OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

OBJECTIVE: Myocardial inflammation during myocardial infarction (MI) could be inhibited by regulating arachidonic acid (AA) metabolism. Recent studies demonstrated that Sini Decoction (SND) was identified to be an effective prescription for treating heart failure (HF) caused by MI. But the anti-inflammatory mechanism of SND remained unclear. The work was designed to investigate the anti-inflammatory mechanism of SND through the AA metabolism pathway in vitro and in vivo experiments. METHODS: An inflammatory injury model of H9c2 cells was established by lipopolysaccharide (LPS)-stimulated macrophage-conditioned medium (CM). The MI model was built by the ligation of left anterior descending (LAD) branch of coronary artery in rat. Meanwhile, the rats were divided into five groups: sham group, MI group, MI + Celecoxib group, MI + low-dose SND group (SND-L) and MI + high-dose SND group (SND-H). Cardiac function, histopathological changes and serum cytokines were examined four weeks later. Western blot analysis was conducted to verify the key enzymes levels in the AA metabolic pathway, including phospholipase A2 (PLA2), cyclooxygenases (COXs) and lipoxygenases (LOXs). RESULTS: These in vivo results demonstrated that SND could improve the cardiac function and pathological changes of rats with MI, and regulate the key inflammatory molecules in the AA metabolism pathway, including sPLA2, COX-1, COX-2, 5-LOX and 15-LOX. In vitro, SND could decrease the release of pro-inflammatory cytokines including TNF-α and IL-6 and inhibit cell apoptosis in CM-induced H9c2 cells. Moreover, SND could protect H9c2 cells from the damage of CM by regulating nuclear factor kappa-B (NF-κB) signal pathway and the expression of COX-2. CONCLUSION SND may be a drug candidate for anti-inflammatory treatment during MI by regulating the multiple targets in the AA metabolism pathway.

Colorectal cancer is a common clinical malignant tumor. As the main therapeutic method of colorectal cancer, radiotherapy has a good inhibitory effect on tumor progression. In recent years, because of its good physical and biological advantages, carbon ion has shown better clinical efficacy than traditional radiotherapy in the treatment of local recurrence or distant metastasis of colorectal cancer. In this article, basic and clinical studies related to the efficacy of carbon ion therapy for the recurrence of colorectal cancer in recent years were reviewed, aiming to provide theoretical basis for preventing and reducing adverse reactions after radiotherapy and prolonging the survival of colorectal cancer patients.

Objective:To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism.Meth-ods:In 60 SPF-grade male Kunming mice,10 mice were taken as blank group by random number table method,and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group[2.5×10-3 g/(kg·3 d)],Shenqi Yiliu decoction low[13.515 g/(kg·d)],me-dium[27.03 g/(kg·d-1)],and high dose[27.030 g/(kg·d)]combined with cisplatin group[2.5×10-3 g/(kg·3 d)],10 mice in each group were treated for 13 d.After 24 h of the last dose,the mice were anesthetized and sacrificed,and the tumor inhibition rate,spleen index and thymus index of each drug group were determined;HE staining was performed to observe the histopathological changes of tumor in mice;ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate;p-ERK1/2,C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot;ERK,C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR.Results:Compared with blank group,the average body mass and spleen index of mice in model group were decreased(P<0.05).Compared with model group,the tumor inhibition effect of each treatment group was obvious,and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way,im-proved the average body mass,spleen index and thymus index of mice,promoted the necrosis of tumor cells and increased the necrotic area.EGF and IFN-γ contents,P-ERK1/2,C-Myc,PD-L1 protein expressions and ERK,C-Myc,PD-L1 mRNA expression levels were decreased in tumor tissues(P<0.05).Compared with cisplatin group,the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant,and the difference was statistically significant(P<0.05).Conclusion:Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues,which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect.

Helicobacter pylori (Hp) is a unipolar, microaerobic, multiflagellar, spiral-shaped Gram-negative bacterium that survives and colonizes human gastric mucosa. As a classⅠcarcinogen associated with gastric cancer, long-term stimulation of gastric mucosa by Hp can cause atrophic gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. It has been reported that Hp can cause epithelial-mesenchymal transition (EMT) in gastric epithelial cells, thereby inducing gastric cancer. We review the mechanism of Hp-induced EMT in gastric epithelial cells, in order to provide new insights for early diagnosis and targeted therapy of gastric cancer.

Objective To investigate the clinical effects and pregnancy outcomes of using luteal phase long protocol and GnRH antagonist protocol in patients with polycystic ovary syndrome(PCOS)who have failed their first GnRH antagonist protocol therapy.Methods The clinical data of 163 PCOS patients who underwent IVF/ICSI-ET were retrieved.After the failure of their first GnRH antagonist protocol treatment,they were divided into two groups in the second controlled ovarian hyperstimulation(COH)cycle:Luteal phase long protocol group(n=95)and Gn-RH antagonist protocol group(n=68).A retrospective analysis and comparison of basic clinical data,clinical and laboratory indicators,and pregnancy outcomes between two groups were conducted.Results ① There was no sta-tistically significant difference in basic clinical indicators between two group except LH.② Compared the first and second cycle treatments of patients in the luteal phase long protocol group,the initiation dose of gonadotropin(Gn),total number of Gn days,total Gn usage,estradiol(E2)on the day of hCG injection,number of retrieved eggs,oocyte maturation rate,2PN fertilization rate,2PN cleavage rate,blastocyst formation rate,high-quality blas-tocyst formation rate,and moderate to severe OHSS rate were significantly higher than those in the first GnRH an-tagonist cycle(P＜0.05).The GnRH antagonist protocol group also showed similar improvements.③ The com-parison of the second COH cycle between two groups showed that the total number of Gn days,total Gn usage,and total Gn cost in the luteal phase long protocol group were significantly higher(P＜0.05),while the E2 and LH on the day of hCG injection,and the maturation rate of eggs were significantly lower than those in the GnRH antagonist protocol group(P＜0.05).However,there was no statistically significant difference in the number of retrieved eggs,2PN fertilization,2PN cleavage,blastocyst formation rate,high-quality blastocyst formation rate,and OHSS rate between the two groups;④ The comparison of fresh transplantation cycles for the second COH cycle between the two groups showed that the luteal phase long protocol fresh transplantation rate,implantation rate,clinical preg-nancy rate,and live birth rate were slightly higher than those of the GnRH antagonist protocol group,but the differ-ence was not statistically significant.Comparing the outcomes of pregnancy following the initial frozen-thawed em-bryo transfer(FET)between two groups,the biochemical pregnancy rate and clinical pregnancy rate of the GnRH antagonist protocol group were higher than those of the luteal phase long protocol group(P＜0.05).However,no significant statistical variations were found in implantation rate,live birth rate,neonatal gestational age,and birth weight.Conclusion For PCOS patients who fail the first GnRH antagonist protocol,an appropriate increase in the initiating dose and usage of Gn can achieve satisfactory pregnancy outcomes with both protocols.Compared with change to a luteal phase long protocol,reusing the GnRH antagonist protocol still maintains its long-standing advan-tages,such as shorter total Gn days,lower costs,and better patient compliance.

Tyrosol is a natural polyphenolic product that is widely used in chemical, pharmaceutical and food industries. Currently, the de novo synthesis of tyrosol by Escherichia coli suffers from issues such as low cell density and poor yield. Therefore, the phenylpyruvate decarboxylase mutant ARO10^F138L/D218G obtained in our previous study was fused with an alcohol dehydrogenase from different microorganisms for fusion expression, and the optimal ARO^{10F138L/D218G}-L-YahK produced 1.09 g/L tyrosol in shake flasks. In order to further improve tyrosol production, feaB, a key gene in the competing pathway of 4-hydroxyphenylacetic acid, was knocked out, and the resulted strain produced 1.26 g/L tyrosol with an increase of 21.15% compared to that of the control. To overcome the low cell density in tyrosol fermentation, the quorum-sensing circuit was used to dynamically regulate the tyrosol synthesis pathway, so as to alleviate the toxic effect of tyrosol on chassis cells and relieve the growth inhibition. Using this strategy, the yield of tyrosol was increased to 1.74 g/L, a 33.82% increase. In a 2 L fermenter, the production of tyrosol in the engineered strain TRFQ5 dynamically regulated by quorum-sensing reached 4.22 g/L with an OD₆₀₀ of 42.88. Compared with those in the engineered strain TRF5 statically regulated by induced expression, the yield was increased by 38.58% and the OD₆₀₀ was enhanced by 43.62%. The combination of blocking the competing pathway using gene knockout technology, and reducing the inhibitory effect of tyrosol toxicity on chassis cells through quorum-sensing dynamic regulation increased the production of tyrosol. This study may facilitate the biosynthesis of other chemicals with high toxicity.
Escherichia coli/genetics* ; Biological Products ; Bioreactors ; Fermentation

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To investigate the efficacy of Modified Banxia Xiexin Decoction on patients with functional dyspepsia (FD) and its impact on gastric function.Methods:From June 2021 to December 2022, at the Department of Gastroenterology, Wenzhou Central Hospital, a total of 56 patients with FD who met the diagnostic criteria of Rome Ⅳ were prospectively enrolled. The patients were treated with Modified Banxia Xiexin Decoction for 4 weeks. The clinical efficacy was evaluated by the upper gastrointestinal symptom severity index score. The gastric function was assessed by standard gastric loading test of liquid nutrient meal and standard gastric emptying test of solid meal. The total scores of dyspeptic symptoms, the maximal satiety threshold of proximal stomach, the initial satiety threshold of proximal stomach and 5-hour solid gastric emptying rate were compared before and after the treatment. During the treatment and in 4-week follow-up after treatment, the adverse events (such as nausea, diarrhea, dizziness and rash) were observed. Wilcoxon rank sum test and paired sample t-test were used for statistical analysis. Results:After the treatment, 14 FD patients were cured, 22 patients showed significant improvement, 12 patients had response, and 8 patients showed no improvement. The total efficacy rate was 85.71%(48/56). The total score of dyspepsia symptoms after the treatment was lower than that before treatment (3.00(1.00, 4.00) vs. 13.00(8.00, 18.00)), and the difference was statistically significant ( Z=-7.96, P<0.001). After the treatment, the maximal satiety threshold of proximal stomach and 5-hour solid gastric emptying rate were both higher than those before treatment ( (897.45±98.82) mL vs. (588.46±60.26) mL, (87.59±12.74)% vs. (36.59±15.95)%), and the differences were statistically significant ( t=19.98 and 18.70, both P<0.001). The initial satiety threshold of proximal stomach before and after treatment was compared((131.84±52.91) mL vs. (130.0±47.61) mL), and the difference was not statistically significant( P>0.05). No adverse events related to this study were observed during treatment period and in the 4-week follow-up. Conclusions:The Modified Banxia Xiexin Decoction can improve proximal gastric compliance and gastric emptying function in patients with FD. Additionally, it can alleviate dyspeptic symptoms and have good clinical efficacy and high safety.