological differential diag-nosis of FAdV-11.

Objective To compare the difference and consistency between OPD-Scan Ⅲ and IOL-Master 700 in the measurement of corneal curvature(flat keratometry,K1 and steep keratometry,K2)and horizontal corneal diameter(white-to-white(WTW)distance).Methods Totally 268 patients with 328 eyes(164 right eyes and 164 left eyes)who underwent cataract surgery at the Department of Ophthalmology of the Aerospace Centre Hospital from October 2021 to September 2022 were selected for this study.The K1,K2,and WTW values of the sampled right or left eyes were measured and analyzed using OPD-Scan Ⅲ and IOL-Master 700,respectively.Parameter comparisons were performed through paired t-tests;correlations between parameters were detected through the Pearson correlation analysis;and the Bland-Altman method and intragroup correlation coefficient(ICC)analysis were employed to determine the consistency of parameter measurements between the two instruments.Results The K1 and K2 values measured by OPD-Scan Ⅲ were greater than those measured by IOL-Master 700,while the WTW values were lower than those measured by IOL-Master 700,but the differences were statistically significant(all P＜0.001).K1,K2,and WTW values measured by OPD-Scan Ⅲ were positive-ly correlated with the corresponding values measured by IOL-Master 700,and the differences were statistically significant(all P＜0.001).The proportions of K1,K2,and WTW values outside the 95％limits of agreement for both instruments were within 5％,but the absolute value of the difference in values within the 95％limits of agreement was close to or more than(1.0)D,indicating a sizeable clinical deviation.ICC analysis confirmed a good consistency between K1 and K2 values of the left and right eyes measured by the two instruments(ICC＞0.90).The difference in WTW values measured by the two instruments was significantly correlated with K2 values(both P＜0.05).There were 5 samples(83.33％)outside the positive deviation range of WTW values,of which K2 measured by IOL-Master 700 was above 47.03.Conclusion The OPD-Scan Ⅲ and IOL-Master 700 have been found to have measurement biases when assessing K1,K2 and WTW.In clini-cal practice,the two instruments cannot be interchanged as an alternative to each other.The WTW values measured by IOL-Master 700 are greater than those obtained by OPD-Scan Ⅲ;when K2≥47.03,the WTW values may not be reliably ref-errable.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

BACKGROUND:Most of the biomechanical studies on kyphosis have focused on trunk muscle strength and sagittal plane balance,and little has been reported on the biomechanical response within the spine during kyphosis. OBJECTIVE:To investigate the biomechanical response of the spine during postural kyphosis by simulating the process of postural kyphosis. METHODS:A three-dimensional finite element model of the normal thoracolumbar segment(T1-S1 segment)was established by using the finite element method.10 groups of pure bending loads from 1.15-11.52 N·m were applied using a three-point force system on T1,T6,and T12 vertebrae to simulate the process of postural kyphosis in normal humans.The relationship between the loads and Cobb angle and the biomechanical responses of vertebrae,ribs,and intervertebral discs were analyzed. RESULTS AND CONCLUSION:(1)During postural kyphosis,the Cobb angle size of T1-T12 segments was linearly related to the load size.(2)The maximum stresses on the vertebrae,ribs,and intervertebral discs increased with increasing load.(3)Under the action of 11.52 N·m moment,the maximum stresses on the vertebral body,ribs,and intervertebral disc were found in the front of the T6 vertebral body,the rib head of the 10th pair of ribs,and the right posterior side of the intervertebral disc of the T5-T6 segments.(4)The results of this study suggest that postural kyphosis leads to increased stress on the vertebrae,ribs,and discs,with the most significant increase in stress on the anterior side of the T6 vertebrae,at the rib head of the 10th pair of ribs,and on the anterior side of the disc at the T5-T6 segment,as well as on the posterior side,which may increase the risk of injury to the vertebrae,ribs,and discs,which provides a biomechanical basis for the design of kyphosis orthoses.

Data analysis models may assist the transmission of traditional Chinese medicine （TCM） experience and clinical diagnosis and treatment， and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis， and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases， syndrome elements， evolution of pathogenesis， and syndrome differentiation protocols； knowledge-driven is to make use of data and information to promote decision-making and action processes， and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy， and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research， we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state， and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile， the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained， and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored， so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.

Objective:To explore the effects of phased goal directed fluid therapy (GDFT) during anesthesia surgery on tissue perfusion and cognitive function in patients undergoing radical lung cancer surgery.Methods:A total of 108 lung cancer patients were prospectively selected and randomly divided into a control group and a study group using a random number table method. The control group received classical restrictive liquid therapy, while the study group received staged GDFT. We compared the surgical time, intraoperative blood loss, colloid fluid dosage, crystalloid fluid dosage, total output, and urine volume between two groups of patients; Two groups of patients were compared in terms of oxygenation index (OI), respiratory index (RI), central venous oxygen saturation (ScvO 2), lactate (Lac), central venous arterial carbon dioxide partial pressure difference (Pcv-aCO 2), oxygen supply index (DO 2I), and oxygen uptake rate (O 2ERe) before anesthesia induction (T 0), before single lung ventilation (T 1), 1 hour of single lung ventilation (T 2), immediate resumption of dual lung ventilation (T 3), 30 minutes of dual lung ventilation (T 4), and after surgery (T 5); The Mini Mental State Examination (MMSE) was used to evaluate the cognitive function scores of two groups of patients 1 day before surgery and 1 and 3 days after surgery, while recording the incidence of cognitive dysfunction (POCD) and pulmonary complications (including pulmonary infection, acute lung injury, pulmonary embolism, pulmonary edema, atelectasis, etc.) within 3 days after surgery. Results:The amount of crystal fluid and urine output in the research group was significantly lower than that in the control group, while the amount of colloidal fluid was significantly higher than that in the control group (all P<0.05). The OI of the study group T 1-T 5 was significantly higher than that of the control group, while the RI of T 2-T 5 was significantly lower than that of the control group (all P<0.05). The ScvO 2 of the study group T 1 to T 5 was significantly higher than that of the control group, and the Lac was significantly lower than that of the control group (all P<0.05); The MMSE scores of both groups of patients were significantly lower than those before surgery on day 1 and 3 after surgery, and the MMSE scores of the study group were significantly higher than those of the control group on day 1 and 3 after surgery (all P<0.05). The incidence of POCD within 3 days after surgery in the study group was 16.67%(9/54), lower than 37.04%(20/54) in the control group (χ 2=5.704, P=0.017); The incidence of pulmonary complications in the study group was lower than that in the control group (5.56% vs 22.22%, χ 2=4.955, P=0.026). Conclusions:The application of staged GDFT during anesthesia in patients undergoing radical lung cancer surgery can further improve tissue perfusion, improve microcirculation and oxygen supply-demand balance of systemic organs and tissues, including the brain, alleviate perioperative brain function damage, and reduce the occurrence of postoperative POCD compared to conventional liquid therapy.

This article analyzed the specific path of iron overload affecting EMT "blood countercurrent cell survival/adhesion/invasion/angiogenesis ectopic lesions" from the three aspects of mediating NF-κB and inflammatory reaction, stimulation of abnormal activation of macrophages, and induction of oxidative stress injury; introduced the theoretical connotation of the pathogenesis of "cold coagulation and blood stasis", and briefly described the progress of the pathogenesis of EMT from the perspective of "blood out of menstruation - injury caused by cold pathogenic factors - cold coagulation and blood stasis - long-term accumulation syndrome"; based on the mutual confirmation of "menstruation countercurrent - iron overload microenvironment - cell survival/adhesion/invasion/angiogenesis - ectopic focus" and "blood out of menstruation - cold pathogen injury - cold coagulation and blood stasis - chronic accumulation syndrome", it was believed that starting from iron overload could tap the scientific connotation and microscopic materials of the pathogenesis of "cold coagulation and blood stasis" in EMT, so as to provide new directions and theoretical references for the research of the pathogenesis of EMT and the mechanism of drugs.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.