Severe pneumonia is one of the most common and critical respiratory diseases in clinical practice. It is characterized by rapid progression， difficult treatment， high mortality， and many complications， posing a significant threat to the life and health of patients. The pathogenesis of severe pneumonia is highly complex， and studies have shown that its occurrence and development are closely related to multiple signaling pathways. Currently， the treatment of severe pneumonia mainly focuses on anti-infection， mechanical ventilation， and glucocorticoids， but clinical outcomes are often not ideal. Therefore， finding safe and effective alternative therapies is particularly important. In recent years， with the deepening of research into traditional Chinese medicine （TCM）， it has gained widespread attention in the treatment of severe pneumonia. This paper reviewed the relationship between severe pneumonia and relevant signaling pathways in recent years and how TCM regulated these pathways in the treatment of severe pneumonia. It was found that TCM could regulate the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， NOD-like receptor protein 3 （NLRP3）， and nuclear factor E₂-related factor 2 （Nrf2） signaling pathways， playing a role in reducing the inflammatory response， inhibiting cell apoptosis and pyroptosis， improving oxidative stress， and other effects in the treatment of severe pneumonia. Among these pathways， it was found that all of them regulated inflammation to treat severe pneumonia. Therefore， reducing inflammation is the core mechanism by which Chinese medicine treats severe pneumonia. This review provides direction for the clinical treatment of severe pneumonia and offers a scientific basis for the research and development of new drugs.

The rupture of carotid vulnerable plaques is the core pathological basis for major cardiovascular and cerebrovascular events. However， the insufficient alignment between existing animal models and the clinical disease and syndrome characteristics of traditional Chinese and western medicine has limited research progress. In this study， biomedical databases in China and abroad were systematically searched， and the modeling mechanisms and evaluation systems of carotid vulnerable plaque animal models were systematically assessed based on diagnostic criteria of both traditional Chinese and western medicine. Analysis of the clinical correspondence indicated that existing animal models can be categorized into four types： simple high-fat diet， surgical induction combined with high-fat feeding， genetic engineering combined with high-fat feeding， and drug induction combined with high-fat feeding. Among these， the compound strategy of surgical induction combined with high-fat feeding has become the current mainstream approach， showing good concordance with western medicine. The study found that the double balloon injury rabbit model and the ApoE^-/- mouse carotid artery tandem constriction combined with high-fat feeding model demonstrated a high degree of clinical correspondence with both traditional Chinese and western medicine in terms of vulnerable plaque imaging and pathological features. Nevertheless， existing models still face significant technical limitations in faithfully simulating plaque pathology and in translating findings to clinical applications. To address these challenges， integrating complex comorbidity mechanism construction， multimodal dynamic mechanism monitoring， and collaborative evaluation systems of traditional Chinese and western medicine could enable the development of highly concordant carotid vulnerable plaque disease-syndrome combination animal models. Such models would provide a reproducible experimental platform for targeted drug development to regulate plaque stability and for individualized precision treatment， as well as a theoretical basis for innovation in clinical diagnostic and therapeutic strategies.

Objective To compare the effect of serratus anterior plane block(SAPB)and thoracic para-vertebral block(TPVB)on acute and chronic pain and plasma tumor necrosis factor-α(TNF-α)level after breast cancer modified radical operation.Methods A total of 99 patients with elective breast cancer modified radical operation,aged 35-70 years,American Society of Anesthesiologists physical status(ASA):grade Ⅰ-11,Body Mass Index(BMI):18-25 kg/m2,were randomly divided into three groups:the simple patient-con-trolled intravenous analgesia(PCIA)group(C group),PCIA combined with TPVB group(TC group)and PCI A combined witj SAPB group(SC group).TPVB and SAPB were performed before induction in the TC group and the SC group,and the relevant situation of regional blocking operation was recorded.The Visual Analogue Scales(VAS)scores in rest and activity at 2,4,8,12,24,48 h after operation,effective pressing times of analgesic pump and remedial analgesia situation after operation were recorded.The TNF-α levels be-fore anesthesia and at postoperative 12,48 h,in postoperative 3,6 months were measured by enzyme linked immunosorbent assay(ELISA).Results Compared with the TC group,the block operation time in the SC group was shorter(P＜0.05).Compared with the C group,the VAS scores in the state of rest and activity at postoperative 2,4,8,12,24 h in the TC group and SC group were significantly decreased(P＜0.05),and the dosage of remifentanil during operation,incidence rates of postoperative nausea and vomiting,effective press-ing times of analgesic pump and rate of remedial analgesia were all decreased(P＜0.05).There was no statis-tical difference in the incidence rate of post-mastectomy pain syndrome(PMPS)among the three groups(P＞0.05).Compared with the C group,the levels of plasma TNF-α in the TC group and SC group were decreased at postoperative 12,48 h,in postoperative 3,6 months,moreover the VAS score in the patients with PMPS was lower(P＜0.05).Compared with the patients without PMPS occurrence,the levels of plasma TNF-α in postoperative 3,6 months in the patients with PMPS were significantly up-regulated(P＜0.05).Conclusion By blocking the afference of pain signals caused by peripheral injury and reducing plasma TNF-α level,SAPB or TPVB may relieve the acute and chronic pain degree in the patients with breast cancer modified radi-cal operation.

Objective To compare the value of the 2018 Chinese guideline prognostic score with that of the 2019 European Society of Cardiology(ESC)in the predicting efficiency for acute pulmonary embolism(APE)in 30-day all-cause mortality.Methods The data of the hospitalized patients with confirmed APE from January 2015 to December 2019 were retrospectively collected.According to death within 30 days,the patients were divided into a death group and a survival group.Subgroup analysis was performed according to gender,oxygen saturation and infection.The SPSS software was used to establish the receiver operating characteristic curve(ROC)for the two scores and calculated the area under the curve(AUC).The Delong's test was applied to compare the AUC differences.The net reclassification index(NRI)and integrated discrimination improvement(IDI)were calculated using the R software packages of survival,survIDINRI,and PredictABEL.Results 626 APE patients were enrolled,and 30-day death was predicted in those patients using two scores.In terms of overall discrimination,the 2018 Chinese guideline prognostic score was better than the 2019 ESC guideline prognostic score,with an AUC of 0.782 and 0.749,respectively;but there were no statistical differences between the two AUC(P＞0.05).In terms of prediction accuracy,the NRI of the 2019 ESC guideline prognostic score was 44.4%(95%CI:0.091～0.753),higher than that of the 2018 Chinese guidelines prognostic score,which increased by 58.6%(95%CI:0.161～0.917)in the correct reclassification to death group,while decreased by 14.2%(95%CI:-0.249～0.08)in the correct reclassification to survival group.IDI increased by 3.38%(P＜0.05).Subgroup analysis showed the prognostic scores of the 2018 Chinese guidelines and the 2019 ESC guidelines prognostic scores had predictive ability for patients with different gender and different oxygen saturation(P＜0.05),and the prognostic scores for co-infected population(AUC:0.749,0.772)(P＞0.05),non-coinfected population(AUC:0.652,0.833).Conclusions Both the 2018 Chinese guideline prognostic score and the 2019 ESC guideline prognostic score can predict 30-day mortality in APE patients,and have a better predictive ability for the co-infected population.However,the predictive accuracy of the former is higher than that of the latter in the survival group,and the score is more rapid and convenient for clinical application,while the latter has improved the prediction ability in the death group.

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

Objective To collect the clinical data of patients and construct a nomogram model to predict the prognosis of patients with humeral fracture treated with limited contact dynamic compression plate(LC-DCP).Methods A total of 372 patients with humeral fractures who received LC-DCP in our hospital from January 2013 to December 2020 weree randomly divided into a modeling cohort(n=260)and a validation cohort(n=112)according to 7∶3.Logistic regression model was used to analyze the data of the modeling cohort,and a Nomogram model was established according to the results of the influencing factors of poor prognosis of LC-DCP treatment for patients with humerus fractures.Nomogram was validated internally(modeling cohort)and externally(validation cohort)using calibration curve and ROC curve.Results The incidence of poor prognosis was 20.43％(76/372)in 372 patients with humeral fracture treated with LC-DCP.Univariate analysis showed that the age,incision length,intraoperative blood loss,time to start functional exercise and postoperative complications in the good prognosis group were significantly lower than those in the poor prognosis group(P＜0.05).Multivariate Logistic regression analysis showed that age ≥60 years old,incision length ≥5 cm,intraoperative blood loss ≥110 ml,start time of functional exercise ≥7 days after surgery,and postoperative complications were independent risk factors for the efficacy of LC-DCP in the treatment of proximal humeral fracture(P＜0.05).The calibration curve and ROC curve of the Nomogram model showed that the slope of the calibration curve for internal verification and external verification was close to 1,and the area under ROC for internal verification and external verification was 0.823 and 0.839 respectively.Conclusion The Nomogram model established in this study based on postoperative complications,intraoperative blood loss,age,postoperative functional exercise start time and incision length is effective and discriminative.

Objective:To investigate the role of CD8 + T cells in lethal Plasmodium yoelii 17XL ( Py 17XL) infection. Methods:BALB/c mice and C57BL/6 mice were infected with Py 17XL-infected red blood cells (1×10 6 cells/0.1 ml) through intraperitoneal injection to establish the mouse models of Py 17XL infection. Parasitemia (the percentage of erythrocytes infected with Py 17XL) and the survival rates of the mice was observed dynamically. Flow cytometry was used to detect the number of effector T cells (T EFF) and central memory T cells (T CM) of CD8 + T cell subpopulations, the expression of IFN-γ and granzyme B (GB) levels, and the expression of surface chemokine receptors CXCR3, CXCR6 and CX3CR1. FTY720 blocking experiment was conducted on Py 17XL-infected C57BL/6 mice to analyze the impact of CD8 + T cell migration on Py 17XL infection. Results:The parasitemia of BALB/c mice increased rapidly 5 d after infection and reached the peak on 8 d [(79.57±3.82)%]. Besides, the parasitemia was higher in BALB/c mice than in C57BL/6 mice 5-8 d after infection ( P<0.000 1). All BALB/c mice died on 9 d. The parasitemia of C57BL/6 mice reached the peak on 14 d [(48.19±3.19)%] and then decreased to 0 on 26 d. There was statistically significant difference in the survival rate between the two groups ( P<0.000 1). Flow cytometry results showed that compared with the BALB/c mice, the absolute number of CD8 + T cells in spleen and liver tissues and the number of CD8 + T EFF and CD8 + T CM cells in spleen and lymph nodes of C57BL/6 mice increased significantly ( P<0.05). Compared with the BALB/c mice, the levels of GB, IFN-γ and chemokines expressed by CD8 + T cells in spleen and liver tissues of C57BL/6 mice increased significantly ( P<0.05). The FTY720 blocking experiment showed that the survival rate, the absolute number of CD8 + T cells in liver and spleen, and the number of CD8 + CXCR3 + T cells decreased significantly in the experimental group ( P<0.05). Conclusions:CD8 + T EFF and CD8 + T CM cells contribute to resistance against Py 17XL infection by secreting GB and IFN-γ. The chemokine receptor CXCR3 plays an important role in mediating the chemotaxis of CD8 + T cells to spleen and liver.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.