ObjectiveTo observe the clinical efficacy of Tongfu Kuanzhong decoction （TFKZ） in the treatment of constipation-predominant irritable bowel syndrome （IBS-C） with spleen deficiency and Qi stagnation and its effects on anorectal manometry and colonic electrical activity parameters. MethodsSixty-four patients with IBS-C of the spleen deficiency and Qi stagnation type were included as research subjects and were randomized into the observation group （thirty-two cases） and control group （thirty-two cases）. The control group was orally administered mosapride citrate tablets， and the observation group was orally administered TFKZ. Both groups were treated for 4 weeks. The traditional Chinese medicine （TCM） syndrome scores， patient assessment of constipation symptoms （PAC-SYM） score， general anxiety disorder-7 （GAD-7） score， patient health questionnaire-9（PHQ-9）score， anorectal manometry， and colonic electrical activity parameters were observed before and after treatment in the two groups. ResultsThe total points of TCM syndromes were significantly lower in both groups after treatment （P<0.01） and lower in the observation group （P<0.05）. The fecal symptoms， rectal symptoms， abdominal symptoms， and total symptom scores of the patients in both groups were significantly decreased after treatment （P<0.01）， and the rectal symptoms， abdominal symptoms， and total symptom scores of the observation group were lower （P<0.05，P<0.01）. In both groups， the forced anal residual pressure and the initial rectal sensation threshold decreased after treatment （P<0.05，P<0.01）， and forced anal residual pressure in the control group was lower （P<0.01）. After treatment， the GAD-7 and PHQ-9 scores of patients in both groups decreased significantly （P<0.01）， and the GAD-7 score of the observation group was significantly lower （P<0.01）. After treatment， the average wave amplitude at different time points of each lead increased significantly in both groups， compared with that before treatment （P<0.01）. The average wave amplitude of each lead of the ascending colon， descending colon， sigmoid colon， and rectum in the observation group at 5 min before the meal and 10 min after the meal， as well as that of the ascending colon and rectum at 20 min and 30 min after the meal， was higher than that of the control group （P<0.05）. ConclusionTFKZ is effective in the treatment of IBS-C. Its mechanism may be related to the regulation of colonic function by down-regulating the forced anal residual pressure and the initial rectal sensation threshold and up-regulating the amplitude and frequency of intestinal electrical activity in each intestinal segment of the colon.

Objective To establish a HPLC method for determining thimerosal compounds in eye drops. Methods A gradient HPLC system was used in the quantitative analysis of thimerosal compounds on Shiseido MGII C₁₈ column （4.6 mm×250 mm，5 μm）, using 1% triethylamine solution （pH adjusted to 3.0 with phosphate） as mobile phase A, the methanol as mobile phase B, gradient elution, The column temperature was 40 ℃, the detection wavelength was 222 nm, the flow rate was 1 ml/min and the injection volume was 20 µl. Results The established method had good linearity within the concentration range of 4.3-216.7 μg/ml （r>0.999） for thimerosal, with average recoveries was 102.1%, RSD2.7%. Conclusion This method was simple, accurate and highly specific, and could be used for determination of thimerosal compound in eye drops.

OBJECTIVE To evaluate the efficacy and safety of letermovir in preventing cytomegalovirus （CMV） infection after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. METHODS A retrospective cohort study was conducted， enrolling patients who underwent allo-HSCT at the Department of Hematology， Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine， from August 30， 2022， to February 21， 2024. Patients who initiated letermovir prophylaxis within 28 days post-transplantation were assigned to the experimental group （99 cases）， while those who did not initiate letermovir within this period were assigned to the control group （18 cases）. The incidence and clinical characteristics of CMV infection （including the number of wangranran@xinhuamed.com.cn CMV infection cases， the number of cases progressing to CMV disease， recurrent CMV disease， onset time of CMV infection， and treatment duration）， immune function recovery within 120 days post-transplantation， and the occurrence of transplantation-related complications （including CD4+ and CD8+ T-cell recovery， Epstein-Barr virus infection， acute graft-versus-host disease， human herpesvirus 6 infection， and posttransplant lymphoproliferative disorders） and adverse events were recorded. Univariate and multivariate Cox regression analyses were performed to identify factors influencing CMV infection. RESULTS A total of 117 patients were included， among whom 15 developed CMV infection， 5 progressed to CMV disease， and 2 experienced recurrent CMV disease. The CMV infection rate in the experimental group was significantly lower than that in the control group （P＜0.001）， and the onset time of CMV infection was significantly delayed （P＝0.014）. The proportion of patients with CD4+ T-cell counts ≥200 cells/μL in the experimental group was significantly lower than that in the control group （P＝0.022）. During the follow-up period， elevated creatinine levels were observed in 1 patient， and nausea and vomiting were observed in 2 patients. Multivariate Cox regression analysis revealed that the use of high-dose corticosteroids was a risk factor for CMV infection （HR＝6.230， 95%CI of 1.255-30.926， P＝0.025）， while initiating letermovir within 28 days post-transplantation was a protective factor （HR＝0.125， 95%CI of 0.045-0.348， P＜0.001）. CONCLUSIONS Early initiation of letermovir after allo-HSCT significantly reduces the CMV infection rate and delays the onset of infection， with favorable short-term safety.

Objective To explore the mechanism of miR-421 affecting the occurrence and development of depression.Methods A depressive rat model was established by single intraperitoneal injection of lipopolysaccharide(LPS),and depressive behavior was detected by glucose preference test and open-field test.miRNA microarray chips and RT-PCR were used to analyze the expression level of miR-421 in hippocampus of the depressed rats.TargetScan database and mi RDB database were used to predict the target genes of miR-421.Dual luciferase reporter gene assay was used to observe the binding of miR-421 to the target genes.The impact of over-expression and inhibition of miR-421 on target genes was observed,then the influence of over-expression and inhibition of target genes on downstream factors was observed,and the related mechanism of miR-421 on depression was explored.Results miRNA microarray chips and RT-PCR assay showed that miR-421 was highly expressed in the hippocampus of the depressed rats(P<0.001),Inhibition of miR-421 expression could significantly restore the body weight and exercise ability of the depressed rats(P<0.001).Binding targets of Menin and miR-421 were predicted by TargetScan database,and interaction between Menin and miR-421 was demonstrated by dual-luciferase reporter gene assay.Menin expression was down-regulated while miR-421 was overexpressed(P<0.001),whereas it was up-regulated as miR-421 was inhibited(P<0.001).qPCR indicated that expressions of Caspase-3 and NF-κB in the hippocampus of the depressed rats was significantly increased(P<0.001),and IL-1β expression in the hippo-campus was significantly increased(P<0.01).When the expression of Menin was inhibited,the expressions of Caspase-3,NF-κB and IL-1β were increased(P<0.001),while the expressions of Caspase-3,NF-κB and IL-1β were decreased when Menin was overexpressed(P<0.001).Conclusions Inhibition of miR-421 expression can increase Menin expression,decrease Caspase-3 content,and reduce neuroinflammatory response,thereby improving depressive symptoms.

Objective To evaluate the efficacy of Huachansu tablets combined with transarterial chemoembolization(TACE)for treatment of primary hepatocellular carcinoma(HCC)and prognostic influence factors.Methods One hundred and eight patients with HCC were recruited according to the inclusion and exclusion criteria.Patients were randomly divided into treatment group and control group.The treatment group was treated with Huachansu tablets combined with TACE,and the control group was treated with TACE alone,with overall survival time(OS)and progression-free survival time(PFS)as the evaluation indexes.The COX regression analysis was used to evaluate the survival and prognostic effects and their influence factors in both groups.Results A total of 108 HCC patients were enrolled.The OS was 13.5 months in treatment group and 9.2 months in control group;the PFS was 6.8 months in treatment group and 5.3 months in control group,and the differences were significant statistically(all P<0.05).Multivariate COX regression analysis showed that Child-Pugh grade and cirrhosis were the independent risk factors for PFS in HCC patients.Child-Pugh grade were the independent risk factors for OS in HCC patients.ALBI is a protective factor for OS in HCC patients.Conclusions The treatment of HCC by Huachansu tablets combined with TACE can delay the progression of HCC and prolong PFS and OS of the patients with HCC.Child-Pugh grade,cirrhosis status,and ALBI were important factors affecting the prognosis of the patients with HCC.

Objective:To establish a nomogram model for predicting the risk of sepsis in diabetic foot patients, and to provide reference for clinical prevention and treatment.Methods:The clinical data of 430 patients with diabetic foot who were hospitalized in Chu Hsien-I Memorial Hospital of Tianjin Medical University from January 2022 to March 2023 were reviewed and collected, including age, gender, past medical history, smoking and drinking history, family history, diabetes course, Texas grade of diabetic foot and laboratory indicators within 24 hours after admission. Patients were divided into sepsis group and non-sepsis group according to the presence or absence of sepsis during hospitalization. The differences in clinical data between the two groups were compared. Multivariate Logistic regression analysis was used to screen the influencing factors of sepsis in patients with diabetic foot during hospitalization, and a nomogram predictive model was established. The performance of the prediction model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve and decision curve analysis (DCA). Internal validation was performed by using Bootstrap method.Results:A total of 430 patients were enrolled, among which 90 patients developed sepsis during hospitalization and 340 patients did not. There were statistically significant differences in diabetes course, Texas grade of diabetic foot, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), neutrophil to lymphocyte ratio (NLR), hemoglobin (Hb), albumin (Alb), glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and blood urea nitrogen (BUN) between the two groups. Multivariate Logistic regression analysis showed that diabetes course [odds ratio ( OR) = 2.774, 95% confidence interval (95% CI) was 1.053-7.308, P = 0.039], Texas grade of diabetic foot ( OR = 2.312, 95% CI was 1.014-5.273, P = 0.046), WBC ( OR = 1.160, 95% CI was 1.042-1.291, P = 0.007), HbA1c ( OR = 1.510, 95% CI was 1.278-1.784, P < 0.001), CRP ( OR = 1.007, 95% CI was 1.000-1.014, P = 0.036) were independent risk factors for sepsis in patients with diabetic foot during hospitalization, while Alb was a protective factor ( OR = 0.885, 95% CI was 0.805-0.972, P = 0.011). A nomogram predictive model was constructed based on the above 6 indicators. The ROC curve showed that the area under ROC curve (AUC) of the nomogram predictive model for identifying the sepsis patients was 0.919 (95% CI was 0.889-0.948). The AUC of the nomogram predictive model after internal verification was 0.918 (95% CI was 0.887-0.946). Hosmer-Lemeshow test showed χ2 = 2.978, P = 0.936, indicating that the calibration degree of the predictive model was good. Calibration curve showed that the predicted probability of sepsis was in good agreement with the actual probability. DCA curve showed that the nomogram predictive model had good clinical usefulness. Conclusion:The nomogram predictive model based on the risk factors of diabetes course, Texas grade of diabetic foot, WBC, HbA1c, CRP and Alb has good predictive value for the occurrence of sepsis in patients with diabetic foot during hospitalization, which is helpful for clinical screening of the possibility of diabetic foot patients progressing to sepsis, and timely personalized intervention for different patients.

Objective:To evaluate the effect of ultrasound-guided adductor canal block with bupivacaine liposome on analgesia in elderly patients undergoing total knee arthroplasty.Methods:This was a prospective study. Sixty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 65-83 yr, weighing 50-80 kg, scheduled for elective unilateral total knee arthroplasty under subarachnoid anesthesia from April 2023 to January 2024 in Zhengzhou Orthopaedic Hospital, were divided into 2 groups ( n=30 each) using a random number table method: bupivacaine liposome group (LB group) and ropivacaine group (R group). Ultrasound-guided adductor canal block was performed at 30 min before subarachnoid anesthesia, bupivacaine liposome diluent 20 ml (133 mg) was injected in LB group, and 0.5% ropivacaine 20 ml was injected in R group. Patient-controlled intravenous analgesia was performed after operation, and tramadol was used for rescue analgesia when the visual analogue scale (VAS) score ≥3. VAS scores at rest and during activity were recorded at 8, 12, 24, 48 and 72 h after surgery. The time to the first pressing analgesia pump and rescue analgesia were recorded within 72 h after surgery. The quadriceps muscle strength was measured at 1 day before surgery and 12, 24, 48 and 72 h after surgery. The knee joint range of motion was assessed at 1 day before surgery and 24, 48 and 72 h after surgery. Patient′s satisfaction with analgesia was recorded at 72 h after surgery. The adverse reactions within 72 h after surgery were also recorded. Results:Compared with R group, VAS scores at rest and during activity were significantly decreased at 12, 24, 48 and 72 h after surgery, the time to the first pressing analgesia pump was prolonged, the rate of rescue analgesia after surgery was decreased, the score for the patient′s satisfaction with analgesia was increased, the knee joint range of motion was increased ( P<0.05), and no significant change was found in the quadriceps muscle strength and incidence of adverse reactions in LB group ( P>0.05). Conclusions:Ultrasound-guided adductor canal block with bupivacaine liposome provides better analgesia than ropivacaine in elderly patients undergoing total knee arthroplasty.

Background: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. Objective: This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. Methods: Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. Results: Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. Conclusions GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.

Rearranged during transfection (RET) fusions are found in 0.7% to 2% of non-small cell lung cancer (NSCLC). Fusions between RET gene and other domains represent the distinct biological and clinicopathological subtypes of NSCLC. Recent years have witnessed the remarkable advancement of RET fusion-positive advanced NSCLC therapy. Conventional chemotherapy produced moderate clinical benefits. Prior to the introduction of targeted therapy or in the context of unavailability, platinum-based systemic regimens are initial therapy options. Immunotherapy predicted minimal response in the presence of RET fusions while currently available data have been scarce, and the single-agent immunotherapy or in combination with chemotherapy regimens are not recommended as initial systemic therapy in this population. The repurpose of multi-target kinase inhibitors in patients with RET fusion-positive NSCLC showed encouraging therapeutic activity, with only cabozantinib and vandetanib being recommended as initial or subsequent options under certain circumstances. However, there are still unmet clinical needs. Pralsetinib and selpercatinib have been developed as tyrosine kinase inhibitors (TKI) selectively targeting RET variation of fusions or mutations, and both agents significantly improved the prognosis of patients with RET fusion-positive NSCLC. Pralsetinib and selpercatinib have been established as preferred first-line therapy or subsequent therapy options. As observed with other TKIs treatment, resistance has also been associated with RET targeted inhibition, and the acquired resistance eventually affect the long-term therapeutic effectiveness, leading to limited subsequent treatment options. Therefore, it is essential to identify resistance mechanisms to TKI in RET fusion-positive advanced NSCLC to help reveal and establish new strategies to overcome resistance. Here, we review the advances in the treatment of RET fusion-positive advanced NSCLC.
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Carcinoma, Non-Small-Cell Lung/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-ret/genetics*

AIM: To observe the effects of Tangshen formula (TSF) treatment on lipid efflux and uptake in sodium palmitate (PA) induced RAW264.7 macrophages. METHODS: After 200 μmol/L PA induced RAW264.7 macrophages, TSF and PGC-1α-siRNA were given to intervene respectively. The lipid content in the cells was detected by ELISA kit; intracellular lipid droplet deposition was detected by BODIPY 493/503 and Filipin staining. Western blot and Real-time PCR were used to detect the expression of PGC-1α, LXR, ABCA1 and CD36. RESULTS: TSF diminished the levels of TC, TG and intracellular lipid droplet deposition in PA-induced RAW264.7 macrophages. Western blot and Real-time PCR analysis showed that TSF could up-regulate the expression of PGC-1α, LXR, ABCA1 and down-regulate the expression of CD36. Furthermore, silencing PCG-1α by SiRNA significantly suppressed the effects of upregulating the expression of PGC-1α, LXR and ABCA1, and downregulating the CD36 expression with TSF treatment. CONCLUSION: TSF may extenuate intracellular lipid droplet deposition in macrophages by upregulating cholesterol efflux through activating the PGC-1α/LXR/ABCA1 pathway and inhibiting lipid uptake through down-regulateing the expression of CD36.