Objective To evaluate the efficacy and safety of Shenbao tablet in the treatment of kidney-yang deficiency syndrome.Methods Patients with kidney-yang deficiency syndrome,will were treated with Shenbao Tablets orally,3 tablets once,3 times a day,and the course of treatment was 56 days or 84 days,depending on the condition.By comparing the clinical efficacy,the changes of symptom scores and syndrome scores before and after treatment,and symptoms remission time,the effectiveness of Shenbao tablet in the treatment of kidney-yang deficiency syndrome was evaluated.The safety was evaluated by adverse reactions.Results There were 339 patients in the 56-day group and 345 patients in the 84-day group.After treatment,the clinical effective rates of the 56-day group and the 84-day group were 91.74％and 97.97％,respectively,and the difference was statistically significant(P＜0.05).In the 56-day group and the 84-day group,the excellent rate were 58.41％and 59.13％,clinical control rates were 18.58％and 27.54％,and the progress rates were 14.75％and 11.30％,respectively.After treatment,the symptom scores of kidney-yang deficiency syndrome were significantly reduced respectively within both groups(P＜0.05).In the 56-day group and the 84-day group,the nocturia scores of were 0.89±1.27 and 0.60±1.03,the soreness of waist scores were 1.31±1.19 and 0.72±1.00,the morning diarrhea scores were 0.28±0.74 and 0.19±0.61,the anaphrodisia scores were 0.65±1.13 and 0.53±0.98,the low spirits scores were 0.29±0.81 and 0.08±0.40,the cold limbs score were 1.09±1.20 and 0.55±0.93,the edema scores were 0.14±0.55 and 0.05±0.30,the bright pale complexion scores were 0.20±0.59 and 0.24±0.65,respectively.There were significant differences in the reduction of each symptom score between the two groups(P＜0.05);the 56-day group had a more significant decrease in the score of cold limbs than the 84-day group.The remaining symptom scores decreased more significantly in the 84-day group.After treatment,the syndrome scores of kidney-yang deficiency syndrome in the two groups were significantly lower than those before treatment(all P＜0.05);the change rates of score in the 56-day group and the 84-day group were(-72.33±24.57)％and(-78.77±19.53)％,respectively,and the difference was statistically significant(P＜0.05).The self-reported time to first symptom relief was(14.85±7.18)days in the 56-day group and(14.10±7.78)days in the 84-day group,with no significant difference(P＞0.05).The incidence of adverse reactions of Shenbao tablets was 5.37％,mainly reflected in hepatobiliary system diseases,gastrointestinal system diseases and various examination abnormalities.Conclusions After taking Shenbao tablets for 2 to 3 months,the clinical symptoms of kidney-yang deficiency were better improved,and the improvement was more significant after 3 months of treatment.The security of Shenbao Tablets was good.

ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol^-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective To investigate the clinical effects and pregnancy outcomes of using luteal phase long protocol and GnRH antagonist protocol in patients with polycystic ovary syndrome(PCOS)who have failed their first GnRH antagonist protocol therapy.Methods The clinical data of 163 PCOS patients who underwent IVF/ICSI-ET were retrieved.After the failure of their first GnRH antagonist protocol treatment,they were divided into two groups in the second controlled ovarian hyperstimulation(COH)cycle:Luteal phase long protocol group(n=95)and Gn-RH antagonist protocol group(n=68).A retrospective analysis and comparison of basic clinical data,clinical and laboratory indicators,and pregnancy outcomes between two groups were conducted.Results ① There was no sta-tistically significant difference in basic clinical indicators between two group except LH.② Compared the first and second cycle treatments of patients in the luteal phase long protocol group,the initiation dose of gonadotropin(Gn),total number of Gn days,total Gn usage,estradiol(E2)on the day of hCG injection,number of retrieved eggs,oocyte maturation rate,2PN fertilization rate,2PN cleavage rate,blastocyst formation rate,high-quality blas-tocyst formation rate,and moderate to severe OHSS rate were significantly higher than those in the first GnRH an-tagonist cycle(P＜0.05).The GnRH antagonist protocol group also showed similar improvements.③ The com-parison of the second COH cycle between two groups showed that the total number of Gn days,total Gn usage,and total Gn cost in the luteal phase long protocol group were significantly higher(P＜0.05),while the E2 and LH on the day of hCG injection,and the maturation rate of eggs were significantly lower than those in the GnRH antagonist protocol group(P＜0.05).However,there was no statistically significant difference in the number of retrieved eggs,2PN fertilization,2PN cleavage,blastocyst formation rate,high-quality blastocyst formation rate,and OHSS rate between the two groups;④ The comparison of fresh transplantation cycles for the second COH cycle between the two groups showed that the luteal phase long protocol fresh transplantation rate,implantation rate,clinical preg-nancy rate,and live birth rate were slightly higher than those of the GnRH antagonist protocol group,but the differ-ence was not statistically significant.Comparing the outcomes of pregnancy following the initial frozen-thawed em-bryo transfer(FET)between two groups,the biochemical pregnancy rate and clinical pregnancy rate of the GnRH antagonist protocol group were higher than those of the luteal phase long protocol group(P＜0.05).However,no significant statistical variations were found in implantation rate,live birth rate,neonatal gestational age,and birth weight.Conclusion For PCOS patients who fail the first GnRH antagonist protocol,an appropriate increase in the initiating dose and usage of Gn can achieve satisfactory pregnancy outcomes with both protocols.Compared with change to a luteal phase long protocol,reusing the GnRH antagonist protocol still maintains its long-standing advan-tages,such as shorter total Gn days,lower costs,and better patient compliance.

Due to the diverse application forms of Chinese herbal medicine products,the wide range of users,and the complex conditions of medication in China,adverse events including herb-induced liver injury(HILI)occur frequently in recent years.In order to further understand HILI and standardize its risk management and prevention and treatment measures,this article discusses the risk management,clinical evaluation,prevention,and treatment of HILI based on related clinical research advances and experience in recent years.In the multiple links of traditional Chinese medicine including production and clinical application after marketing,the establishment of a comprehensive control system is of great importance for the prevention and treatment of HILI and other adverse events,involving product quality control,patient safety education,rational drug use by clinicians,regular monitoring,and graded and classified treatment,which provides a reference for the rational and safe clinical use of Chinese herbal medicine in the future.

Objective To investigate the mechanism of circadian clock protein Bmal1(Bmal1)on renal injury with chronic periodontitis,we established an experimental rat periodontitis model.Methods Twelve male Wistar rats were randomly divided into control and periodontitis groups(n=6,each group).The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires,whereas the control group re-ceived no intervention measures.After 8 weeks,clinical periodontal parameters,including probing depth,bleeding index,and tooth mobility,were evaluated in both groups.Micro-CT scanning and three-dimensional image recon-struction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption.Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin(HE)and periodic acid-Schiff(PAS)staining.Renal function indicators,such as creatinine,albumin,and blood urea nitrogen levels,and oxida-tive stress markers,including superoxide dismutase,glutathione,and malondialdehyde levels,were measured using bio-chemical assay kits.MitoSOX red staining was used to detect reactive oxygen species(ROS)content in the kidneys.The gene and protein expression levels of Bmal1,nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in rat renal tissues were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)and immuno-histochemical staining.Results Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group.Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group.The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress,whereas the renal function levels showed abnormalities without statistical significance.Mito-SOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group,and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1,Nrf2,and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend.Conclu-sion Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.

Objective This study aims to explore changes in uncoupling protein 2(UCP2)in experimental periodonti-tis-associated renal injury induced by ligation and investigate the effect of UCP2 on renal injury induced by periodontitis.Methods Twelve Wistar male rats were randomly divided into two groups:control and periodontitis groups.A periodon-tal model was built by ligating the maxillary first molars area with 0.2 mm orthodontic ligature wire.After 8 weeks,the in-traoral condition of the rats was observed and periodontal clinical indices such as gingival bleeding index(BI),periodontal probing depth(PD),and tooth mobility(TM)were detected.The maxillary bone was scanned by Micro CT to observe the alveolar bone resorption.The tissue mineral density(TMD),bone mineral density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular bone separation(Tb.Sp)were recorded,and the distance from the enamel bone boundary to the alveolar crest(CEJ-ABC)of the maxillary first molar was measured.The oxidative stress indexes such as malondialdehyde,glutathione(GSH),and superoxide dismutase(SOD)were detected using frozen rat kidney tissue.The gene expression of UCP2,nuclear factor erythroid 2-related factor 2(Nrf2),and peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)was observed by quantitative real-time polymerase chain reaction(qRT-PCR)test.The gingival tissue of the rats was used for immunohistochemical staining to observe the expression of the UCP2 protein.The fixed rat kidney tissue was used for hematoxylin-eosin(HE),periodic acid-schiff(PAS),MitoSOX Red,JC-1,and immu-nohistochemical staining to observe the renal histopathology,the level of reactive oxygen species(ROS),the level of mito-chondrial membrane potential,and the expression of UCP2,Nrf2,and PGC-1α protein.Rat serum was collected to detect renal function indices,namely,blood urea nitrogen(BUN),creatinine(Cre),and albumin(Alb).Results Compared with the control group,the periodontitis group showed red,swollen,and soft gingival tissue,with gingival probing bleeding,periodontal PD increased,tooth loosening,alveolar bone resorption,decreased TMD,BMD,BV/TV,and Tb.Th indices,and increased Tb.Sp index,CEJ-ABC,and gingival UCP2 protein expression.Compared with the control group,the levels of MDA and ROS in the kidney tissue of periodontitis rats and the gene and protein expression of UCP2 increased,and the levels of MMP,GSH,and SOD and the gene and protein expression of Nrf2 and PGC-1α decreased.Renal functional indi-ces,namely,BUN,Cre,and Alb,were not significantly different between the two groups.Conclusion UCP2 may play a role in renal injury induced by periodontitis through oxidative stress.

Objective To observe the clinical efficacy of citicoline sodium tablets combined with huperzine A tablets in the treatment of patients with cognitive impairment after stroke,and to explore the influence on neurological function and serum levels of vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF).Methods Patients with cognitive impairment after stroke were classified into control group and treatment group according to cohort method.The control group was given oral administration of huperzine A tablets 0.1-0.2 mg for twice a day,while the treatment group was given 0.2 g citicoline sodium tablets orally for three times a day on the basis of the control group.Both groups of patients were treated for 12 weeks.The clinical efficacy,cognitive function[Mini-Mental State Examination(MMSE),National Institute of Health stroke scale,Barthel index],neurological function and daily living ability and serum vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)levels were compared and safety was evaluated.Results One hundred patients were enrolled in the experimental group and the control group.After treatment,the total effective rates in treatment group and control group were 92.00％(92 cases/100 cases)and 75.00％(75 cases/100 cases)with significant difference(P＜0.05).The MMSE scores in treatment group and control group after treatment were(23.40±2.43)and(19.35±2.51)points;the scores of National Institutes of Health Stroke Scale were(12.25±1.24)and(15.84±1.61)points;the Barthel Index scores were(71.14±8.60)and(64.26±8.33)points;VEGF levels were(191.52±14.80)and(125.73±11.48)pg·mL-1;BDNF levels were(9.47±1.59)and(8.01±1.35)ng·mL-1.There were statistically significant differences in the above indexes between the treatment group and the control group(all P＜0.05).The adverse drug reactions in the treatment group were mainly dizziness and nausea,and the adverse drug reactions in the control group were mainly dizziness and nausea.The incidence rates of adverse drug reactions in treatment group and control group were 8.00％(8 cases/100 cases)and 5.00％(5 cases/100 cases)(P＞0.05).Conclusion Citicoline sodium tablets combined with huperzine A tablets have a definite efficacy in the treatment of patients with cognitive impairment after stroke,and it has a significant improvement effect on cognitive function and neurological function of patients,with good safety.

Objective To observe the clinical efficacy and safety of alteplase combined with rivaroxaban in the treatment of acute deep vein thrombosis(DVT)in elderly obese patients.Methods Elderly obese patients with DVT were divided into control group and treatment group according to random number table method.The control group was treated with 10 mg·d-1 rivaroxaban tablets orally.The treatment group was treated with 0.9 mg·kg-1·d-1 alteplase on the basis of the control group.Both groups were treated for 1 week.Clinical efficacy,coagulation function indexes,lower limb venous blood flow mechanics indexes,inflammatory factors and vascular endothelial function related indexes,relative expression level of miR-374b-5p,occurrence of adverse drug reactions and recurrence within 3 months were compared between the two groups.Results A total of 80 patients were enrolled in the treatment group and the control group,respectively.After treatment,the total effective rate of treatment group and control group were 92.50％(74 cases/80 cases)and 81.25％(65 cases/80 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the fibrinogen levels of treatment group and control group were(3.58±0.83)and(3.91±1.04)g·L-1,respectively;D-dimer levels were(2.18±0.74)and(2.49±0.93)μg·mL-1,respectively;platelet activating factor were(115.42±10.43)and(119.74±11.37)μg·L-1,respectively;prothrombin time were(12.95±1.16)and(13.41±1.27)s,respectively;the maximum blood flow velocity were(29.19±6.74)and(26.93±4.58)cm·s-1,respectively;the blood flow were(92.17±9.61)and(88.63±8.75)mL·min-1,respectively;endothelial vasoconstricting peptide-1 were(51.97±4.86)and(54.02±4.92)pg·mL-1;the relative expression levels of miR-374b-5p were 2.18±0.73 and 2.49±0.85,respectively.The above indexes of the treatment group were statistically significant compared with the control group(all P＜0.05).Bleeding symptoms were the main adverse drug reactions in both groups.The total incidence of adverse drug reactions in treatment group and control group was 10.00％and 13.75％,respectively,with no statistical significance(P＞0.05).The 3-month recurrence rates of treatment group and control group was 6.25％and 16.25％,respectively,and the difference was statistically significant(P＜0.05).Conclusion Alteplase combined with rivaroxaban has good clinical efficacy in the treatment of elderly obese patients with DVT,which can improve the blood flow of patients,reduce inflammatory response,and has high safety.

Objective To develop a damage control operation(DCO)simulation training platform for traumatic brain injury(TBI)in wartime based on mixed reality to open up a new path for surgical skills training of military surgeons.Methods The platform mainly consisted of wartime TBI DCO simulation training software,a surgical manikin and a HoloLens 2 MR device.The simulating training software was developed with C# language and the technologies of MR,basic gestures,spatial scanning positioning and etc on the basis of constructed surgical decision-making training system,virtual surgical environment and functional modules.The surgical manikin was customized with reference to the standard body type of an adult male with a height of 180 cm,and an electronic chip was developed and placed inside the head of the manikin to execute data matching with the simulation training software.The simulation training software was installed and run in the HoloLens 2 MR device to realize TBI DCO simulation training on the virtual reality interactive model.Results The platform developed implemented the functions of virtual reality interactive model reset positioning,operation simulation training,examination and on-site demonstration,which gained advantages in stimulating learning interest and facilitating risk-free,time-and space-indepen-dent,immersive and interactive learning and was generally recognized by the trainees.Conclusion The simulation training platform can be a supplementary to other training means to improve the ability of military surgeons in damage control operation.[Chinese Medical Equipment Journal,2024,45(2):17-21]