ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos（FF） in the treatment of acute lung injury（ALI） by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week， and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide（LPS） solution by tracheal drip to establish an ALI model. After successful model establishment， the rats were randomly divided into the model group， the FF low-dose group（3.0 g·kg^-1）， the FF high-dose group（6.0 g·kg^-1）， and the dexamethasone group（5 mg·kg^-1）， with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution， and the blank group and the model group were gavaged with an equal amount of saline， treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin（HE） staining， wet/dry mass ratio（W/D） of the lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， combined with multivariate statistical analysis， the potential biomarkers of FF in treating ALI were screened by variable importance in the projection（VIP） value>1， P<0.05 from t-test， and log₂fold change（FC）>1 or log₂FC<-1. Kyoto Encyclopedia of Genes and Genomes（KEGG） database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate（S1P）， phosphatidylinositol 3-kinase（PI3K）， protein kinase B1（Akt1）， and phosphorylated Akt1（p-Akt1） were examined by Western bolt. The expression levels of interleukin（IL）-6， IL-1β， and tumor necrosis factor（TNF）-α in BALF were detected by enzyme-linked immunosorbent assay（ELISA）. ResultsCompared with the blank group， rats in the model group showed ALI pathological features such as alveolar lumen dilatation， interstitial hemorrhage and massive inflammatory cell infiltration， and the protein concentration in BALF and W/D of the lung tissues were significantly elevated（P<0.01）. Compared with the model group， the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats， and the protein concentration in BALF and W/D were significantly decreased（P<0.05）， and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways， including arginine biosynthesis， sphingomyelin metabolism， alanine， aspartate and glutamate metabolism， taurine and hypotaurine metabolism， α-linolenic acid metabolism， niacin and nicotinamide metabolism， and retinol metabolism. The results of Western bolt and ELISA showed that， compared with the blank group， the model group exhibited significantly elevated expression levels of S1P， PI3K， Akt1 and p-Akt1 proteins in the lung tissues， as well as increased expression levels of IL-6， IL-1β and TNF-α in BALF（P<0.01）. Compared with the model group， the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group（P<0.05， P<0.01）. ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism， and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.

BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

Objective:To explore the clinical effect on the treatment of radiation induced deep ulcers in the inguinal region with ipsilateral anterolateral thigh chimeric perforator flap.Methods:From March 2020 to March 2024, retrospective analysis of 8 patients with radiation induced deep ulcers in the inguinal region were treated with ipsilateral anterolateral thigh chimeric perforator flap in the Medical Centre of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University. All ulcers induced by radiation were caused by postoperative radiotherapy in the inguinal region, of which 4 were of vulvar or penile cancer, 2 of urinary tract tumour, 1 of inguinal protuberant dermatofibrosarcoma and 1 of myofibroblastic sarcoma in lower abdominal wall. The course of the radiation induced ulcer was 0.5-11.0 years, with an average of 2.9 years. The sizes of the ulcerative wound were 2.5 cm × 3.0 cm - 5.5 cm × 7.5 cm. Preoperative biopsies of the tissues around wound and pelvic CT scans were performed to preliminarily exclude a tumour recurrence or an ulcerative malignancy, as well as to confirm the depth of radiation ulcer. The wound size after debridement was 4.5 cm × 6.0 cm-13.5 cm × 19.0 cm, with a depth of 2.0-4.0 cm. An ipsilateral anterolateral thigh chimeric perforator flap was transferred to reconstruct the wound, after the wound edges were cleared from tumour through intraoperative frozen section examinations. The flaps were 5.5 cm × 7.0 cm - 14.0 cm × 20.0 cm in size, with the volumes of muscle flap at 7.0 cm × 4.0 cm × 3.0 cm - 14.0 cm × 7.0 cm × 3.0 cm. After having the deep defect at the base of wound filled with a muscle flap, the wound surface was covered by the flap. Four patients had direct suture of the donor sites and 4 received a thick skin graft of head or contralateral thigh grafting. Survival of the anterolateral thigh chimeric perforator flaps and the healing of donor sites were observed after surgery through scheduled postoperative follow-up by the visits of outpatient clinic and distant interviews via telephone, WeChat or the internet hospital.Results:One of the ipsilateral anterolateral thigh chimeric perforator flaps had venous occlusion within 24 hours after surgery. Emergency surgical exploration revealed that it was caused by a haematoma compression due to haemorrhage in the muscle flap. Further debridement, haemostasis and suture were performed, then the wound healed. The rest of 7 flaps all survived. All donor sites healed primarily. The postoperative follow-up lasted for 5-17 months with all of the 8 patients, at 8.4 months in average. Both the donor and recipient sites healed well without recurrence of radiation ulcer in the affected sites. The appearance and texture of the flaps were good, and there was no obvious functional impairment at the donor sites.Conclusion:The treatment of radiation induced deep ulcer in the inguinal region with an ipsilateral anterolateral thigh chimeric perforator flap has shown good results, without recurrence of ulcer after surgery. The appearance and texture of the affected sites are good, and there is no secondary functional impairment at the donor site.

[This corrects the article DOI: 10.1016/j.apsb.2021.10.012.].

Objective To systematically evaluate the safety and efficacy of Kangfuxin liquid combined with adenosine monophosphate in the treatment of paediatric herpetic stomatitis.Methods Randomised controlled trials(RCTs)of Kangfuxin liquid combined with adenosine monophosphate for the treatment of paediatric herpetic stomatitis were searched in various databases,and Meta-analysis was performed using RevMan 5.4 software.Results A total of 12 RCTs with a sample size of 1,094 cases were included.Meta-analysis showed that the combination of Kangfuxin liquid with adenosine monophosphate significantly increased[RR=1.21,95%CI(1.16,1.28),P<0.000 01]the overall clinical efficacy rate of paediatric herpetic stomatitis.Compared with the conventional antiviral treatment group with adenosine monophosphate,the incidence of adverse events was lower in the Kangfuxin liquid group[RR=0.26,95%CI(0.14,0.51),P<0.000 01].In addition,the Kangfuxin liquid group could effectively shorten the time for herpes disappearance(skin lesion healing),pain disappearance,fever reduction,salivation disappearance and recovery of diet(P<0.05),and had advantages in promoting the recovery of lymphocytes(CD3+,CD4+,CD8+,and CD4+/CD8+),serological levels(CRP,TNF-α,WBC,IL-10,VEGF,EGF,and IL-6)(P<0.05).Conclusion Kangfuxin liquid combined with adenosine monophosphate has the better efficacy and safety in the treatment of paediatric herpetic stomatitis,and has advantages in shortening the symptomatic recovery time and improving the indicators of lymphocyte and serological levels in paediatric herpetic stomatitis.

Thousands of variant gene sequences of SARS-CoV-2 have been emerged since the COVID-19 epidemic broke out in Dec.2019.Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),Delta(B.1.617.2)and Omicron(B.1.1.529)were the most representative variants.With the continuous emergence of new variants,the predomi-nant strain in the global pandemic as of Jan.2025 is the Omicron BA.2.86-derived mutant,JN.1.The effectiveness of drugs against Omicron variants remains a key research focus in the treatment of SARS-CoV-2 infections.The infectiousness and pathogenicity of the variants altered remarkably due to mutations in the genome on S protein of the mutant strains,and these emerging variants are more likely to evade immunity and were more infectious than the previous prevalent variants.During the process of combating with the constantly emerging novel variants,drugs showed various effects on treatment of diseases caused by different variants.New drugs and treatment coun-termeasures are constantly updated with the prevalence of various variants.The current status of research on pres-ent drugs for treatment of SARS-CoV-2 and the therapeutic effects on emerging variants are reviewed in the article so as to provide reference for prevention and treatment of the upcoming evolved variants.

Objective To investigate the nebulization characteristics of human interferon α1b for injection.To characterize and compare the delivery rate,total drug substance and the aerodynamic characteristics between the two types of nebulizer.Methods Connect two types of nebulizers with a breathing simulator,respectively,and simulate the breathing patterns of an infant and child.Measure the delivery rate,total delivered dose,and delivery uniformity.The aerodynamic properties of human interferon α1b for injection were evaluated by the next generation impactor(NGI).The content of human interferon α1b was quantified by double antibody sandwich ELISA.Results In the three batches of samples in infant mode,the delivery rate and total delivered dose determind by A nebulizer were 0.45,0.49,0.44 μg·min-1,3.06,3.21,3.81 μg,respectcively;and 0.12,0.14,0.16 μg·min-1,0.73,0.73,0.75 μg,respectcively by B nebulizer.In child mode,the delivery rate and total delivered doses determined by A nebulizer were 1.36,1.49,1.20 μg·min-1,7.44,7.17,and 6.54 μg,respectcively;and 0.37,0.36,0.43 μg·min-1,1.66,1.59,and 1.41 μg,respectcively by B nebulizer.In child and infant mode,the ten results of the total drug substance delivered determined by nebulizer A were both between 65%to 135%of the average.The FPD,FPF,MMAD,and GSD determined by A neublizer of three batch samples were 2.48,2.92,2.35 μg,59.0%,57.4%,59.1%,4.18,4.34,4.15 μm,1.94,1.98,2.01,respectively.The FPD,FPF,MMAD and GSD determined by B neublizer of three batches samples were 2.70,3.38,3.06 μg,67.6%,66.4%,66.3%,3.55,3.65,3.68 μm,2.03,2.04,2.06,respectively.Conclusions The data obtained in this research characterized the in vitro nebulization characteristics of human interferon α1b for injection and provided a theoretical basis and reference for in vitro study and clinical practice.The influence of different types of nebulizers on nebulization characteristics was evaluated as well.It is suggested that the quality standard of nebulizers be strictly formulated and the use of nebulizers be standardized.

Objective:To analyze the effects of shared decision-making in patients with type 2 diabetic mellitus.Methods:Databases including PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Datebase, COVIP and SinoMed, for randomized controlled trials (RCTs) on the application of shared decision-making in patients with type 2 diabetic mellitus from inception to July 22, 2023, used R Studio software for meta-analysis.Results:A total of 14 RCTs and 2 606 patients with type 2 diabetic mellitus were included. The results of meta-analysis showed that the shared decision-making can alleviate the decision-making conflict of type 2 diabetic mellitus patients ( MD=-3.18, 95% CI -5.36 to -0.99, P<0.05), improve the decision-making self-efficacy ( MD=5.82, 95% CI 2.34 to 9.30, P<0.05), medication compliance ( RR=1.08, 95% CI 1.01 to 1.16, P<0.05), and diabetes-related knowledge ( SMD=0.46, 95% CI 0.16 to 0.75, P<0.05), reduce BMI ( MD=-0.75, 95% CI-1.33 to -0.17, P<0.05) and the HbA1c level ( MD=-0.45, 95% CI -0.65 to -0.24, P<0.05) in the 3-month follow-up. Conclusions:The shared decision-making improves the self-management in patients with type 2 diabetic mellitus. However, the long-term effect and potential risks of this model still need to be further studied. It is suggested that the application of shared decision-making in type 2 diabetic mellitus patients should be optimized in the future, and research on the long-term effects and potential risks of this model should be increased.

Objective:To summarize the characteristics and management experience of pregnancy after bariatric surgery.Methods:A retrospective analysis was conducted on four pregnant patients who had undergone pre-pregnant bariatric surgery and delivered at the Department of Obstetrics and Gynecology, Beijing Tsinghua Changgung Hospital, from January 2021 to December 2023. The analysis included the type of bariatric surgery, the interval between bariatric surgery and pregnancy, pregnancy complications, and neonatal birth conditions. Descriptive statistical analysis was used.Results:Among the four patients, two were primiparas and two were multiparas. All patients were obese (body mass index≥27.5 kg/m2) before undergoing sleeve gastrectomy. Before the current pregnancy, three patients had a normal body mass index, while one patient remained obese (body mass index 30.5 kg/m2). The interval between bariatric surgery and pregnancy exceeded one year for three patients (14, 14, and 60 months, respectively), while one patient became pregnant 10 months after surgery. Three patients developed normocytic anemia in early pregnancy, with the lowest hemoglobin levels of 101 to 106 g/L. After nutritional guidance and medication, hemoglobin levels returned to normal before delivery. One patient experienced a threatened late miscarriage at 26 weeks of gestation, which was successfully managed with tocolytic therapy. One patient was diagnosed with gestational diabetes at 27 weeks of gestation and achieved satisfactory blood glucose control through dietary and exercise guidance. Oral glucose tolerance tests for all four patients showed low fasting blood glucose levels (3.8-4.5 mmol/L) and 2-hour postprandial blood glucose levels (3.5-6.1 mmol/L). All four patients delivered at term, with no cases of small for gestational age infants.Conclusions:Pregnancy after bariatric surgery is prone to maternal nutrient deficiencies and blood glucose fluctuations. Multidisciplinary collaborative management and individualized nutritional guidance are recommended to reduce the risk of related complications.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.