Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

In this study,the immunological characteristics of the PhoP protein were explored with a two-component system of Mycobacterium tuberculosis(Mtb).Bioinformatics was used to predict the B and T cell epitopes of the PhoP protein.A re-combinant expression plasmid was constructed by PCR analysis of the phoP sequence and cloning into the prokaryotic expres-sion vector pET-28a(+).Competent Escherichia coli BL21 cells were transformed with the recombinant plasmid and expres-sion was induced with IPTG.The recombinant PhoP protein was purified by affinity chromatography.Serum levels of PhoP-specific antibodies in Mtb-infected mice and tuberculosis(TB)patients were analyzed with an ELISA.BALB/c mice were im-munized with the PhoP recombinant protein by intramuscular injection.Sera of mice were collected and antibody titers were detected with an ELISA and specificity was assessed by West-ern blot analysis.Mouse splenocytes were isolated and the pro-portions of IFN-y-positive cells and cytokine levels were detec-ted with an ELISpot and ELISA,respectively.Bioinformatics i-dentified 24 B cell and 11 T cell epitopes of the PhoP protein.A prokaryotic recombinant vector of PhoP was successfully con-structed and the recombinant PhoP protein was obtained by purification.Specific antibody levels to PhoP in sera of Mtb in-fected mice and TB patients increased significantly,with preci-sion of 99.9％and 82.5％,and specificity of 100％,respectively.PhoP protein immunization successfully induced production of specific antibodies in mice.Stimulated by antigens in vitro,IL-2 and IFN-γ levels were significantly increased in the splenocytes of immunized mice.Immunization with the PhoP protein induce a humoral immune response and Thl-dominated cellular immu-nity,indicating that the PhoP protein was immunogenic with diagnostic efficacy for TB.These results lay a foundation to clari-fy the role of PhoP in Mtb infection and application for diagnosis and prevention of TB.

The steps for installation and withdrawal of WYD2000 field surgical lamp were introduced.The failures and causes of broken cross-arm connector of WYD2000 field surgical lamp were analyzed.The problems of WYD2000 field surgical lamp in vulnerability to breaking and difficulty in maintenance were solved by designing and manufacturing a special maintenance tool and optimizing the materials and fixing mode of cross-arm connection.References were provided for main-tenance and improvement of WYD2000 field surgical lamp.[Chinese Medical Equipment Journal,2024,45(4):116-118]

Objective To explore the effect of a R language-based autoregressive integrated moving average(ARIMA)model for predicting the consumption of medical consumables.Methods The monthly consumption data of a certain type of pre-filled flush syringe from July 2018 to June 2023 was selected as the sample data,which underwent smoothness test and difference operation with R language.An ARIMA model was established and the optimal model was determined according to the Akaike and Bayesian information criteria.The corresponding data of the third quarter of 2023 was used as the validation set to predict the consumption,and the prediction result was compared with the actual values to evaluate the prediction effect of the ARIMA model.Results The ARIMA model with the best fitting was ARIMA(0,1,1)(1,0,0)12,all the predicted data were within 95％confidence interval,and its mean absolute percentage error MAPE was 9.92％.P-value proved to be higher than 0.05 when the residual series were tested using the Ljung-Box statistics,which meant the prediction result was satisfactory.Conclusion The R language-based ARIMA model behaves well in predicting the consumption of medical consumables,and provides references for demand planning,budgeting,purchasing and management of medical consumables.[Chinese Medical Equipment Journal,2024,45(10):84-87]

With the development of small-molecule immunotherapy drugs, its combination with the programmed cell death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibodies would provide a new opportunity for cancer treatment. Therefore, targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity and considered as the next generation of tumor immunotherapy. In the present study, we investigated the anti-tumor role of salvianolic acid B (SAB) by regulating the PD-L1 level in tumors. Changes of total PD-L1 and membrane PD-L1 levels were determined by Western blot, flow cytometry and PD-1/PD-L1 interaction assays. The expression of mRNA level of PD-L1 was detected by real-time PCR. The cytotoxicity of activated peripheral blood mononuclear cell (PBMC) cells toward co-cultured tumor cells was measured by cell impedance assay and crystal violet experiment. Surface plasma resonance technique was used to analyze the direct interaction between SAB and ubiquitin carboxyl-terminal hydrolase 2 (USP2). The antitumor effect of SAB in vivo was examined by C57BL/6 mice bearing MC38 xenograft tumor (all animal experiments were conducted in accordance with the Animal Ethics Committee of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences). Western blot and flow cytometry assay showed that SAB can significantly downregulate the abundance of PD-L1 in RKO and PC3 cells in dose- and time-dependent manner. PD-1/PD-L1 binding assay revealed that SAB reduces the binding of tumor cells to recombinant PD-1 protein. Mechanism studies revealed that SAB can bind directly to USP2 protein and inhibit its activity, thus promote the ubiquitin-proteasome pathway degradation of PD-L1 proteins. In addition, Cell impedance and crystal violet staining indicated that SAB enhances the killing activity of co-cultured PBMC cells toward tumor cells. MC38 tumor transplanted mouse experiments revealed that SAB treatment displayed significant suppression in the growth of MC38 tumor xenografts in C57BL/6 mice with an inhibition rate of 63.2% at 20 mg·kg^-1. Our results demonstrate that SAB exerts its anti-tumor activity by direct binding and inhibiting the activity of USP2 and reducing the PD-L1 level. Our study provides an important material basis and scientific basis for the potential application of SAB in tumor immunotherapy drug targeting USP2-PD-L1 axis.

AIM: To compare the visual effect of patients with presbyopia corrected by bifocal(AtLisa tri 809MP)intraocular lens(IOL)and trifocal(AtLisa tri 839MP)IOL implantation.METHOD:A total of 40 patients(51 eyes)who underwent cataract phacomulsification surgery in our hospital were collected, and they were retrospectively analyzed and divided into group A and group B. The group A with 20 patients(25 eyes)implanted the bifocal 809MP IOL, while the group B with 20 patients(26 eyes)implanted the trifocal 839MP IOL. The uncorrected distance visual acuity(UDVA), uncorrected intermediate distance visual acuity(UIVA), uncorrected near distance visual acuity(UNVA), and the defocus curve of the patients in two groups were measured at 3mo after surgery. Additionally, statistical analysis was carried out through satisfaction questionnaire.RESULT:There were no significant differences in the UDVA and best corrected visual acuity(BCVA)between the two groups at 3mo after surgery(P>0.05). In group B, the UIVA(80cm)was significantly better than that in group A(P<0.01); there was no statistically significant differences in the UNVA of group A and B(P>0.05). The defocus curve analysis at 3mo after surgery revealed that the group A had double peaks at 0D and -3D; while the group B had double peaks at 0D and -2.5D. Patients in the two groups showed different degrees of halo, glare and other optical manifestation, but the overall satisfactions and the near vision satisfactions were higher.CONCLUSION: Two types of IOL can provide patients with full range of vision that including both near and far distance visual acuity. Both of the AtLisa tri 839MP IOL and 809MP IOL can provide good near vision, while the trifocal IOL is more suitable for intermediate distance vision.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

OBJECTIVE: To observe the effect of acupotomy on the morphology and ultrastructure of rectus femoris muscle in rabbits with knee osteoarthritis and to reveal the possible therapeutic mechanism involved in the effect of acupotomology on the treatment of knee osteoarthritis(KOA). METHODS: Twenty-four male New Zealand rabbits aged 6 months and weighed (2.0±0.5) kg were randomly divided into blank group, model group and acupotomy group, 8 rabbits in each group. KOA model was established by modified Videman method with left hind limb extended plaster immobility for 6 weeks. In acupotomy group, the transfascial focal points of quadriceps femoris muscle were released by acupotomy under the guidance of Jingjin theory for 4 times and once a week, and the treatment points include Hedingci, Binwaixia, Binneixia. Blank group and model group were fed normally without intervention. One week after the end of the intervention, the pennation angle(PA), muscle thickness(MT), cross-sectional area(CSA) and strain ratio(SR) of rectus femoris were measured by ultrasound. HE staining was used to observe the changes of the tissue morphology, the number of muscle fibers and the average area of muscle fibers. The myofibril of rectus femoris, sarcomere and myofilament were observed by transmission electron microscope. RESULTS: The PA of rectus femoris muscle in the blank group was (9.05±0.21)°. The MT was(1.09±0.09) cm and the CSA was(1.30±0.01) cm². The PA of rectus femoris muscle in the model group was (3.06±0.15)°. The MT was (0.71±0.02) cm and the CSA was(0.77±0.02) cm². The PA of rectus femoris muscle in the acupotomy group was (6.94±0.28)°. The MT was (0.80±0.05) cm and the CSA was(0.94±0.03) cm². The muscle PA, MT and CSA of rectus femoris in the model group were significantly smaller than those in the blank group (P<0.05). Those in acupotomy group were significantly increased compared with those in model group (P<0.05). The SR of rectus femoris muscle was 1.19±0.02 in the blank group, 3.50±0.05 in the model group and 1.99±0.07 in the acupotomy group. The elastic SR of the model group was significantly higher than that of the blank group (P<0.05). These in acupotomy group was significantly lower than that in model group(P<0.05). The results of HE staining showed:in blank group, the fascicles of rectus femoris were arranged neatly, the number of beam of muscle fibers within the fixed visual field was 94.38±3.50 and the average CSA was(0.75±0.22) mm². In model group, the fascicles of rectus femoris with different sizes were disorganized with a small amount of inflammatory cell infiltration, the number of beam of muscle fibers within the fixed visual field was 196.63±2.62 and the average CSA was(0.26±0.03) mm². Compared to the blank group, a significant increase in the number of muscle fibers in the fixed field in the model group (P<0.05) and the average CSA decreased significantly(P<0.05). In acupotomy group, the rectus femoris fascicles in the acupotomy group tended to be arranged in a more orderly manner, with the inflammatory cells decreased, the number of beam of muscle fibers within the fixed visual field was 132.88±4.61 and the average CSA was(0.70±0.07) mm². Compared to the model group, a significant decrease in the number of muscle fibers in the fixed field in the model group(P<0.05) and the average CSA increased significantly(P<0.05). The results of transmission electron microscope showed:compared with the blank group, the overall arrangement of the myofibrils of the rectus femoris in the model group was less structured. There was fracture between the muscle fibers and the sarcomere, the myofilaments were disordered, and the fracture of the Z line was discontinuous. Compared with the model group, the myofibrillar texture of rectus femoris in acupotomy group was clearer, and the Z line was more continuous. CONCLUSION Based on the jingjin theory, the release of quadriceps femoris by acupotomy can effectively improve the morphology and structure of rectus femoris, and promote the repair and reconstruction of chronic skeletal muscle injury in rabbits with KOA, which may be one of the mechanisms of acupotomy in the treatment of KOA.
Acupuncture Therapy ; Animals ; Humans ; Male ; Muscle, Skeletal ; Osteoarthritis, Knee/therapy* ; Quadriceps Muscle ; Rabbits ; Ultrasonography

OBJECTIVE: To explore the ultrasonic anatomical characteristics and needle-knife insertion approach of common tendon lesions in knee osteoarthritis (KOA), so as to provide the references for accurate release of KOA by needle- knife along tendon lesions based on meridian sinew theory. METHODS: Sixty patients with one-knee KOA were selected. High-frequency musculoskeletal ultrasound was used to collect sonograms at the anatomical positions of "Hedingci" "Binwaixia" "Binneixia" and "Yinlingshang". The anatomic levels were marked on the sonograms. The anatomic levels and sonographic features of lesions were compared and analyzed, and the relevant data of needle-knife simulation approach was measured. RESULTS: The "Hedingci" lesions were mainly located at the attachment of quadriceps tendon to patella and suprapatellar bursa. The "Binwaixia" and "Binneixia" lesions were mainly located at the attachment of retinaculum patellae laterale and retinaculum patellae mediale to patella and infrapatellar fat pad. The "Yinlingshang" lesions were mainly located at the attachment of goose foot tendon to medial tibial condyle and bursa of goose foot. With "Hedingci" as an example, when the needle-knife entry point was 1 cm above the patella, the attachment of quadriceps tendon to patella was released, and the average depth of needle-knife was (3.60±0.10) cm, and the needle body was perpendicular to the skin. The average depth of needle-knife for releasing suprapatellar bursa was (2.35±0.17) cm, and the needle body was 45° towards head. CONCLUSION The musculoskeletal ultrasound could clearly show the local detailed anatomical level, ultrasonic characteristics and anatomical level of common tendon lesions of KOA, and could improve the accuracy of needle-knife along tendon lesions with non-direct vision, which has important reference value for needle-knife medical standardization and standardized operation.
Humans ; Knee Joint/surgery* ; Meridians ; Osteoarthritis, Knee/surgery* ; Patella ; Tendons/surgery* ; Ultrasonography