The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.

AIM To investigate the effects of Huazhuo Jiedu Shugan Formula(HJSGF)on improving learning and memory impairment in a rat model of vascular dementia(VD)via SIRT1/PGC-1α/PPARγ pathway.METHODS The SD rats were randomly divided into the sham control group,the model group,the donepezil group(0.5 mg/kg),and the low-,medium-and high-dose HJSGF groups(2.7,5.4,10.8 g/kg),with 10 rats in each group.The VD rat models established by bilateral common carotid artery permanent ligation(2-VO)had their neurological behavior assessment using the Longa5-point scale,and their modeling success confirmed by the Morris water maze test and their 3-week corresponding dosing of drugs by gavage afterward.After the drug administration,the rats had their spatial memory ability tested through behavioral experiments;their serum levels of IL-18 and IL-1β measured by ELISA;their histopathological changes and neuronal morphology in the hippocampal CA1 region observed by HE staining and Nissl staining;and their hippocampal protein expressions of SIRT1,PGC-1α and PPARγ detected by immunohistochemistry and Western blot.RESULTS Compared with the sham control group,the model group showed prolonged escape latency(P＜0.01);decreased platform crossing times and target quadrant residence time(P＜0.01);disorganized arrangement of hippocampal CA1 neurons,nuclear condensation,reduced Nissl bodies,increased secretion and protein expressions of IL-1β and IL-18(P＜0.01);and reduced hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.01).Compared with the model group,the groups intervened with donepezil or HJSGF showed shortened escape latency(P＜0.05,P＜0.01);increased platform crossing times and target quadrant residence time(P＜0.05,P＜0.01);alleviated damage of the hippocampal CA1 region,reduced secretion and protein expressions of IL-1β and IL-18(P＜0.05,P＜0.01);and elevated hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.05,P＜0.01).CONCLUSION HJSGF may alleviate the inflammatory responses in VD rats and therefore improve their learning and memory impairment by activating the SIRT1/PGC-1α/PPARγ signaling pathway.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To investigate the effect of a G-protein receptor 110(GPR110)ligand on retinal neuroinflam-mation in diabetic mice by regulating the Janus kinase 2/signal transduction and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods This experiment was divided into two parts.(1)Twelve C57BL/6J mice(24 eyes)were randomly divided into the control group,4-week streptozotocin(STZ)induction(STZ4-week)group,STZ 8-week group,and STZ 12-week group,with 3 mice in each group.The diabetic model was induced by intraperitoneal injection of STZ(150 mg·kg-1)in all groups except the control group.The expression of GPR110 and glutamine synthetase(GS)in the retinal tissue of mice was detected by immunofluorescence staining to screen the optimal acting time.(2)Thirty-two C57BL/6J mice(64 eyes)were divided into the control group,STZ 8-week group,the STZ+N-docosahexaenol ethanola-mine(SYN)group,and the STZ+SYN+adeno-associated virus-mediated GPR110(AAV-GPR110)group,with 8 mice in each group,and they were subjected to corresponding treatment.Immunohistochemistry was performed to detect the ex-pression of glial fibrillary acidic protein(GFAP)in mouse retinal tissues.ELISA was performed to detect the level of inter-leukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in mouse retinal tissues.Western blot was performed to detect the ratio of JAK2 to phosphorylated JAK2(p-JAK2)and that of STAT3 to phosphorylated STAT3(p-STAT3).Results(1)GPR110 in the retina of mice in the STZ 4-week group,STZ 8-week group,and STZ 12-week group was mainly expressed in Müller cells.The highest expression intensity of GPR110 was observed in the retina of mice in the STZ 8-week group;therefore,the diabetic mice in the STZ 8-week group were selected for subsequent experiments.(2)Compared with the control group,mice in the STZ 8-week group and the STZ+SYN+AAV-GPR110 group exhibited a decrease in the retinal thickness and the number of retinal ganglion cells,those in the STZ+SYN group displayed a de-crease in the retinal thickness(all P＜0.05),and those in the other three groups presented a significant increase in the in-tensity of GFAP-positive expression and an increase in the level of IL-6,IL-1β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values(all P＜0.05).Compared with the STZ 8-week group,the retinal thickness and the number of retinal ganglion cells in the STZ+SYN group increased,the intensity of GFAP-positive expression decreased,and the level of IL-6,IL-1 β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values decreased(all P＜0.05).Compared with the STZ+SYN group,mice in the STZ+SYN+AAV-GPR110 group showed a decrease in the retinal thickness and the number of retinal ganglion cells,a significant increase in the intensity of GFAP-positive expression,and an increase in the level of IL-6,IL-1 β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values(all P＜0.05).Conclusion The GPR110 ligand could alleviate retinal neuroinflammation in diabetic mice by inhibiting the JAK2/STAT3 signaling pathway.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective To investigate the effect of a G-protein receptor 110(GPR110)ligand on retinal neuroinflam-mation in diabetic mice by regulating the Janus kinase 2/signal transduction and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods This experiment was divided into two parts.(1)Twelve C57BL/6J mice(24 eyes)were randomly divided into the control group,4-week streptozotocin(STZ)induction(STZ4-week)group,STZ 8-week group,and STZ 12-week group,with 3 mice in each group.The diabetic model was induced by intraperitoneal injection of STZ(150 mg·kg-1)in all groups except the control group.The expression of GPR110 and glutamine synthetase(GS)in the retinal tissue of mice was detected by immunofluorescence staining to screen the optimal acting time.(2)Thirty-two C57BL/6J mice(64 eyes)were divided into the control group,STZ 8-week group,the STZ+N-docosahexaenol ethanola-mine(SYN)group,and the STZ+SYN+adeno-associated virus-mediated GPR110(AAV-GPR110)group,with 8 mice in each group,and they were subjected to corresponding treatment.Immunohistochemistry was performed to detect the ex-pression of glial fibrillary acidic protein(GFAP)in mouse retinal tissues.ELISA was performed to detect the level of inter-leukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in mouse retinal tissues.Western blot was performed to detect the ratio of JAK2 to phosphorylated JAK2(p-JAK2)and that of STAT3 to phosphorylated STAT3(p-STAT3).Results(1)GPR110 in the retina of mice in the STZ 4-week group,STZ 8-week group,and STZ 12-week group was mainly expressed in Müller cells.The highest expression intensity of GPR110 was observed in the retina of mice in the STZ 8-week group;therefore,the diabetic mice in the STZ 8-week group were selected for subsequent experiments.(2)Compared with the control group,mice in the STZ 8-week group and the STZ+SYN+AAV-GPR110 group exhibited a decrease in the retinal thickness and the number of retinal ganglion cells,those in the STZ+SYN group displayed a de-crease in the retinal thickness(all P＜0.05),and those in the other three groups presented a significant increase in the in-tensity of GFAP-positive expression and an increase in the level of IL-6,IL-1β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values(all P＜0.05).Compared with the STZ 8-week group,the retinal thickness and the number of retinal ganglion cells in the STZ+SYN group increased,the intensity of GFAP-positive expression decreased,and the level of IL-6,IL-1 β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values decreased(all P＜0.05).Compared with the STZ+SYN group,mice in the STZ+SYN+AAV-GPR110 group showed a decrease in the retinal thickness and the number of retinal ganglion cells,a significant increase in the intensity of GFAP-positive expression,and an increase in the level of IL-6,IL-1 β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values(all P＜0.05).Conclusion The GPR110 ligand could alleviate retinal neuroinflammation in diabetic mice by inhibiting the JAK2/STAT3 signaling pathway.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

AIM To investigate the effects of Huazhuo Jiedu Shugan Formula(HJSGF)on improving learning and memory impairment in a rat model of vascular dementia(VD)via SIRT1/PGC-1α/PPARγ pathway.METHODS The SD rats were randomly divided into the sham control group,the model group,the donepezil group(0.5 mg/kg),and the low-,medium-and high-dose HJSGF groups(2.7,5.4,10.8 g/kg),with 10 rats in each group.The VD rat models established by bilateral common carotid artery permanent ligation(2-VO)had their neurological behavior assessment using the Longa5-point scale,and their modeling success confirmed by the Morris water maze test and their 3-week corresponding dosing of drugs by gavage afterward.After the drug administration,the rats had their spatial memory ability tested through behavioral experiments;their serum levels of IL-18 and IL-1β measured by ELISA;their histopathological changes and neuronal morphology in the hippocampal CA1 region observed by HE staining and Nissl staining;and their hippocampal protein expressions of SIRT1,PGC-1α and PPARγ detected by immunohistochemistry and Western blot.RESULTS Compared with the sham control group,the model group showed prolonged escape latency(P＜0.01);decreased platform crossing times and target quadrant residence time(P＜0.01);disorganized arrangement of hippocampal CA1 neurons,nuclear condensation,reduced Nissl bodies,increased secretion and protein expressions of IL-1β and IL-18(P＜0.01);and reduced hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.01).Compared with the model group,the groups intervened with donepezil or HJSGF showed shortened escape latency(P＜0.05,P＜0.01);increased platform crossing times and target quadrant residence time(P＜0.05,P＜0.01);alleviated damage of the hippocampal CA1 region,reduced secretion and protein expressions of IL-1β and IL-18(P＜0.05,P＜0.01);and elevated hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.05,P＜0.01).CONCLUSION HJSGF may alleviate the inflammatory responses in VD rats and therefore improve their learning and memory impairment by activating the SIRT1/PGC-1α/PPARγ signaling pathway.