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.

ObjectiveTo investigate the effects of berbamine hydrochloride on sorafenib resistance in hepatocellular carcinoma cells and the underlying mechanisms. MethodThe sorafenib-resistant cell line SMMC-7721/S was selected by the concentration increment method starting at 1.25 μmol·L^-1 sorafenib. Both SMMC-7721 and SMMC-7721/S cells were treated with 0， 2.5， 5， 10， 15， 20 μmol·L^-1 sorafenib， and the cell counting kit-8 （CCK-8） assay was employed to determine the half maximal inhibitory concentration （IC₅₀） and calculate the resistance index （RI）. Western blot was conducted to compare the expression of proteins involved in autophagy and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway between SMMC-7721 and SMMC-7721/S cells. Furthermore， SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 2.5， 5， 10 μmol·L^-1 sorafenib， and the cell growth was assessed by the CCK-8 assay. In addition， SMMC-7721 and SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 5 μmol·L^-1 sorafenib， and the cell proliferation was examined by the colony formation assay. The immunofluorescence assays with Microtubule-associated protein 1 light chain 3 （LC3） and LysoTracker as probes were employed to assess the lysosomal acidification in SMMC-7721 cells treated with 5 μmol·L^-1 berbamine hydrochloride or 0.1 μmol·L^-1 autophagy inhibitor bafilomycin A1 （Baf）. Further， the expression of proteins involved in autophagy and PI3K/Akt/mTOR signaling pathway was determined by Western blot and compared between groups. ResultSorafenib showed the IC₅₀ of 9.56 mol·L^-1 （P<0.01） and 7.99 mol·L^-1 for SMMC-7721/S and SMMC-7721 cells， respectively， at 24 h. The resistance index （RI） of SMMC-7721/S for sorafenib was 1.20 （P<0.01）， which indicated mild resistance. Compared with SMMC-7721 cells， SMMC-7721/S cells exhibited up-regulated expression of p-mTOR， p-Akt， and LC3Ⅱ， down-regulated expression of p62 protein （P<0.01）， and unchanged Akt protein level. CCK-8 and colony formation assays demonstrated that the combination of berbamine hydrochloride and sorafenib exhibited a synergistic effect （Q>1.15）， with berbamine hydrochloride partially reversing the resistance of liver cancer cells to sorafenib. The immunofluorescence detection of LC3 revealed that berbamine hydrochloride and Baf significantly increased LC3 in SMMC-7721 cells. The detection with LysoTracker as the probe showed that berbamine hydrochloride inhibited the acidity of lysosomes in SMMC-7721 cells （P<0.01）， indicating the suppression of autophagy. Berbamine hydrochloride further enhanced the downregulation of p-mTOR and p-Akt protein levels and did not change the Akt protein level in SMMC-7721 cells exposed to sorafenib. Berbamine hydrochloride inhibited the increase in p-mTOR expression， down-regulated the p-Akt protein level， and did not change the total Akt protein level in the SMMC-7721/S cells exposed to sorafenib. ConclusionBerbamine hydrochloride can ameliorate the resistance of liver cancer cells to sorafenib by inhibiting cellular autophagy and the PI3K/Akt/mTOR signaling pathway.

Objective: Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. Methods: We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. Results: The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. Conclusion The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.

Objective To explore the application effect of healthcare failure mode and effect analysis (HFMEA) in nursing risk management of emergency surgery for patients with traumatic brain injury (TBI). Methods Taking the HFMEA model as the theoretical framework, the emergency surgical process of TBI was analyzed, a flow chart was drawn, and the potential risk factors were analyzed. Corresponding intervention programs were adopted for high-risk failure modes, and 80 patients from November 2022 to April 2023 were conducted with routine management before implementation of HFMEA (control group), the other 80 patients from May to October 2023 were conducted with management after implementation of HFMEA (observation group). The surgical efficiency (preoperative waiting time, surgical preparation time, anesthesia induction time, postoperative handover time), the incidence rates of adverse events in the operation room (incomplete preparation of supplies, contamination of surgical drapes, insufficient or defective intraoperative instruments, errors in writing nursing records, incorrect or missing items in handover information), the incidence rates of perioperative complications (low intraoperative body temperature, pressure injury, abnormal fluctuations in vital signs during surgery, wound infection, lung infection) and satisfaction degree of surgical doctors to nurses for current operations (itinerant nurses, instrument nurses) were compared between two groups. Results The observation group had significantly shorter preoperative waiting time, surgical preparation time, anesthesia induction time, and postoperative handover time compared to the control group (P < 0.01). The incidence rate of adverse events in the operation room for the observation group was 16.25%, which was significantly lower than 46.25% of the control group (P < 0.01). The incidence rate of complications was 8.75% in the observation group, which was significantly lower than 26.25% in the control group (P < 0.01). Satisfaction degree of the doctors to nurses for the current operation in the observation group was significantly higher than that in the control group (P < 0.05). Conclusion Application of the HFMEA model in the perioperative nursing management of patients with emergency surgery for TBI can effectively improve surgical efficiency, reduce the incidence rates of nursing-related adverse events and complications, and enhance satisfaction degree of doctors to nurses in operation room.

Objective     To compare the clinical efficacy of subxiphoid video-assisted thoracoscopic surgery (XVATS) and conventional intercostal VATS (CVATS) extended thymectomy for myasthenia gravis (MG). Methods    The clinical data of MG patients who underwent extended thymectomy in the Department of Thoracic Surgery of Xuzhou Central Hospital from October 2016 to October 2021 and finished the follow-up were retrospectively reviewed. They were divided into an XVATS group and a CVATS group according to the procedure. The perioperative variables and clinical efficacy of the two groups were compared. Results    A total of 84 patients were collected, including 43 males and 41 females, with a mean age of 52.3 years. There were 41 patients in the XVATS group and 43 patients in the CVATS group. There was no mortality, cardiopulmonary thrombosis, prolonged air leak, or mediastinal infection. Additionally, the CVATS group recorded 5 (11.6%) patients of conversion to open thoracotomy, 1 (2.3%) patient of postoperative MG crisis, 1 (2.3%) patient of bleeding in thorax, and 1 (2.3%) patient of chylothorax. The operation time (127.4±50.4 min vs. 122.9±38.6 min), intraoperative bleeding [46.9 (25.7, 79.2) mL vs. 45.7 (21.9, 92.1) mL], incidence of complications [0 vs. 7.0% (3/43)], chest tube duration (4.3±1.9 d vs. 4.8±2.8 d), follow-up time (19.1±8.5 months vs. 22.5±13.7 months), the proportion of residual mediastinal fat tissue [12.2% (5/41) vs. 4.7% (2/43)], and total MG remission rate [29.3% (12/41) vs. 51.2% (22/43)] were not statistically different between the two groups (P>0.05). However, the two groups showed  significantly different incidence of conversion to open thoracotomy [0 vs. 11.6% (5/43), P=0.024], postoperative hospital stay time (8.2±3.3 d vs. 11.4±5.8 d, P=0.003) and total drainage volume [396.7 (173.8, 542.5) mL vs. 218.8 (102.1, 430.0) mL, P=0.038]. Conclusion    XVATS extended thymectomy is technically safe and feasible; however, more evidence is warranted before the recommendation of this approach for the treatment of MG.

Objective:To evaluate the relationship between the preoperative neutrophil/lymphocyte ratio(NLR) and postoperative delirium (POD)in elderly patients.Methods:Nine hundred and thirty-seven patients, undergoing elective knee or hip arthroplasty under combined spinal and epidural anesthesia, in whom Mini-Mental State Examination was completed at 1 day before operation, with Mini-Mental State Examination score≥24, were selected. Elbow venous blood samples were collected before surgery, neutrophils and lymphocytes were counted, and the ratio of neutrophils to lymphocytes was calculated.Cerebrospinal fluid (CSF) 2 ml was extracted after successful spinal-epidural puncture for measurement of preoperative amyloid beta40 (Aβ40), amyloid beta42 (Aβ42), total Tau (T-tau), and phosphorylated Tau (P-tau) by enzyme-linked immunosorbent assay. POD was assessed by Confusion Assessment Method, and the severity of POD was assessed by the Memorial Delirium Assessment Scale.The logistic regression equation was used to identify the risk factors for POD, and the mediating effect of CSF biomarkers was analyzed. Sensitivity analysis was used to test the stability of the results. The receiver operating characteristic curve was introduced, and the area under the curve was calculated to evaluate the accuracy of preoperative NLR in predicting POD.Results:A total of 853 patients were finally enrolled in this study, and 17.4% patients developed POD. Logistic regression analysis showed that the increased levels of NLR ( OR 1.141, 95% confidence interval [ CI] 1.033-1.260, P=0.010), P-tau in CSF ( OR 1.093, 95% CI 1.076-1.110, P<0.001) and T-tau in CSF( OR 1.003, 95% CI 1.001-1.005, P<0.001) were risk factors for POD, while the increased level of Aβ42 in CSF( OR 0.998, 95% CI 0.997-1.000, P=0.028) was a protective factor for POD after adjusting for multiple confounding factors. Analysis of mediating effect: T-tau and P-tau in CSF were the mediating factors in the relationship between NLR and POD with the mediating effects of 0.011 9 and 0.020 0 respectively, and the proportion of mediating effect was 46.1% and 53.1% respectively.The receiver operating characteristic curve showed that the area under the curve of NLR and combination of NLR and CSF biomarkers in predicting POD was 0.711 and 0.939 respectively. Conclusions:Increased preoperative NLR level is a risk factor for POD, and combination of NLR and CSF biomarkers shows a higher accuracy in predicting POD. T-tau and P-tau in CSF serve as the key mediators in the relationship between NLR and POD.

ObjectiveTo evaluate the effect and safety of Buyang Huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis in the patients with syndrome of Qi deficiency and blood stasis and explore the possible anti-fibrosis mechanism of Buyang Huanwutang. MethodSixty-six patients with connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis were randomized to receive either Buyang Huanwutang combined with routine therapy or routine therapy for 4 weeks. The primary outcome indicator was change in forced vital capacity （FVC） from the baseline， and the secondary outcome indicators included the changes in percentage of predicted forced vital capacity （FVC%pred）， percentage of forced expiratory volume in first second to predicted value （FEV₁%pred）， King's Brief Interstitial Lung Disease （K-BILD） total score， 6 minute walking distance （6MWD）， hydroxyproline （HYP）， matrix metalloproteinase （MMP）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， and transforming growth factor-β （TGF-β） from baseline. Patients in line with the inclusion criteria were included in the primary analysis， and sensitivity analysis was performed after multiple imputation of missing data. Safety set was adopted for safety analysis. ResultThe 66 patients （included in the sensitivity analysis） meeting the inclusion criteria included 34 in the observation group and 32 in the control group， and 60 patients finally received the whole trial intervention （included for primary analysis）. Compared with the baseline， the FVC increased in the observation group and decreased in the control group after intervention （P<0.01）， which was consistent between the sensitivity analysis and the primary analysis. The changes in FVC%pred， FEV₁%pred， 6MWD， and K-BILD total score from baseline in the observation group were superior to those in the control group （P<0.01）， with consistent results between the sensitivity analysis and the primary analysis. TIMP-1 in the observation group decreased compared with baseline （P<0.05）， while TIMP-1 in the two groups showed no significant changes from the baseline The observation group outperformed the control group in the changes in HYP， MMP-9， and TGF-β from baseline （P<0.05）. The common adverse events were cough， diarrhea， nausea， rash， and upper gastrointestinal tract infection， the incidence of which showed no statistical difference between the two groups. ConclusionBuyang Huanwutang can improve lung function， motor function， and quality of life in patients with connective tissue disease-associated pulmonary fibrosis and has good safety. The mechanism may be related to the reduction of TGF-β， MMP-9， and TIMP-1 levels and maintaining of MMP-9/TIMP-1 balance.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To evaluate the relationship between preoperative levels of serum uric acid (SUA) and postoperative delirium (POD).Methods:Seven hundred and fifty patients of either sex, aged 50-90 yr, with American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective knee replacement under spinal-epidural anesthesia, were selected.Venous blood samples were collected before anesthesia and levels of SUA were determined by enzyme-coupled assay.L 3-4 was selected as the puncture space, and the cerebrospinal fluid (CSF) specimens were obtained from the subarachnoid space for determination of concentrations of β-amyloid 42, total tau (t-tau) and phosphorylated tau (p-tau) by enzyme-linked immunosorbent assay.The patients were divided into hyperuric acid group (group HS) and non-hyperuric acid group (group NS) according to clinical diagnostic criteria of hyperuricemia, and into POD group (group POD) and non-POD group (group NPOD) according to the occurrence of POD.Logistic regression was used to identify the risk factors for POD.The mediating effect of CSF biomarkers was analyzed.The efficacy of SUA and CSF biomarker concentrations in predicting POD was evaluated using the receiver operating characteristic curve. Results:A total of 699 patients were finally enrolled in the study, and the incidence of POD was 21.5%.The results of logistic regression analysis after adjusting for multiple confounding factors, such as age, sex, years of education, Mini-Mental State Examination score, smoking history, drinking history, hypertension and diabetes history, showed that increased concentrations of SUA and p-tau and t-tau in CSF were risk factors for POD ( P<0.05). The results of mediation analysis showed that the concentrations of p-tau and t-tau in CSF were the mediating factors of the relationship between SUA and POD, with mediating effects of 0.000 301 (95% confidence interval 0-0.000 152) and 0.000 236 (95% confidence interval 0-0.000 092), respectively, and the intermediary proportion were 14.9% and 11.7%, respectively.The area under the receiver operating characteristic curve of SUA in predicting POD was 0.774 ( P<0.05). Conclusions:Increased preoperative SUA is a risk factor for POD, and the accuracy of predicting POD is high, and concentrations of p-tau and t-tau in CSF are mediators of SUA affecting POD.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.