Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Objective:To investigate the expression of SAPCD2 in esophageal squamous cell carcinoma (ESCC) tissues and its effects on the biological function of ESCC cells in vitro, as well as the possible molecular mechanisms.Methods:By using the Gene Expression Profile Interaction Analysis (GEPIA) platform, the transcriptional level expressions of SAPCD2 in 182 ESCC samples and 286 normal esophageal tissue samples from the Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) database were analyzed. Immunohistochemical (IHC) staining was performed on clinical tissue chips of ESCC patients, and staining scores were evaluated. The expression differences of SAPCD2 protein between 61 cancer tissues and the paired adjacent tissues with the complete clinical data, as well as the distribution of patients with SAPCD2 high expression among patients stratifies by different clinicopathological features were compared. ESCC cell line KYSE-150 was transfected with plasmids carrying SAPCD2 sequence and short hairpin RNA sequence targeting SAPCD2, respectively, which was treated as the SAPCD2 overexpression group and SAPCD2 knockdown group; and the cells transfected with empty plasmids and plasmids carrying negative RNA sequence were treated as the overexpression control group and the knockdown control group. CCK-8 method (expressed with the absorbance value) and plate clone formation assay were used to detect the cell proliferation ability. Cell migration was detected by using cell scratch assay and Transwell cell migration assay were used to detect the cell migration ability. The reverse-real time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the mRNA levels of SAPCD2, matrix metalloproteinase-9 (MMP9), proliferating cell nuclear antigen (PCNA), and Vimentin in cells of all groups. Western blotting was used to detect the expression levels of SAPCD2 protein and proteins related to cell proliferation, invasion, metastasis, and AKT signaling pathway.Results:GEPIA platform analysis showed that the transcriptional expression level of SAPCD2 in ESCC tissues was higher than that in adjacent tissues, and the difference was statistically significant ( P < 0.01). IHC staining showed that the staining score of SAPCD2 protein in cancer tissues was higher than that in adjacent tissues [(8.2±2.8) points vs. (2.2±1.7) points], and the proportion of patients with positive SAPCD2 protein (staining score > 0 point) in cancer tissues was higher than that in adjacent tissues [95.1% (58/61) vs. 57.4% (35/61)], and the differences were statistically significant (all P < 0.001), while there were no statistically significant differences in the distribution of the high expression of SAPCD2 protein (staining score > 3 points) patients stratified by gender, age, tumor size, pathological grade, and T stage, N stage and M stage (all P > 0.05). CCK-8 assay showed that the absorbance value of KYSE-150 cells in the SAPCD2 overexpression group after 96 h of culture was higher than that in the overexpression control group, while the absorbance values of the SAPCD2 knockdown group after 72 h and 96 h of culture were lower than those in the knockdown control group, and the differences were statistically significant (all P < 0.05). The plate clone formation assay showed that the number of colonies of KYSE-150 cells cultured for 14 d in the SAPCD2 overexpression group was more than that in the overexpression control group [(800±30) vs. (458±47)], and that in the SAPCD2 knockdown group was less than that in the knockdown control group [(52±7) vs. (81±2)], and the differences were statistically significant (all P < 0.05). The cell scratch assay showed that after 24 h of culture, the scratch width of KYSE-150 cells in the SAPCD2 overexpression group was narrower than that in the overexpression control group [(51±9) μm vs. (89±7) μm], while that in the SAPCD2 knockdown group was wider than that in the knockdown control group [(120±22) μm vs. (37±10) μm], and the differences were statistically significant (all P < 0.01). Transwell cell migration assay showed that the migration number of KYSE-150 cells in the SAPCD2 overexpression group was more than that in the overexpression control group [(202±18) vs. (50±14)], and that in the SAPCD2 knockdown group was less than that in the knockdown control group [(227±27) vs. (483±16)], and the differences were all statistically significant (all P < 0.01). qPCR assay showed that the mRNA relative expression levels of MMP9, PCNA and Vimentin in KYSE-150 cells in the SAPCD2 overexpression group were all higher than those in the overexpression control group, while those in the SAPCD2 knockdown group were all lower than those in the knockdown control group, and the differences were statistically significant (all P < 0.05). Western blotting showed that the relative expression levels of PCNA and Vimentin proteins in KYSE-150 cells of the SAPCD2 overexpression group were higher than those of the overexpression control group, while the relative expression levels of epithelial cadherin (E-cad) and cleaved cysteine aspartate protease 3 (CASP3) proteins were lower than those of the overexpression control group; however, the expression levels in SAPCD2 knockdown group showed the opposite results, and the differences were statistically significant (all P < 0.05); the relative expression level of phosphorylated AKT (p-AKT) protein in the SAPCD2 overexpression group was higher than that in the overexpression control group, while that in the SAPCD2 knockdown group was lower than that in the knockdown control group, and the differences were statistically significant (all P < 0.01). Conclusions:SAPCD2 is highly expressed at both the transcriptional level and the protein level in ESCC tissues. SAPCD2 promotes the proliferation and migration of ESCC cells in vitro, which may be related to the AKT signaling pathway.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections.Herein,we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering(SERS)and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease(MNase)in serum samples.The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)molecules to SERS-enhanced oxidized TMB(oxTMB),accompanied by the color change from colorless to blue.In the presence of S.aureus,the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads(MBs)to release alkaline phosphatase(ALP),which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away.Using this"on-to-off"triggering strategy,the target S.aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode.Meanwhile,the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis(n=7)and healthy participants(n=3),as well as monitored the prog-nostic progression of the disease(n=2).Overall,benefiting from highly active and dense"hot spot"substrate,MNase-mediated cascade response strategy,and colorimetric/SERS dual-signal output,this methodology will offer a promising avenue for the early diagnosis of S.aureus infection.

ObjectiveTo investigate whether co-activated mesenchymal stem cells（MSCs） exert therapeutic effects against schistosomiasis by modulating macrophage polarization. MethodsTwenty adult male Balb/c mice were randomly divided into four groups： uninfected， infected， MSC-treated， and MSC^TLR4+IFN-γ-treated groups. The Schistosoma japonicum infection model was established via abdominal patch method with cercariae. At week 5 post-infection， praziquantel was administered orally for antiparasitic treatment. At week 6， mice received either MSCs treatments （with or without pre-activation） or no treatment. Body weight changes were monitored weekly. Hepatic pathological alterations were evaluated via HE and Masson staining. RT-qPCR was used to assess α-SMA and collagen （Col-I， Col-Ⅲ） mRNA levels to quantify fibrosis. The mRNA levels of hepatic inflammatory cytokines and matrix metalloproteinases（MMP） were analyzed to explore fibrotic mechanisms. The expressions of i-Nos and Arg-1 in liver tissues were detected by RT-qPCR， and the ratio of M1 or M2 macrophages was detected by immunofluorescence staining， aiming to analyze the correlation between MSCs treatment and macrophage polarization. An in vitro co-culture system validated direct MSC-macrophage interactions. ResultsCompared with the infected group， the MSC^TLR4+IFN-γ group exhibited increased body weight gain （P< 0.01）， reduced hepatic granulomatous lesion area （P< 0.001）， and decreased α-SMA， Col-I， and Col-Ⅲ mRNA levels （P< 0.01）. Additionally， the MSC^TLR4+IFN-γ group showed reduced TNF-α and IL-1β expression （P< 0.05）， as well as elevated MMP2， Mmp9， and MMP13 levels （P< 0.01）. The MSC^TLR4+IFN-γ group showed higher expression of M2 marker Arg-1 mRNA compared with the infection group （P < 0.001） ， while the expression of M1 marker i-Nos decreased （P< 0.05）. Immunofluorescence confirmed a lower i-Nos+ cell ratio （P< 0.05） and higher F4/80⁺CD206⁺ cell ratio （P< 0.000 1） in the MSC^TLR4+IFN-γ group compared with the infection group. In vitro co-culture experiments further demonstrated that MSC^TLR4+IFN-γ promoted Arg-1 expression， suppressed pro-inflammatory cytokine i-Nos and TNF-α levels， consistent with ELISA results. ConclusionsThis study reveals that TLR4 and IFN-γ co-activated MSCs alleviate Schistosoma japonicum-induced hepatic fibrosis， potentially through modulating macrophage polarization toward the M2 phenotype. This mechanism may suppress inflammation and enhance extracellular matrix degradation， providing a therapeutic strategy for schistosomiasis-associated liver fibrosis.

Objective:To investigate the expression of SAPCD2 in esophageal squamous cell carcinoma (ESCC) tissues and its effects on the biological function of ESCC cells in vitro, as well as the possible molecular mechanisms.Methods:By using the Gene Expression Profile Interaction Analysis (GEPIA) platform, the transcriptional level expressions of SAPCD2 in 182 ESCC samples and 286 normal esophageal tissue samples from the Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) database were analyzed. Immunohistochemical (IHC) staining was performed on clinical tissue chips of ESCC patients, and staining scores were evaluated. The expression differences of SAPCD2 protein between 61 cancer tissues and the paired adjacent tissues with the complete clinical data, as well as the distribution of patients with SAPCD2 high expression among patients stratifies by different clinicopathological features were compared. ESCC cell line KYSE-150 was transfected with plasmids carrying SAPCD2 sequence and short hairpin RNA sequence targeting SAPCD2, respectively, which was treated as the SAPCD2 overexpression group and SAPCD2 knockdown group; and the cells transfected with empty plasmids and plasmids carrying negative RNA sequence were treated as the overexpression control group and the knockdown control group. CCK-8 method (expressed with the absorbance value) and plate clone formation assay were used to detect the cell proliferation ability. Cell migration was detected by using cell scratch assay and Transwell cell migration assay were used to detect the cell migration ability. The reverse-real time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the mRNA levels of SAPCD2, matrix metalloproteinase-9 (MMP9), proliferating cell nuclear antigen (PCNA), and Vimentin in cells of all groups. Western blotting was used to detect the expression levels of SAPCD2 protein and proteins related to cell proliferation, invasion, metastasis, and AKT signaling pathway.Results:GEPIA platform analysis showed that the transcriptional expression level of SAPCD2 in ESCC tissues was higher than that in adjacent tissues, and the difference was statistically significant ( P < 0.01). IHC staining showed that the staining score of SAPCD2 protein in cancer tissues was higher than that in adjacent tissues [(8.2±2.8) points vs. (2.2±1.7) points], and the proportion of patients with positive SAPCD2 protein (staining score > 0 point) in cancer tissues was higher than that in adjacent tissues [95.1% (58/61) vs. 57.4% (35/61)], and the differences were statistically significant (all P < 0.001), while there were no statistically significant differences in the distribution of the high expression of SAPCD2 protein (staining score > 3 points) patients stratified by gender, age, tumor size, pathological grade, and T stage, N stage and M stage (all P > 0.05). CCK-8 assay showed that the absorbance value of KYSE-150 cells in the SAPCD2 overexpression group after 96 h of culture was higher than that in the overexpression control group, while the absorbance values of the SAPCD2 knockdown group after 72 h and 96 h of culture were lower than those in the knockdown control group, and the differences were statistically significant (all P < 0.05). The plate clone formation assay showed that the number of colonies of KYSE-150 cells cultured for 14 d in the SAPCD2 overexpression group was more than that in the overexpression control group [(800±30) vs. (458±47)], and that in the SAPCD2 knockdown group was less than that in the knockdown control group [(52±7) vs. (81±2)], and the differences were statistically significant (all P < 0.05). The cell scratch assay showed that after 24 h of culture, the scratch width of KYSE-150 cells in the SAPCD2 overexpression group was narrower than that in the overexpression control group [(51±9) μm vs. (89±7) μm], while that in the SAPCD2 knockdown group was wider than that in the knockdown control group [(120±22) μm vs. (37±10) μm], and the differences were statistically significant (all P < 0.01). Transwell cell migration assay showed that the migration number of KYSE-150 cells in the SAPCD2 overexpression group was more than that in the overexpression control group [(202±18) vs. (50±14)], and that in the SAPCD2 knockdown group was less than that in the knockdown control group [(227±27) vs. (483±16)], and the differences were all statistically significant (all P < 0.01). qPCR assay showed that the mRNA relative expression levels of MMP9, PCNA and Vimentin in KYSE-150 cells in the SAPCD2 overexpression group were all higher than those in the overexpression control group, while those in the SAPCD2 knockdown group were all lower than those in the knockdown control group, and the differences were statistically significant (all P < 0.05). Western blotting showed that the relative expression levels of PCNA and Vimentin proteins in KYSE-150 cells of the SAPCD2 overexpression group were higher than those of the overexpression control group, while the relative expression levels of epithelial cadherin (E-cad) and cleaved cysteine aspartate protease 3 (CASP3) proteins were lower than those of the overexpression control group; however, the expression levels in SAPCD2 knockdown group showed the opposite results, and the differences were statistically significant (all P < 0.05); the relative expression level of phosphorylated AKT (p-AKT) protein in the SAPCD2 overexpression group was higher than that in the overexpression control group, while that in the SAPCD2 knockdown group was lower than that in the knockdown control group, and the differences were statistically significant (all P < 0.01). Conclusions:SAPCD2 is highly expressed at both the transcriptional level and the protein level in ESCC tissues. SAPCD2 promotes the proliferation and migration of ESCC cells in vitro, which may be related to the AKT signaling pathway.

【Objective】 To establish an effective quality monitoring indicator system for blood quality control in blood banks, in order to analyze the quality control indicators for blood collection and supply, and evaluate blood quality control process, thus promoting continuous improvement and standardizing management of blood quality control in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation services, component preparation, blood testing, blood supply and quality control was established. The Questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process was distributed to 17 blood banks in Shandong, which clarified the definition and calculation formula of indicators. The quality monitoring indicator data from January to December 2022 in each blood bank were collected, and 20 quality control indicators data were analyzed by SPSS25.0 software. 【Results】 The average pass rate of key equipment monitoring, environment monitoring, key material monitoring, and blood testing item monitoring of 17 blood banks were 99.47%, 99.51%, 99.95% and 98.99%, respectively. Significant difference was noticed in the pass rate of environment monitoring among blood banks of varied scales(P<0.05), and the Pearson correlation coefficient (r) between the total number of blood quality testing items and the total amount of blood component preparation was 0.645 (P<0.05). The average discarding rates of blood testing or non-blood testing were 1.14% and 3.36% respectively, showing significant difference among blood banks of varied scales (P<0.05). The average discarding rate of lipemic blood was 3.07%, which had a positive correlation with the discarding rate of non testing (r=0.981 3, P<0.05). There was a statistically significant difference in the discarding rate of lipemic blood between blood banks with lipemic blood control measures and those without (P<0.05). The average discarding rate of abnormal color, non-standard volume, blood bag damage, hemolysis, blood protein precipitation and blood clotting were 0.20%, 0.14%, 0.06%, 0.06%, 0.02% and 0.02% respectively, showing statistically significant differences among large, medium and small blood banks(P<0.05).The average discarding rates of expired blood, other factors, confidential unit exclusion and unqualified samples were 0.02%, 0.05%, 0.003% and 0.004%, respectively. The discarding rate of blood with air bubbles was 0.015%, while that of blood with foreign body and unqualified label were 0. 【Conclusion】 The quality control indicator system of blood banks in Shandong can monitor weak points in process management, with good applicability, feasibility, and effectiveness. It is conducive to evaluate different blood banks, continuously improve the quality control level of blood collection and supply, promote the homogenization and standardization of blood quality management, and lay the foundation for comprehensive evaluation of blood banks in Shandong.

【Objective】 To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. 【Methods】 A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. 【Results】 The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P<0.05). The platelet collection rate, incidence of adverse reactions to blood donation, and non-standard whole blood collection rate in large blood banks were significantly lower than those in medium and small blood banks (P<0.05). The average quality monitoring indicators for blood component preparation process of 17 blood banks were as follows: the leakage rate of blood component preparation bags was 0.03% (3/10 000), the discarding rate of lipemic blood was 3.05% (61/2 000), the discarding rate of hemolysis blood was 0.13%(13/10 000). 0.06 case had labeling errors, 8 bags had blood catheter leaks, 2.76 bags had blood puncture/connection leaks, and 0.59 cases had non-conforming consumables. The discarding rate of hemolysis blood of large blood banks was significantly lower than that of medium and small blood banks (P<0.05), and the discarding rate of lipemic blood of large and medium blood banks was significantly lower than that of small blood banks (P<0.05). The average values of quality monitoring indicators for blood supply process of 17 blood banks were as follows: the discarding rate of expired blood was 0.023% (23/100 000), the leakage rate during storage and distribution was of 0.009%(9/100 000), the discarding rate of returned blood was 0.106% (53/50 000), the service satisfaction of hospitals was 99.16% (2 479/2 500). The leakage rate of blood components during storage and distribution was statistically different with that of blood component preparation bags between different blood banks (P<0.05). There were statistically significant differences in the proportion of regular blood donors, incidence of adverse reactions, non-standard whole blood collection rate, 400 mL whole blood collection rate, double platelet collection rate, the blood bag leakage rate during preparation process, the blood components leakage rate during storage and distribution as well as the discarding rate of lipemic blood, hemolysis blood, expired blood and returned blood among large, medium and small blood banks (all P<0.05). 【Conclusion】 The establishment of a quality monitoring indicator system for blood donation services, blood component preparation and blood supply processes in Shandong has good applicability, feasibility and effectiveness. It can objectively evaluate the quality management level, facilitate the continuous improvement of the quality management system, promote the homogenization of blood management in the province and lay the foundation for future comprehensive evaluation of blood banks.

【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ²=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ²=17.927， P<0.01）. The disappearance rate of dry eyes （χ²=8.305）， dull complexion （χ²=4.053）， lassitude （χ²=10.267）， shortness of breath （χ²=8.494）， and dry stool （χ²=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ²=8.382）， fundus changes （χ²=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.