OBJECTIVE To investigate the role of clinical pharmacists in the individualized treatment of a rare case of diffuse pulmonary microabscesses caused by Streptococcus constellatus complicated with organizing pneumonia （OP） in a non-immunocompromised patient. METHODS For a middle-aged， non-immunocompromised patient with a one-year disease course， whose imaging findings showed the coexistence of diffuse microabscesses and OP caused by S. constellatus pulmonary abscess， the clinical pharmacist， based on pharmacokinetics/pharmacodynamics characteristics， assisted the physician in optimizing the previously ineffective anti-infective regimen to Ceftriaxone sodium for injection combined with Metronidazole and sodium chloride injection， so as to enhance coverage of mixed anaerobes and lesion penetration. After the patient’s hemoptysis ceased， the clinical pharmacist recommended timely initiation of low-dose Methylprednisolone sodium succinate for injection to manage OP. Upon discharge， sequential oral therapy with Linezolid tablets， Metronidazole tablets， Methylprednisolone tablets and Omeprazole enteric-coated tablets was prescribed. RESULTS After implementation of the individualized treatment regimen， the patient’s hemoptysis resolved， pulmonary lesions significantly regressed， and the patient was discharged in a stable condition. At the three-month follow-up， the patient remained stable. CONCLUSIONS For chronic persistent pulmonary infection complicated with OP in a non-immunocompromised host， clinical pharmacists assist clinicians in optimizing anti-infective regimens and recommend the timely initiation of anti-inflammatory therapy after infection control， thereby contributing to favorable clinical outcomes. Individualized treatment of such complex cases requires comprehensive consideration of pathogen coverage， pathological barriers， and the timing of anti-inflammatory intervention.

ObjectiveTo evaluate the larvicidal effect of ultrasonic waves against Aedes albopictus larvae at various exposure parameters (distance and time), and to preliminarily investigate the effects of different containers (water volume and depth) and ultrasonic devices on the larvicidal efficacy, so as to provide experimental evidence for the application of ultrasound-based mosquito control technology. MethodsUnder controlled laboratory conditions, two commercially available ultrasonic devices [40 kHz/300 W and (50±5) kHz/70 W] were used to systematically examine the effects of exposure distance (20, 40, 60, 80, and 100 cm), exposure duration (1, 3, 6, 15 and 60 min), larval instar(Ⅰ‒Ⅱ and Ⅲ‒Ⅳ）, and container type on the immediate mortality of Aedes albopictus larvae collected from urban areas of Shanghai. Statistical analysis of the mortality rates of larvae among different experimental groups was performed using the chi-square test. ResultsUltrasonic exposure exerted a detectable larvicidal effect against Aedes albopictus larvae of all instars. For early-instar larvae, exposure time significantly affected mortality at all tested distances (20, 40, 60, 80 and 100 cm), with χ² values ranging from 25.57 to 32.74 ( all P<0.001). No significant distance effect was observed in the first and second instar larvae after short-term exposure (1 and 3 min; P>0.05). However, a distance-dependent effect emerged from 6 min onward (P<0.05). During short-term exposure (1 min and 3 min) at close range (20 cm and 40 cm), the immediate mortality of the third and fourth instar larvae was higher than that of the first and second instar larvae. Conversely, during prolonged exposure (15 min and 60 min), the first and second instar larvae exhibited significantly higher mortality than that of the third and fourth instar larvae. These results indicated that larval mortality was jointly influenced by exposure duration and distance. Preliminary experiments indicated that larvicidal efficacy in shallow water was lower than that in deep water. No significant difference in larvicidal effect was observed between the two ultrasonic devices with different frequencies and power outputs. ConclusionUnder laboratory conditions, ultrasound can effectively kill Aedes albopictus larvae, and the larvicidal effect is jointly influenced by larval instar, exposure distance, and aquatic environment. Compact ultrasonic devices show potential for field application in biological mosquito control.

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

Objective:To investigate the role and mechanism of PM(2.5)exposure on airway inflammation in juvenile rats based on macrophage recruitment induced by JNK/CCl2 signaling pathway.Methods:A total of 50 juvenile SD rats were randomly divided into 5 groups(n=10).The control group received no treatment,the PM(2.5)group received PM(2.5)particulate matter expo-sure,and the PM(2.5)+Anisomycin group received PM(2.5)exposure and Anisomycin,an activator of JNK,intravenously.Rats in the PM(2.5)+SP600125 group received PM(2.5)exposure and intravenous administration of the JNK inhibitor SP600125,and rats in the PM(2.5)+Pirfenidone group received PM(2.5)exposure and intravenous administration of Pirfenidone,a CCl2 inhibitor.The rats were euthanized and lung tissue was harvested.JNK,phosphorylated JNK(p-JNK)and CCl2 protein expressions were detected by Western blot.Hematoxylin-eosin(HE)staining was used to detect the pathological changes of lung airway tissue and score the pulmo-nary bronchial inflammation.The number of macrophages in alveolar lavage fluid was analyzed by flow cytometry.The levels of IL-6,IL-1β,and TNF-α in alveolar lavage fluid were determined by ELISA.Results:The expression levels of JNK,p-JNK,and CCl2 among all groups(F=205.296,950.408,260.019;all P<0.001)and macrophage content(F=48.414;P<0.001),pulmonary bronchial inflammation score(F=101.703;P<0.001)and IL-6(H=44.890;P<0.001),IL-1β(H=42.071;P<0.001),TNF-α(F=297.154;P<0.001)were statistically significant.Compared with the control group,the expressions of JNK/CCl2 pathway proteins JNK,p-JNK,and CCl2 in PM(2.5)group were significantly up-regulated(all P<0.05),while the content of macrophages was increased(P<0.05),and the pulmonary and bronchial inflammation score was significantly increased(P<0.05).The levels of IL-6,IL-1β,and TNF-α were up-regulated(all P<0.05).Compared with PM(2.5)group,the content of macrophages in PM(2.5)+Anisomycin group was sig-nificantly increased(P<0.05),the pulmonary bronchial inflammation score was significantly increased(P<0.05),and the levels of IL-6,IL-1β,and TNF-α were increased(all P<0.05).The expression levels of JNK,p-JNK,and CCl2 were increased(all P<0.05).Compared with PM(2.5)group,the content of macrophages in PM(2.5)+SP600125 group and PM(2.5)+Pirfenidone group were signifi-cantly decreased(P<0.05),and the pulmonary bronchial inflammation score was significantly decreased(P<0.05).In addition,the levels of IL-6,IL-1β,and TNF-α were significantly decreased(all P<0.05).Compared with PM(2.5)group,the expression levels of JNK,p-JNK,and CCl2 in PM(2.5)+SP600125 group were down-regulated(all P<0.05),and the expression level of CCl2 in PM(2.5)+Pirfenidone group was down-regulated(all P<0.05).Conclusion:JNK/CCl2 pathway induces macrophage recruitment and pro-motes allergic airway inflammation induced by PM(2.5)particulate matter exposure in juvenile rats.

Objectives:To explore the imaging features of patients with isolated left ventricular apical hypoplasia(ILVAH). Methods:Twelve patients diagnosed with ILVAH(ILVAH group)in our hospital from April 2018 to August 2023 were enrolled,and all of them received transthoracic echocardiography(TTE)examination;9 patients underwent CMR examination;and 1 patient underwent CT examination.Clinical data and imaging characteristics of the patients were analyzed.At the same time,twelve healthy age and sex matched participants who underwent physical examination in the same period were selected as the control group. Results:TTE showed that:compared with the control group,the left ventricular transverse diameter([46.3±5.7]mm vs.[57.8±12.6]mm)and right ventricular long diameter([62.0±4.2]mm vs.[73.6±6.4]mm)were larger in the ILVAH group(P＜0.05),the left ventricular long diameter([63.0±3.5]mm vs.[53.4±8.2]mm)was smaller(P＜0.05).There was no significant difference in right ventricular transverse diameter between the two groups(P＞0.05).The interventricular septum was convex to the right ventricle,and the thickness at the apex was(5.2±2.0)mm in the ILVAH group.The papillary muscles were all attached to the flat left ventricular apex.Among the 9 patients who underwent CMR examination,adipose tissue replacement was found in the left ventricular apex in 7 out of the 9 patients,and endocardial fibrosis was found in 2 out of the 9 patients. Conclusions:The clinical presentation of ILVAH is non-specific,but there are specific imaging manifestations that may help improve the understanding of the disease.

The long-acting cabotegravir and rilpivirine injection regimen（CAB+RPV regimen）is the first approved long-acting antiretroviral therapy（ART）for HIV in China，administered once every two months. This regimen provides an innovative alternative to daily oral ART，benefiting virologically suppressed patients. Several large clinical-studies have shown that the CAB+RPV regimen achieves comparable virologic suppression and safety to daily oral regimens，while significantly enhancing patient satisfaction. Based on international and domestic HIV/AIDs guidelines and clinical evidence，this consensus offers expert recommendations on patient selection，clinical management，and key communication strategies for healthcare providers to support the effective use of this regimen，aiming to improve quality of life for people living with HIV and accumulate domestic clinical experience with this advanced treatment approach.

Objective:To investigate the effect of metformin on the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU) and its possible mechanism.Methods:Colon cancer cell lines HCT-116 and HT-29 were cultured in vitro, and the CCK-8 method was used to determine cell viability after intervention with different concentrations (1.25, 2.5, 5, 10, 20, 40, 80 mmol/L) of metformin hydrochloride (MET-HCl) or different concentrations (1.25, 2.5, 5, 10, 20, 40 μmol/L) of 5-FU. The survival rate and 48-hour half maximal inhibitory concentration ( IC50) of the two drugs were calculated. The combined index (CI) of MET-HCl and 5-FU was calculated using the Chou-Talalay model, and the concentrations of MET-HCl and 5-FU in subsequent experiments were determined based on the concentration of the two drugs when the inhibition rate (Fa) was 0.5. The CCK-8 method and Annexin V-FITC/PI flow cytometry were used to detect the survival rate and apoptosis rate of HCT-116 cells or HT-29 cells treated with the two drugs alone and in combination at experimental concentrations, respectively. Cells treated with drug free culture flnid were used as the control group. CXCR4 specific small interfering RNA (siRNA) was transfected into HCT-116 cells and HT-29 cells, and the decreased ( P < 0.05) expression of CXCR4 protein detected by Western blotting indicated successful knockdown of CXCR4. CCK-8 method was used to detect the survival rate of cells with CXCR4 knockdown by two drugs alone and in combination, and the untransfected cells added drug free culture fluid were served as the si-control group. Western blotting was used to detect the expression of proteins related to the CXCR4/Akt signaling pathway in HCT-116 cells or HT-29 cells treated with two drugs alone or in combination. Results:CCK-8 assay showed that MET-HCl and 5-FU decreased the viability of HCT-116 and HT-29 cells in a concentration-time-dependent manner; at 48 h, IC50 of MET-HCl and 5-FU in HCT-116 cells were (13.0±5.8) mmol/L and (16.9±7.2) μmol/L, respectively, and IC50 in HT-29 cells were (8.6±2.8) mmol/L and (9.7±3.1) μmol/L, respectively. When the cell inhibition rates of HCT-116 cells or HT-29 cells detected by CCK-8 method were 50%, 75% and 90% after 48 h of treatment, the corresponding CI values of HCT-116 cells were 0.48, 0.37 and 0.25, and HT-29 cells were 0.57, 0.51 and 0.49, suggesting that the combination of the two drugs had a synergistic effect. Based on Fa = 0.5, the experimental concentrations of MET-HCl and 5-FU were determined to be 10 mmol/L and 5 μmol/L. CCK-8 method showed that after HCT-116 cells or HT-29 cells were treated with 10 mmol/L MET-HCl, 5 μmol/L 5-FU alone or in combination for 48 h, the cell viability of each drug group was lower than that of the control group (all P < 0.05), there was no statistically significant difference in cell viability between MET-HCl alone and 5-FU alone (both P > 0.05), and the cell viability of the combination of the two drugs was lower than that of the two drugs alone (both P < 0.01). After CXCR4 was knocked down, the cell viability of each drug group was lower than that of the si-control group (all P < 0.05), but there was no significant difference in cell viability between the two drugs alone and the combination of the two drugs (all P > 0.05). Flow cytometry showed that after 24 h of treatment, the apoptosis rate of HCT-116 cells or HT-29 cells treated with MET-HCl alone or the combination of the two drugs was higher than that of the control group (all P < 0.05), but there was no statistically significant difference in the apoptosis rate of cells treated with 5-FU alone compared to the control group (all P > 0.05); the apoptosis rate of HCT-116 cells treated with the combination of the two drugs was higher than that of the two drugs alone (both P < 0.05); the apoptosis rate of HT-29 cells treated with the combination of the two drugs was higher than that of 5-FU alone ( P < 0.05), but there was no significant difference with MET-HCl alone ( P > 0.05). Western blotting showed that the relative expression levels of CXCR4, p-Akt and XRCC1 proteins in HCT-116 or HT-29 cells treated with MET-HCl alone and in combination of two drugs were lower than those in the control group (all P < 0.05), but there was no statistically significant difference in the relative expression levels of the 3 proteins in the two cell lines treated with 5-FU alone compared to the control group (all P > 0.05); the relative expression levels of the 3 proteins in the two cell lines treated with MET-HCl alone and in combination of two drugs were lower than those treated with 5-FU alone (all P < 0.05), the relative expression levels of CXCR4 and p-Akt proteins in the two cell lines treated with the combination of two drugs were lower than those treated with MET-HCl alone (all P < 0.05), and the relative expression level of XRCC1 protein in HCT-116 cells treated with the combination of two drugs was lower than that in HCT-116 cells treated with MET-HCl alone ( P < 0.05), but there was no significant difference in the relative expression level of XRCC1 protein in HT-29 cells treated with the combination of two drugs and MET-HCl alone ( P > 0.05). Conclusions:MET-HCl may reduce the expression of XRCC1 through the CXCR4/Akt signaling pathway, thereby enhancing the sensitivity of colon cancer cells to 5-FU.

Objective:To investigate the effect of metformin on the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU) and its possible mechanism.Methods:Colon cancer cell lines HCT-116 and HT-29 were cultured in vitro, and the CCK-8 method was used to determine cell viability after intervention with different concentrations (1.25, 2.5, 5, 10, 20, 40, 80 mmol/L) of metformin hydrochloride (MET-HCl) or different concentrations (1.25, 2.5, 5, 10, 20, 40 μmol/L) of 5-FU. The survival rate and 48-hour half maximal inhibitory concentration ( IC50) of the two drugs were calculated. The combined index (CI) of MET-HCl and 5-FU was calculated using the Chou-Talalay model, and the concentrations of MET-HCl and 5-FU in subsequent experiments were determined based on the concentration of the two drugs when the inhibition rate (Fa) was 0.5. The CCK-8 method and Annexin V-FITC/PI flow cytometry were used to detect the survival rate and apoptosis rate of HCT-116 cells or HT-29 cells treated with the two drugs alone and in combination at experimental concentrations, respectively. Cells treated with drug free culture flnid were used as the control group. CXCR4 specific small interfering RNA (siRNA) was transfected into HCT-116 cells and HT-29 cells, and the decreased ( P < 0.05) expression of CXCR4 protein detected by Western blotting indicated successful knockdown of CXCR4. CCK-8 method was used to detect the survival rate of cells with CXCR4 knockdown by two drugs alone and in combination, and the untransfected cells added drug free culture fluid were served as the si-control group. Western blotting was used to detect the expression of proteins related to the CXCR4/Akt signaling pathway in HCT-116 cells or HT-29 cells treated with two drugs alone or in combination. Results:CCK-8 assay showed that MET-HCl and 5-FU decreased the viability of HCT-116 and HT-29 cells in a concentration-time-dependent manner; at 48 h, IC50 of MET-HCl and 5-FU in HCT-116 cells were (13.0±5.8) mmol/L and (16.9±7.2) μmol/L, respectively, and IC50 in HT-29 cells were (8.6±2.8) mmol/L and (9.7±3.1) μmol/L, respectively. When the cell inhibition rates of HCT-116 cells or HT-29 cells detected by CCK-8 method were 50%, 75% and 90% after 48 h of treatment, the corresponding CI values of HCT-116 cells were 0.48, 0.37 and 0.25, and HT-29 cells were 0.57, 0.51 and 0.49, suggesting that the combination of the two drugs had a synergistic effect. Based on Fa = 0.5, the experimental concentrations of MET-HCl and 5-FU were determined to be 10 mmol/L and 5 μmol/L. CCK-8 method showed that after HCT-116 cells or HT-29 cells were treated with 10 mmol/L MET-HCl, 5 μmol/L 5-FU alone or in combination for 48 h, the cell viability of each drug group was lower than that of the control group (all P < 0.05), there was no statistically significant difference in cell viability between MET-HCl alone and 5-FU alone (both P > 0.05), and the cell viability of the combination of the two drugs was lower than that of the two drugs alone (both P < 0.01). After CXCR4 was knocked down, the cell viability of each drug group was lower than that of the si-control group (all P < 0.05), but there was no significant difference in cell viability between the two drugs alone and the combination of the two drugs (all P > 0.05). Flow cytometry showed that after 24 h of treatment, the apoptosis rate of HCT-116 cells or HT-29 cells treated with MET-HCl alone or the combination of the two drugs was higher than that of the control group (all P < 0.05), but there was no statistically significant difference in the apoptosis rate of cells treated with 5-FU alone compared to the control group (all P > 0.05); the apoptosis rate of HCT-116 cells treated with the combination of the two drugs was higher than that of the two drugs alone (both P < 0.05); the apoptosis rate of HT-29 cells treated with the combination of the two drugs was higher than that of 5-FU alone ( P < 0.05), but there was no significant difference with MET-HCl alone ( P > 0.05). Western blotting showed that the relative expression levels of CXCR4, p-Akt and XRCC1 proteins in HCT-116 or HT-29 cells treated with MET-HCl alone and in combination of two drugs were lower than those in the control group (all P < 0.05), but there was no statistically significant difference in the relative expression levels of the 3 proteins in the two cell lines treated with 5-FU alone compared to the control group (all P > 0.05); the relative expression levels of the 3 proteins in the two cell lines treated with MET-HCl alone and in combination of two drugs were lower than those treated with 5-FU alone (all P < 0.05), the relative expression levels of CXCR4 and p-Akt proteins in the two cell lines treated with the combination of two drugs were lower than those treated with MET-HCl alone (all P < 0.05), and the relative expression level of XRCC1 protein in HCT-116 cells treated with the combination of two drugs was lower than that in HCT-116 cells treated with MET-HCl alone ( P < 0.05), but there was no significant difference in the relative expression level of XRCC1 protein in HT-29 cells treated with the combination of two drugs and MET-HCl alone ( P > 0.05). Conclusions:MET-HCl may reduce the expression of XRCC1 through the CXCR4/Akt signaling pathway, thereby enhancing the sensitivity of colon cancer cells to 5-FU.

The long-acting cabotegravir and rilpivirine injection regimen（CAB+RPV regimen）is the first approved long-acting antiretroviral therapy（ART）for HIV in China，administered once every two months. This regimen provides an innovative alternative to daily oral ART，benefiting virologically suppressed patients. Several large clinical-studies have shown that the CAB+RPV regimen achieves comparable virologic suppression and safety to daily oral regimens，while significantly enhancing patient satisfaction. Based on international and domestic HIV/AIDs guidelines and clinical evidence，this consensus offers expert recommendations on patient selection，clinical management，and key communication strategies for healthcare providers to support the effective use of this regimen，aiming to improve quality of life for people living with HIV and accumulate domestic clinical experience with this advanced treatment approach.