[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Objective To study the immune regulatory effect of total flavonoids from houttuynia cordata on herpes simplex keratitis(HSK)mice and preliminarily explore its mechanism.Methods A surgical blade to mark the"#"character on the corneal epithelial layer of Balb/c mice and inoculate with I type herpes simplex virus(HSV-1)was used to construct an HSK model.The successfully identified HSK mice were randomly divided into model group,low(75 mg/kg)and high-dose(300 mg/kg)total flavonoids from houttuynia cordata groups,and high-dose total flavonoids from houttuynia cordata+toll like receptor(TLR)2 agonist Pam3CSK4(0.3 mg/kg)group.A control group was also established with 12 mice in each group.During the modeling and administration period,the corneal lesions in mice were observed daily using a slit-lamp microscope and scored.After administration,HE staining was used to observe the pathological changes of the mouse cornea.ELISA was used to detect the levels of interferon-γ(INF-γ),interleukin-2(IL-2),IL-4,and IL-6 in mouse serum.Western blot was used to detect the protein expression levels of TLR2,myeloid differentiation factor 88(MyD88),nuclear factor-kappaB p65(NF-κB p65)and p-NF-κB p65 in mouse corneal tissue.Results Compared with the control group,the model group mice showed corneal edema,ulcers,and neovascularization,with severe corneal damage and a large number of inflammatory cell infiltration.The serum levels of INF-γ and IL-2 significantly decreased,while the levels of IL-4 and IL-6 significantly increased(P<0.01).The protein expression levels of TLR2 and MyD88 and protein ratios of p-NF-κB p65/NF-κB p65 in corneal tissue significantly increased(P<0.01).Compared with the model group,the low and high dose of total flavonoids from houttuynia cordata groups showed improved corneal injury,the corneal lesion score significantly dereased(P<0.01).The serum levels of INF-γ and IL-2 significantly increased,while the levels of IL-4 and IL-6 significantly decreased(P<0.01).The protein expression levels of TLR2 and MyD88 and protein ratios of p-NF-κB p65/NF-κB p65 in corneal tissue significantly decreased(P<0.01).However,the TLR2 agonist Pam3CSK4 partially reversed the improvement effects of total flavonoids from houttuynia cordata on keratitis and immune imbalance in HSK mice.Conclusion The total flavonoids of houttuynia cordata can effectively improve corneal damage,regulate immune response,and suppress inflammation levels in HSK mice.Its mechanism of action may be related to the regulation of TLR2/NF-κB signaling pathway.

Cognitive impairment is the main clinical manifestation of many nervous system diseases such as stroke,multiple sclerosis,and neurodegeneration,and neuroinflammation is one of the key mechanisms for the onset of cognitive disorders.Chemokines are a class of highly conserved small-molecule secretory proteins that bind to the corresponding chemokine receptors located on cell mem-brane,activating downstream signaling pathways and playing an important role in cell migration,proliferation,differentiation,and sur-vival.In the central nervous system,chemokines and their receptors are involved in immune response and can exert a certain regulatory effect on neuroinflammation.This article reviews the research advances in chemokines and their receptors in cognitive disorders,in or-der to provide new insights and targets for the early diagnosis and treatment of related diseases.

Objective To study the immune regulatory effect of total flavonoids from houttuynia cordata on herpes simplex keratitis(HSK)mice and preliminarily explore its mechanism.Methods A surgical blade to mark the"#"character on the corneal epithelial layer of Balb/c mice and inoculate with I type herpes simplex virus(HSV-1)was used to construct an HSK model.The successfully identified HSK mice were randomly divided into model group,low(75 mg/kg)and high-dose(300 mg/kg)total flavonoids from houttuynia cordata groups,and high-dose total flavonoids from houttuynia cordata+toll like receptor(TLR)2 agonist Pam3CSK4(0.3 mg/kg)group.A control group was also established with 12 mice in each group.During the modeling and administration period,the corneal lesions in mice were observed daily using a slit-lamp microscope and scored.After administration,HE staining was used to observe the pathological changes of the mouse cornea.ELISA was used to detect the levels of interferon-γ(INF-γ),interleukin-2(IL-2),IL-4,and IL-6 in mouse serum.Western blot was used to detect the protein expression levels of TLR2,myeloid differentiation factor 88(MyD88),nuclear factor-kappaB p65(NF-κB p65)and p-NF-κB p65 in mouse corneal tissue.Results Compared with the control group,the model group mice showed corneal edema,ulcers,and neovascularization,with severe corneal damage and a large number of inflammatory cell infiltration.The serum levels of INF-γ and IL-2 significantly decreased,while the levels of IL-4 and IL-6 significantly increased(P<0.01).The protein expression levels of TLR2 and MyD88 and protein ratios of p-NF-κB p65/NF-κB p65 in corneal tissue significantly increased(P<0.01).Compared with the model group,the low and high dose of total flavonoids from houttuynia cordata groups showed improved corneal injury,the corneal lesion score significantly dereased(P<0.01).The serum levels of INF-γ and IL-2 significantly increased,while the levels of IL-4 and IL-6 significantly decreased(P<0.01).The protein expression levels of TLR2 and MyD88 and protein ratios of p-NF-κB p65/NF-κB p65 in corneal tissue significantly decreased(P<0.01).However,the TLR2 agonist Pam3CSK4 partially reversed the improvement effects of total flavonoids from houttuynia cordata on keratitis and immune imbalance in HSK mice.Conclusion The total flavonoids of houttuynia cordata can effectively improve corneal damage,regulate immune response,and suppress inflammation levels in HSK mice.Its mechanism of action may be related to the regulation of TLR2/NF-κB signaling pathway.

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.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To investigate the distribution of HIV-1 genotypes and drug resistance characteristics among newly reported HIV-infected men who have sex with men in Yunnan Province, and to analyze the correlation between HIV-1 genotypes and concurrence with other sexually transmitted diseases (STDs) .Methods:A single-center cross-sectional study was conducted. A total of 79 newly reported HIV-infected men who have sex with men were collected from the Yunnan Provincial Hospital of Infectious Diseases from September 2020 to May 2021. Meanwhile, their blood and initial-stream urine samples were collected. Antibodies against Treponema pallidum or herpes simplex virus type 2 were detected in blood samples, while nucleic acid amplification tests were performed for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycoplasma genitalium in urine samples. Viral RNA was extracted from plasma samples, and the gag, env, and pol gene fragments were amplified by nested reverse transcription polymerase chain reaction for genotyping and drug resistance analysis. Differences between groups were analyzed using the chi-square test, and correlations between HIV-1 genotypes and concurrence with STDs were analyzed using logistic regression. Results:Totally, 72 samples were successfully genotyped, and 5 genotypes were identified, including CRF07_BC (43.06%, 31/72), CRF01_AE (33.33%, 24/72), URF (18.06%, 13/72), CRF55_01B (2.78%, 2/72), and CRF68_01B (2.78%, 2/72). The 13 cases of URF were classified into 3 recombination patterns, including 11 cases of CRF01_AE/CRF07_BC, 1 case of CRF08_BC/CRF07_BC, and 1 case of B/CRF07_BC. Drug resistance analysis was conducted for 36 cases according to the pol sequences, and the HIV drug resistance rate was 5.56% (2/36). The rate of concurrence with other STDs was 40.28% (29/72), and HIV infection mostly coexisted with syphilis (20.83%, 15/72), followed by herpes simplex virus type 2 infection (16.67%, 15/72), Mycoplasma genitalium infection (11.11%, 8/72), gonorrhea (5.56%, 4/72) and Chlamydia trachomatis infection (2.78%, 2/72). The rate of concurrence with two or more STDs was 12.50% (9/72). Logistic regression analysis showed that there was no significant correlation between HIV-1 genotypes and concurrence with different STDs (all P < 0.05) . Conclusions:The HIV-1 genotypes among men who have sex with men in Yunnan Province were complex, the drug resistance in HIV strains had reached a moderately epidemic level, and HIV-infected patients were often accompanied by other STDs. Thus, it is necessary to pay close attention to the change of HIV-1 genotypes and simultaneous screening and treatment of STDs in HIV-infected patients.

Objective:To investigate the distribution of HIV-1 genotypes and drug resistance characteristics among newly reported HIV-infected men who have sex with men in Yunnan Province, and to analyze the correlation between HIV-1 genotypes and concurrence with other sexually transmitted diseases (STDs) .Methods:A single-center cross-sectional study was conducted. A total of 79 newly reported HIV-infected men who have sex with men were collected from the Yunnan Provincial Hospital of Infectious Diseases from September 2020 to May 2021. Meanwhile, their blood and initial-stream urine samples were collected. Antibodies against Treponema pallidum or herpes simplex virus type 2 were detected in blood samples, while nucleic acid amplification tests were performed for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycoplasma genitalium in urine samples. Viral RNA was extracted from plasma samples, and the gag, env, and pol gene fragments were amplified by nested reverse transcription polymerase chain reaction for genotyping and drug resistance analysis. Differences between groups were analyzed using the chi-square test, and correlations between HIV-1 genotypes and concurrence with STDs were analyzed using logistic regression. Results:Totally, 72 samples were successfully genotyped, and 5 genotypes were identified, including CRF07_BC (43.06%, 31/72), CRF01_AE (33.33%, 24/72), URF (18.06%, 13/72), CRF55_01B (2.78%, 2/72), and CRF68_01B (2.78%, 2/72). The 13 cases of URF were classified into 3 recombination patterns, including 11 cases of CRF01_AE/CRF07_BC, 1 case of CRF08_BC/CRF07_BC, and 1 case of B/CRF07_BC. Drug resistance analysis was conducted for 36 cases according to the pol sequences, and the HIV drug resistance rate was 5.56% (2/36). The rate of concurrence with other STDs was 40.28% (29/72), and HIV infection mostly coexisted with syphilis (20.83%, 15/72), followed by herpes simplex virus type 2 infection (16.67%, 15/72), Mycoplasma genitalium infection (11.11%, 8/72), gonorrhea (5.56%, 4/72) and Chlamydia trachomatis infection (2.78%, 2/72). The rate of concurrence with two or more STDs was 12.50% (9/72). Logistic regression analysis showed that there was no significant correlation between HIV-1 genotypes and concurrence with different STDs (all P < 0.05) . Conclusions:The HIV-1 genotypes among men who have sex with men in Yunnan Province were complex, the drug resistance in HIV strains had reached a moderately epidemic level, and HIV-infected patients were often accompanied by other STDs. Thus, it is necessary to pay close attention to the change of HIV-1 genotypes and simultaneous screening and treatment of STDs in HIV-infected patients.

Objective:To explore the safety and effectiveness of the application of sevoflurane inhalation sedation and analgesia during dressing changes in children with extensive burns.Methods:A prospective randomized controlled research was conducted. From March 2020 to January 2023, 216 children with extensive burns who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Kunming Children's Hospital. According to the random number table, the children were divided into sevoflurane group and ibuprofen group, with 103 cases left in sevoflurane group (67 males and 36 females, aged 1 (1, 2) years), and 98 cases left in ibuprofen group (67 males and 31 females, aged 1 (1, 2) years) after the exclusion of several dropped-out children. Children in sevoflurane group received sevoflurane inhalation for sedation and analgesia during dressing changes, while those in ibuprofen group took oral ibuprofen for analgesia before dressing changes. The heart rate, mean arterial pressure (MAP), and percutaneous arterial oxygen saturation (SpO 2) of the children were monitored and recorded at 30 minutes before the start of dressing changes, immediately after debridement, and at 30 minutes after the completion of dressing changes. The face, legs, activity, cry, and consolability scale and Ramsay sedation scale were used to evaluate the pain intensity and degree of sedation, respectively, at 30 minutes before the start of dressing changes, immediately after debridement, and at 30 minutes after the completion of dressing changes. The duration of dressing changes and the total number of dressing changes during hospitalization were recorded. The Houston Pain Outcome Instrument questionnaire was used to assess the satisfaction of the dressing-changing surgeons and a family member of the child with the analgesic effects during the process of dressing change when the children were discharged from the hospital. The occurrence of adverse reactions such as respiratory depression and hypoxemia that occurred during the process of dressing change were monitored and recorded. Data were statistically analyzed with independent sample t test, analysis of variance for repeated measurement, Wilcoxon rank-sum test, chi-square test, and Fisher's exact probability test. Results:At 30 minutes before the start of dressing changes and 30 minutes after the completion of dressing changes, there were no statistically significant differences in heart rate, MAP, and SpO 2 between children in the two groups ( P>0.05). Immediately after debridement, compared with those in ibuprofen group, the heart rate and MAP of children in sevoflurane group were significantly decreased (with t values of 8.10 and 4.37, respectively, P<0.05), while the SpO 2 was significantly increased ( t=21.77, P<0.05). At 30 minutes before the start of dressing changes and 30 minutes after the completion of dressing changes, there were no statistically significant differences in the score of pain intensity and score of sedation degree between children in the two groups ( P>0.05). Immediately after debridement, compared with that in ibuprofen group, the score of pain intensity of children in sevoflurane group was significantly decreased, while the score of sedation degree was significantly increased (with t values of 42.87 and 72.45, respectively, P<0.05). The duration of dressing changes and the total number of dressing changes during hospitalization of patients in sevoflurane group were (18±3) min and (4.1±1.0) times, respectively, which were both significantly shorter than (26±7) min and less than (6.6±1.4) times in ibuprofen group, respectively (with t values of -4.44 and 14.17, respectively, P<0.05). Upon discharge, the satisfaction scores of dressing-changing surgeons and the family members of children with the analgesic effects during the process of dressing change in sevoflurane group were significantly higher than those in ibuprofen group (with t values of 44.23 and 36.55, respectively, P<0.05). There were no statistically significant differences in the incidence of respiratory depression, hypoxemia, hypotension, coughing, nausea, and vomiting during the process of dressing change between children in the two groups ( P>0.05). Conclusions:Application of sevoflurane inhalation during dressing changes in children with extensive burns can safely and effectively control pain and sedation, shorten the time for dressing change, with fewer adverse reactions. This method can be used for routine dressing change in pediatric burn wards.

Objective To explore the pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)and the mechanism of Traditional Chinese Medicine(TCM)-based prescription for"Bringing Blood Downward"targeting SONFH through the OPG/RANKL/RANK signaling pathway.Methods Fifty male SD rats were randomly divided into model group and control group.The rats in the model group were treated with LPS and methylprednisolone to build a SONFH model.After 6 weeks,two rats were randomly selected respectively from the two groups,and the SONFH model was confirmed by histomorphological examination under light microscopy.The rats in a low,medium and high dose treatment groups(group L,M,and H)were intragastrically administrated with the Prescription for"Bringing Blood Downward"at concentrations of 2.5/5/10 g/kg.While the rats in the model group and control group were intragastrically administrated with normal saline at a concentration of 5 g/(kg·d).The pathological changes and expression levels of OPG,TRAF-6,and RANKL in each group were examined 4 weeks later.Results Compared with the model group,chondrocytes and cell matrix of groups L,M and H were less reduced,osteoclastic absorption and trabecular structure were less destroyed and the cells were less adipose.The adipocyte density in the control group and each treatment group was significantly lower than that in the model group(P<0.01).In the control group,the bone marrow cavity area was smaller than that in the model group(P<0.05),but there was no significant difference between each dose treatment groups and the model group(P>0.05).The expression levels of OPG,RANKL,TRAF-6 and OPG/RANKL ratio in the control group and groups L,M and H were significantly lower than those in the control group(P<0.01).Conclusion The TCM-based prescription for"Bringing Blood Downward"works to treat SONFH byregulating the activity of osteoclasts and osteogenic differen-tiation process of osteoblasts,improving the microcirculation environment of the femoral head,and inducing the formation of trabecular bone through the OPG/RANKL/RANK signaling pathway.It functions with its multitargetsin diverse methods.