ObjectiveTo observe the clinical efficacy of Shentong Zhuyutang combined with Dilongtang in the treatment of lumbar disc herniation （LDH） with Qi stagnation and blood stasis syndrome， and its effect on nucleus pulposus reabsorption and immune-inflammatory factors， exploring its therapeutic mechanism from the perspective of reabsorption. MethodsA total of 120 patients with LDH from the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine， treated between June 2020 and January 2023， were randomly divided into the control group （52 cases， with 8 dropouts） and the observation group （49 cases， with 11 dropouts） according to a random number table. The control group received routine treatment， while the observation group was treated with Shentong Zhuyutang combined with Dilongtang in addition to routine treatment. Visual Analogue Scale （VAS）， Oswestry Disability Index （ODI）， Japanese Orthopaedic Association （JOA） score， and traditional Chinese medicine （TCM） syndrome score were measured before treatment and after 3 courses of treatment. Venous blood samples were collected for the determination of serological indexes. MR examination was performed during the 6-month follow-up to calculate the absorption rate. ResultsAfter treatment， both groups showed significant reductions in VAS， ODI， TCM syndrome score， serum tumor necrosis factor （TNF）-α， matrix metalloproteinase （MMP）-9， and vascular endothelial growth factor （VEGF） levels， and a significant increase in JOA score compared with pre-treatment values （P<0.05）. Compared with the control group， the observation group showed significantly lower VAS， ODI， TCM syndrome score， serum TNF-α， MMP-9， and VEGF levels， and a significantly higher JOA score （P<0.05）. The proportion of nucleus pulposus reabsorption in the observation group was 57.14% （28/49）， significantly higher than 21.15% （11/52） in the control group （χ²=6.161， P<0.05）. ConclusionShentong Zhuyutang combined with Dilongtang can effectively relieve pain， improve lumbar function， and alleviate TCM clinical symptoms in LDH patients with Qi stagnation and blood stasis syndrome. Imaging findings suggest that the treatment promotes the reabsorption of nucleus pulposus protrusion， while laboratory testing shows reduced serum levels of TNF-α， MMP-9， and VEGF， which contribute to the rehabilitation of patients.

Adaptive immune cells play an important role in tumor immunity.The function of T cells in tumor microenviron-ment has been studied in detail,but B cells needs to be further explored.Due to the different characteristics of producing antibodies,secreting cytokines,and presenting antigens,tumor-infiltrating B cells are divided into two phenotypes:promoting and inhibiting tu-mor proliferation.This study reviews the specific functions of B cells in the tumor microenvironment in order to explore the mechanisms of B cells involved in tumor immunity,which may provide a basis for the precision treatment targeting B cells in tumor.

Objective To evaluate the efficacy and safety of amoxicillin-clavulanate(10∶1)for injection in the treatment of community-acquired pneumonia(CAP)in adult patients.Methods Eligible patients were randomized to receive amoxicillin-clavulanate(10∶1)2.2 g or ampicillin-sulbactam(2∶1)3.0 g via intravenous infusion q12h or q8h for 7 to 14 days.The primary endpoint was to the clinical efficacy 7-14 days after discontinuation of treatment.The secondary endpoints included microbiological efficacy and safety.Results All enrolled patients(n=324)were included in the full analysis set(FAS),specifically 165 patients receiving amoxicillin sodium-clavulanate potassium(10∶1)and 159 patients receiving ampicillin sodium-sulbactam sodium(2∶1).The clinical cure rate was 78.8％(130/165)for amoxicillin-clavulanate(10∶1)and 77.4％(123/159)for ampicillin-sulbactam 7-14 days after end of treatment(P＞0.05).The clinical cure rate was 87.5％(126/144)for amoxicillin-clavulanate(10∶1)and 87.4％(111/127)for ampicillin-sulbactam(2∶1)in per protocol set(P＞0.05).Therefore,amoxicillin-clavulanate(10∶1)was non-inferior to ampicillin-sulbactam in the primary endpoint in the treatment of CAP in adult patients.The overall bacterial eradication rate was 94.4％(34/36)for amoxicillin-clavulanate(10∶1)and 89.3％(25/28)for ampicillin-sulbactam(P＞0.05).The common study drug-related clinical adverse event were abnormalities of hepatic function in both the amoxicillin-clavulanate(10∶1)group(4.8％,8/165)and ampicillin-sulbactam group(3.1％,5/159)(P＞0.05).Conclusions Amoxicillin-clavulanate(10∶1)2.2 g Ⅳ infusion q12h or q8h for 7-14 days was noninferior to ampicillin-sulbactam in terms of clinical and microbiological efficacy in the treatment of CAP in adult patients.The safety of the two dosing regimens was comparable.

Objective To evaluate the efficacy and safety of amoxicillin-clavulanate(10∶1)for injection in the treatment of community-acquired pneumonia(CAP)in adult patients.Methods Eligible patients were randomized to receive amoxicillin-clavulanate(10∶1)2.2 g or ampicillin-sulbactam(2∶1)3.0 g via intravenous infusion q12h or q8h for 7 to 14 days.The primary endpoint was to the clinical efficacy 7-14 days after discontinuation of treatment.The secondary endpoints included microbiological efficacy and safety.Results All enrolled patients(n=324)were included in the full analysis set(FAS),specifically 165 patients receiving amoxicillin sodium-clavulanate potassium(10∶1)and 159 patients receiving ampicillin sodium-sulbactam sodium(2∶1).The clinical cure rate was 78.8％(130/165)for amoxicillin-clavulanate(10∶1)and 77.4％(123/159)for ampicillin-sulbactam 7-14 days after end of treatment(P＞0.05).The clinical cure rate was 87.5％(126/144)for amoxicillin-clavulanate(10∶1)and 87.4％(111/127)for ampicillin-sulbactam(2∶1)in per protocol set(P＞0.05).Therefore,amoxicillin-clavulanate(10∶1)was non-inferior to ampicillin-sulbactam in the primary endpoint in the treatment of CAP in adult patients.The overall bacterial eradication rate was 94.4％(34/36)for amoxicillin-clavulanate(10∶1)and 89.3％(25/28)for ampicillin-sulbactam(P＞0.05).The common study drug-related clinical adverse event were abnormalities of hepatic function in both the amoxicillin-clavulanate(10∶1)group(4.8％,8/165)and ampicillin-sulbactam group(3.1％,5/159)(P＞0.05).Conclusions Amoxicillin-clavulanate(10∶1)2.2 g Ⅳ infusion q12h or q8h for 7-14 days was noninferior to ampicillin-sulbactam in terms of clinical and microbiological efficacy in the treatment of CAP in adult patients.The safety of the two dosing regimens was comparable.

[Objective]To investigate the changes of intestinal flora in children with food allergy and constipation by high-throughput sequencing,and to analyze the function of intestinal flora,to provide a basis for the prevention and treatment of food allergy and constipation in children.[Methods]Totally 33 children with food allergy and constipation in Longgang District of Shenzhen were selected as the disease group(CPFA group),another 59 healthy children of the same age were recruited as the HC group.Stool samples were collected and subjected to high-throughput sequencing of 16SrRNA genes,followed by bioinformatics analysis.[Results]① The species abundance of HC group was higher than that of CPFA group,and the diversity of intestinal microbial community was different between the two groups;② At the phylum level,the relative abundance of Bacteroidota,Desulfobacterota in CPFA group was lower than that in HC group,and the relative abundance of Firmicutes,Actinobacteria and Proteobacteria in CPFA group was higher than that in HC Group(P<0.05);③ At the genus level,the relative abundance of Bacteroids,Parabacteroides in the CPFA group was lower than that in the HC group,and the relative abundance of Bifidobacterium,Escherichia-Shigella and Veillonella in the CPFA group was higher than that in the HC group;④ Functional analysis showed that there were significant differences in functional genes between the two groups.Compared with those in the HC group,the abundance of functional genes in valine,leucine and isoleucine biosynthesis,cysteine and methionine metabolism,fatty acid metabolism and Staphylococcus aureus infection were significantly increased in the CPFA group(P<0.05).The abundance of functional pathways related to bile acid biosynthesis and retinol metabolism was significantly decreased(P<0.05).[Conclusion]There are differences in intestinal flora and function between children with CPFA and HC,which may help to explore the pathogenesis of food allergy and constipation,and provide a theoretical basis for new therapeutic interventions.

Adaptive immune cells play an important role in tumor immunity.The function of T cells in tumor microenviron-ment has been studied in detail,but B cells needs to be further explored.Due to the different characteristics of producing antibodies,secreting cytokines,and presenting antigens,tumor-infiltrating B cells are divided into two phenotypes:promoting and inhibiting tu-mor proliferation.This study reviews the specific functions of B cells in the tumor microenvironment in order to explore the mechanisms of B cells involved in tumor immunity,which may provide a basis for the precision treatment targeting B cells in tumor.

BACKGROUND:Synovitis plays a leading role in the early progression of knee osteoarthritis and is a potential early therapeutic target.However,the mechanism of synovitis remains unclear.In animal models,increased systemic iron and intracellular iron uptake can induce and exacerbate osteoarthritis,but the association with ferroptosis in synovitis remains unclear.Further studies are needed to investigate the role of ferroptosis in the development and progression of synovitis in osteoarthritis. OBJECTIVE:To investigate the role of ferroptosis mediated by glutathione peroxidase 4(GPX4)in the development of synovitis in knee osteoarthritis. METHODS:The synovial tissues of 43 patients with osteoarthritis who underwent arthroscopic or joint replacement surgery and 10 patients undergoing arthroscopic treatment of meniscal injury or ligament tear were collected and divided into three groups according to the Kellgren-Lawrence grading of X-ray images:normal control group(KLG 0,n=10),early knee osteoarthritis group(KLG 1,2,n=20)and late knee osteoarthritis group(KLG 3,4,n=23).Hematoxylin-eosin staining was used to observe the severity of synovitis in each group,and iron deposition in the synovium in each group was evaluated by Prussian blue staining.The expressions of Acyl-CoA Synthetase Long Chain Family Member 4(ACSL4),GPX4,cyclooxygenase 2 and tumor necrosis factor α in the synovium were detected by immunohistochemical staining.Western blot and immunofluorescence were used to detect the expression of ferroptosis-related proteins ACSL4 and GPX4. RESULTS AND CONCLUSION:Compared with the normal control group,iron content in synovial tissue was increased in the knee osteoarthritis groups,and iron deposition in the late knee osteoarthritis group was higher than that in the early osteoarthritis group.ACSL4 was highly expressed in the synovial tissue of knee osteoarthritis compared with the normal control group(P＜0.01),and GPX4 was lowly expressed in the synovial tissue of knee osteoarthritis(P＜0.01).The expression level of ACSL4 increased with the progression of osteoarthritis,while the expression level of GPX4 decreased with the progression of osteoarthritis.The expression of cyclooxygenase 2 in the synovium of osteoarthritis was significantly higher than that in the normal synovium,and the expression was the highest in the early stage of osteoarthritis,which was significantly different from that in the advanced stage of osteoarthritis(P＜0.01).The expression of tumor necrosis factor α in the synovium of osteoarthritis was significantly higher than that in the normal synovium,but there was no significant difference between early and late osteoarthritis groups(P＞0.05).To conclude,the deposition of iron exists in the synovial tissue of osteoarthritis and ferroptosis is involved in the occurrence and progression of synovitis in knee osteoarthritis.

Aim To investigate the effect of alfentanil on myocardial ischemia-reperfusion injury(MIRI)in rats and its regulatory mechanism on the sphingosine kinase 1(SphK1)/sphingosine-1-phosphate(S1P)signaling pathway dur-ing this process.Methods SPF grade SD male rats were randomly divided into sham surgery group,model group,positive drug group(compound salvia miltiorrhiza group),low dose alfentanil group,high dose alfentanil group,and high alfentanil+SphK1 agonist group(alfentanil+PMA group),with 20 rats in each group.Except the sham operation group,the MIRI model was reproduced by ligating the left anterior descending coronary artery and reperfusion.The activities of serum lactate dehydrogenase(LDH),creatine kinase(CK)and aspartate aminotransferase(AST)were detected by auto-matic biochemical analyzer;TTC was applied to detect the size of myocardial infarction in rats;HE staining was applied to observe the morphological characteristics of rat myocardial tissue;TUNEL staining was applied to detect myocardial cell ap-optosis in rats;ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),inter-leukin-1β(IL-1β),and S1P;kits were applied to detect content of malondialdehyde(MDA)and activity of superoxide dismutase(SOD)in myocardial tissue;Western blot was applied to detect the expression level of SphK1 protein in myocar-dial tissue.Results Compared with the sham surgery group,the pathological damage to the myocardial tissue of rats was severe in the model group,the activities of serum central muscle injury markers LDH,CK,and AST,myocardial in-farction area,myocardial cell apoptosis rate,the levels of TNF-α,IL-6,IL-1β,MDA,S1P and the expression of SphK1 protein all increased,the activity of SOD decreased(P＜0.05).Compared with the model group,the myocardial tissue damage of rats was reduced in the positive drug group and the low and high dose alfentanil groups,the activities of serum central muscle injury markers LDH,CK,and AST,myocardial infarction area,myocardial cell apoptosis rate,the levels of TNF-α,IL-6,IL-1β,MDA,S1P and the expression of SphK1 protein all decreased,the activity of SOD increased(P＜0.05).The SphK1 agonist was able to reverse the impact of high-dose alfentanil on the above indicators(P＜0.05).Conclusion Alfentanil has protective effect on MIRI rats,and its mechanism may be related to the inhibition of SphK1/S1P signaling pathway.

Objective:To analyze the clinical characteristics of patients with Vibrio vulnificus infection, share diagnosis and treatment experience, and establish a rapid diagnosis procedure for this disease. Methods:This study was a retrospective case series study. From January 2009 to November 2022, 11 patients with Vibrio vulnificus infection who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of Guangdong Provincial People's Hospital Affiliated to Southern Medical University. The gender, age, time of onset of illness, time of admission, time of diagnosis, route of infection, underlying diseases, affected limbs, clinical manifestations and signs on admission, white blood cell count, hemoglobin, platelet count, C-reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, procalcitonin, albumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and blood sodium levels on admission, culture results and metagenomic next-generation sequencing (mNGS) results of pathogenic bacteria and the Vibrio vulnificus drug susceptibility test results during hospitalization, treatment methods, length of hospital stay, and outcomes of all patients were recorded. Comparative analysis was conducted on the admission time and diagnosis time of patients with and without a history of exposure to seawater/marine products, as well as the fatality ratio and amputation of limbs/digits ratio of patients with and without early adequate antibiotic treatment. For the survived patients with hand involvement, the hand function was assessed using Brunnstrom staging at the last follow-up. Based on patients' clinical characteristics and treatment conditions, a rapid diagnosis procedure for Vibrio vulnificus infection was established. Results:There were 7 males and 4 females among the patients, aged (56±17) years. Most of the patients developed symptoms in summer and autumn. The admission time was 3.00 (1.00, 4.00) d after the onset of illness, and the diagnosis time was 4.00 (2.00, 8.00) d after the onset of illness. There were 7 and 4 patients with and without a history of contact with seawater/marine products, respectively, and the admission time of these two types of patients was similar ( P>0.05). The diagnosis time of patients with a history of contact with seawater/marine products was 2.00 (2.00, 5.00) d after the onset of illness, which was significantly shorter than 9.00 (4.25, 13.00) d after the onset of illness for patients without a history of contact with seawater/marine products ( Z=-2.01, P<0.05). Totally 10 patients had underlying diseases. The affected limbs were right-hand in 8 cases, left-hand in 1 case, and lower limb in 2 cases. On admission, a total of 9 patients had fever; 11 patients had pain at the infected site, and redness and swelling of the affected limb, and 9 patients each had ecchymosis/necrosis and blisters/blood blisters; 6 patients suffered from shock, and 2 patients developed multiple organ dysfunction syndrome. On admission, there were 8 patients with abnormal white blood cell count, hemoglobin, and albumin levels, 10 patients with abnormal CRP, procalcitonin, and NT-proBNP levels, 5 patients with abnormal creatinine and blood sodium levels, and fewer patients with abnormal platelet count, ALT, and AST levels. During hospitalization, 4 of the 11 wound tissue/exudation samples had positive pathogenic bacterial culture results, and the result reporting time was 5.00 (5.00, 5.00) d; 4 of the 9 blood specimens had positive pathogenic bacterial culture results, and the result reporting time was 3.50 (1.25, 5.00) d; the mNGS results of 7 wound tissue/exudation or blood samples were all positive, and the result reporting time was 1.00 (1.00, 2.00) d. The three strains of Vibrio vulnificus detected were sensitive to 10 commonly used clinical antibiotics, including ciprofloxacin, levofloxacin, and amikacin, etc. A total of 10 patients received surgical treatment, 4 of whom had amputation of limbs/digits; all patients received anti-infection treatment. The length of hospital stay of 11 patients was (26±11) d, of whom 9 patients were cured and 2 patients died. Compared with that of the 6 patients who did not receive early adequate antibiotic treatment, the 5 patients who received early adequate antibiotic treatment had no significant changes in the fatality ratio or amputation of limbs/digits ratio ( P>0.05). In 3 months to 2 years after surgery, the hand function of 8 patients was assessed, with results showing 4 cases of disabled hands, 2 cases of incompletely disabled hands, and 2 cases of recovered hands. When a patient had clinical symptoms of limb redness and swelling and a history of contact with seawater/marine products or a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection. Conclusions:Vibrio vulnificus infection occurs most frequently in summer and autumn, with clinical manifestations and laboratory test results showing obvious infection characteristics, and may be accompanied by damage to multiple organ functions. Both the fatality and disability ratios are high and have a great impact on the function of the affected limbs. Early diagnosis is difficult and treatment is easily delayed, but mNGS could facilitate rapid detection. For patients with red and swollen limbs accompanied by a history of contact with seawater/marine products or with a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection.

Objective:To explore whether the muscarinic acetylcholine receptor M1(M1 AChR)regulate the expression of ionotropic glutamate receptor AMP A type subunit 1(GluA1)and ionotropic glutamate receptor AMP A type subunit 2(GluA2),thus participating in the effects of plateau hypoxia on learning and memory in rats.Methods:Rats were randomly divided into normoxic group(Control),plateau hypoxia group(Hypoxia)and plateau hypoxia+TAK-071(an agonist of M1AChR)group.Morris water maze was utilized to detect the learning and memory ability of rats.Immunohistochemistry was utilized to determine the distribution and expression levels of M1 AChR,GluA1,and GluA2 in hippocampal CA1 and CA3 areas of rats.Western Blot was utilized to determine the expression levels of M1 AChR,GluA1,p-GluA1(Ser845),GluA2 and p-GluA2(Ser880)in hippocampus of rats.RT-qPCR was utilized to determine the mRNA expression levels of M1 AChR,GluA1,GluA2,ionotropic glutamate receptor NMDA type subunit 2A(NR2A),tau and amyloid β-protein(Aβ)in hippocampus of rats.Results:Plateau hypoxia could significantly increase the escape latency of rats in the spatial navigation test and shorten the stay time of rats in the target quadrant in the spatial probe test,while TAK-071 treatment could significantly improve the memory status of rats damaged by plateau hypoxia in the spatial probe test.There was a good correlation between the expression of GluA1,GluA2 and M1 AChR in CA1 and CA3 regions of hippocampus.In hippocampus,the expressions of GluA1 and GluA2 were synchro-nized with their corresponding phosphorylated proteins,and the correlativity between GluA1 and GluA2 and M1 AChR changed due to plateau hypoxia was reversed after TAK-071 treatment.TAK-071 could significantly reduce(P＜0.05)the expression levels of M1 AChR,GluA1,GluA2,NR2A,tau and Aβ mRNA increased due to plateau hypoxia.Conclusion:Activating M1 AChR can improve the memory impairment of rats caused by plateau hypoxia by regulating the expression of GluA1,GluA2 and their phosphorylated proteins.