Huanglian Jiedu Wan intervened with "Shi-Re Shanghuo" syndrome through regulating immune balance mediated by biomarker succinate.

With increasing stress in daily life and work, subhealth conditions induced by "Shi-Re Shanghuo" syndrome was gradually universal. "Huanglian Jiedu Wan" (HLJDW) was the first new syndrome Chinese medicine approved for the treatment of "Shi-Re Shanghuo" with promising clinical efficacy. Preliminary small-sample clinical studies have identified some notable biomarkers (succinate, 4-hydroxynonenal, etc.). However, the correlation and underlying mechanism between these biomarkers of HLJDW intervention on "Shi-Re Shanghuo" syndrome remained ambiguous. Therefore, this study was designed as a randomized, double-blind, multicenter, placebo-controlled Phase II clinical trial, employing integrated analysis techniques such as non-targeted and targeted metabolomics, salivary microbiota, proteomics, parallel peaction monitoring, molecular docking and surface plasmon resonance (SPR). The results of the correlation analysis indicated that HLJDW could mediate the balance between inflammation and immunity through succinate produced via host and microbial source to intervene "Shi-Re Shanghuo" syndrome. Further through the HIF1α/MMP9 pathway, succinate regulated downstream arachidonic acid metabolism, particularly the lipid peroxidation product 4-hydroxynonenal. Finally, an animal model of recurrent oral ulcers induced by "Shi-Re Shang Huo" was established and HLJDW was used for intervention, key essential indicators (succinate, glutamine, 4-hydroxynonenal, arachidonic acid metabolism) essential in the potential pathway HIF1α/MMP9 discovered in clinical practice were validated. The results were found to be consistent with our clinical findings. Taken together, succinate was observed as an important signal that triggered immune responses, which might serve as a key regulatory metabolic switch or marker of "Shi-Re Shanghuo" syndrome treated with HLJDW.

Comparison of Intercostal Block and Epidural Analgesia for Post-thoracotomy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Thoracotomy is associated with severe postoperative pain. Effective management of acute pain after thoracotomy may reduce complications and chronic pain. Epidural analgesia (EPI) is considered the gold standard for postthoracotomy analgesia; however, it is associated with complications and limitations. Emerging evidence suggests that an intercostal nerve block (ICB) has a low risk of severe complications. Anesthetists will benefit from a review that assesses the advantages and disadvantages associated with ICB and EPI in thoracotomy. OBJECTIVES: This meta-analysis aimed to evaluate the analgesic efficacy and adverse effects of ICB and EPI for pain treatment after thoracotomy. STUDY DESIGN: Systematic review. METHODS: This study was registered in the International Prospective Register of Systematic Reviews (CRD42021255127). Relevant studies were searched for in PubMed, Embase, Cochrane, and Ovid databases. Primary (postoperative pain at rest and during cough) and secondary (nausea and vomiting, morphine consumption, and length of hospital stay) outcomes were analyzed. The standard mean difference for continuous variables and the risk ratio for dichotomous variables were calculated. RESULTS: Nine randomized controlled studies with a total of 498 patients who underwent thoracotomy were included. The results of the meta-analysis demonstrated no statistically significant differences between the 2 methods in terms of the Visual Analog Scale scores for pain at 6-8, 12-15, 24-25, and 48-50 hours at rest and at 24 hours during coughing after surgery. There were no significant differences in nausea and vomiting, morphine consumption, or length of hospital stay between the ICB and EPI groups. LIMITATIONS: The number of included studies was small, and the quality of evidence was low. CONCLUSIONS: ICB may be as effective as EPI for pain relief after thoracotomy.

Integrated transcriptomics and lipidomics investigation of the mechanism underlying the gastrointestinal mucosa damage of Loropetalum chinense (R.Br.) and its representative component.

BACKGROUND: Loropetalum chinensis (R.Br) Oliv (Bhjm), a Chinese folk herbal medicine, was traditionally used in the treatment of wound bleeding and skin ulcers. A new drug named JIMUSAN granules used for gastrosia was developed by our group, and clinical trials have been approved. However, as the principal herb, the material basis and underlying mechanisms of Bhjm in attenuating gastrointestinal mucosa damage (GMD) remain to be systemically illuminated. PURPOSE: An integrated strategy was used to explore the therapeutic effects and mechanisms of Bhjm and ellagic acid (EA) on GMD zebrafish, using network pharmacology, transcriptomics, lipidomics, and real-time quantitative PCR (RT-qPCR) verification. METHODS: First, network pharmacological analysis was used to infer the major effective constituents and targets of Bhjm. Ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UHPLC-LTQ-Orbitrap HRMS) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) were employed to identify the chemical constituents and quantify the different types of constituents. Second, zebrafish model of GMD was established by using 2,4,6-trinitrobenzenesulfonic acid (TNBS) to evaluate the efficacy of Bhjm and EA. The potential mechanism was examined by integrated transcriptomics and lipidomics analysis. Finally, validation tests were implemented using RT-qPCR. RESULTS: In this study, targets indentified by network pharmacology were related to inflammation and mucosal damage. Ten representative components that interacted with these targets were simultaneously determined by UHPLC-MS/MS. Sixty four compounds were identified or tentatively characterized, most of which were flavonoids and polyphenols. Bhjm and EA alleviated mucosal damage and reduced inflammation in a TNBS-induced zebrafish GMD model, indicating that EA was the main active compounds. Eight common differentially expressed genes were downregulated by Bhjm and EA, as determined by transcriptomics analysis. Lipidomics analysis confirmed 12 differential lipids, including phosphatidylcholine (PC) and triglyceride (TG). Further network enrichment analysis demonstrated that differential lipid metabolism was regulated by klf4 and hist1h2ba, and were validated by RT-qPCR. CONCLUSION: In our study, the chemical profile of Bhjm was clarified. Moreover, the GMD repair effect and the mechanism of Bhjm and EA was comprehensively analyzed for the first time, involving inflammation and lipid metabolism. Collectively, these findings will be significantly helpful for deeply exploring the clinical application value of Bhjm.

[Determination and comparison of 10 active components in different parts of Loropetalum chinensis based on ultra-high performance liquid chromatography-tandem mass spectrometry].

To establish a method for the simultaneous determination of ellagic acid, quercetin, gallic acid, kaempferol, myricetin, tiliroside, salidroside, isoquercetin, chlorogenic acid, and quinic acid in the leaves, flowers, fruits, and roots of Loropetalum chinensis by ultra-performance liquid chromatography-tandem mass spectrometry, and provide references for the development and utilization of L. chinensis resources. The analysis was performed on the chromatographic column ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 µm) with a gradient mobile phase of acetonitrile-0.2% formic solution at the flow rate of 0.3 mL·min~(-1). Column temperature was 30 ℃ and injection volume was 2 µL. Multiple reactive ion monitoring mode(MRM) was used in the negative ion ionization mode of electrospray ion source. The 10 active components had a good linear relationship, and the established method was stable, simple, and accurate. The 10 active components existed in different parts of L. chinensis, with significant different content. The main components in different parts of L. chinensis were polyphenols, with the highest content, followed by flavonoids. The content of 10 active components was generally high in flowers. Among them, the content of quinic acid was the highest, reaching 22.539 1 mg·g~(-1). This study elucidates the differences of active components in the same part and the different parts of L. chinensis, thereby providing basis for the research on the pharmacodynamic substances of L. chinensis and references for the comprehensive development and utilization of L. chinensis resources.

Location of motor branches of tibialis posterior muscle and its relation in treatment of spastic equinovarus foot: a cadaveric study.

BACKGROUND AND OBJECTIVES: Nerve block or neurolysis is an important approach in the treatment of spastic equinovarus foot. To illustrate the accurate location of the nerve branch to the tibialis posterior muscle (TP) in clinical practice, 21 adult cadavers were dissected and 14 complete both lower limb specimens were obtained. A total of 28 lower limbs were included. METHODS: We measured the length of the motor branch nerve (LM) of the tibialis posterior muscle, the length of the fibula (LF), the vertical distance (D1) from the midpoint of LM to the fibula tip as well as the horizontal distance (D2) from the midpoint of LM to the inner edge of the fibula. RESULTS: The LM was higher (35.74 ± 7.28 mm) in male than in female (30.40 ± 6.88 mm) specimens but there was no significant correlation between LM and gender (p > 0.05). Additionally, among male specimens, the LM on the right side was longer than that on the left (p ≤ 0.05) while among female specimens, the D1 on the left side was longer than that on the right (p ≤ 0.05). The LF in male specimen was significantly longer than that in female (p ≤ 0.05). The midpoint of the nerve to the motor branch of the tibialis posterior muscle was about 50 mm distal to the fibular head and 10 mm at the inner edge of the fibula. CONCLUSION: Using this coordinate, the midpoint of the nerve branch to the TP could be accurately located.

P3H4 Overexpression Serves as a Prognostic Factor in Lung Adenocarcinoma.

BACKGROUND: The present study is aimed at evaluating the functional and clinical values of P3H4 in lung adenocarcinoma. Moreover, we also investigated the downstream pathways that P3H4 might participate in. METHODS: The differential expression analysis was used to identify genes differentially expressed in lung adenocarcinoma tissues as compared with normal tissues. Survival analysis was used to test the association between P3H4 and survival time. Gene set enrichment analysis was conducted to explore the downstream pathways. CCK8 and transwell were employed to examine the impact of P3H4 on cell phenotypes. RESULTS: P3H4 was highly upregulated in LUAD tissues at both RNA and protein levels. Moreover, the LUAD patients, who had high expression of P3H4, were also observed to have shorter disease-free survival and overall survival. These results demonstrated that P3H4 could be used as a prognostic biomarker for LUAD. Moreover, we also found that it was the copy number alterations (CNAs), not DNA methylation, that regulated the RNA expression of P3H4, indicating that its upregulation might be partially resulted from the CNAs. Furthermore, functional experiments revealed that the A549 and H1299 cells with siRNA treatment (siP3H4) exhibited significantly decreased cell proliferation after 24 hours, migratory ability, and invasiveness. Functionally, the upregulated proteins in the P3H4 high expression group were mainly enriched in tumor microenvironment-related pathways such as phagosome, focal adhesion, and ECM-receptor interaction and cancer-related pathways such as bladder cancer pathway, proteoglycans in cancer, and hippo signaling pathway. CONCLUSION: The present study systematically evaluated the functional and clinical values of P3H4 in LUAD, and explored the related biological pathways. P3H4 might promote LUAD progression through regulating tumor microenvironment-related pathways.

[Psychological care combined with enhanced recovery after surgery management in perioperative nursing care of andrological patients: A randomized controlled study].

OBJECTIVE: To evaluate the validity of psychological care combined with enhanced recovery after surgery (PC+ERAS) management in perioperative nursing care of andrological patients. METHODS: A total of 300 male patients undergoing andrological surgery were included in this study, 150 given PC+ERAS and the other 150 receiving routine nursing care as controls. We evaluated anxiety and depression of all the patients on admission and discharge using Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), and compared post-operative hospital days, off-bed time, first passage of flatus, Visual Analog Scale (VAS) score and satisfaction with nursing care between the two groups of patients. RESULTS: On discharge, significant improvement was observed in SAS and SDS scores in the PC+ERAS group compared with the baseline, even more significant than in the control group (P < 0.01), but no obvious improvement was seen in the controls (P > 0.05). The patients in the PC+ERAS group also achieved a significantly shorter post-operative hospital stay, earlier post-operative off-bed time and passage of flatus, lower VAS score, and higher satisfaction with nursing care than those in the control group (P < 0.05). CONCLUSIONS: Psychological care combined with ERAS management deserves wide application in the perioperative nursing care of andrological patients, which can significantly improve the patients' anxiety and depression, shorten post-operative hospital stay, reduce VAS score, and increase their satisfaction with nursing care.

Dicaffeoyl polyamine derivatives from bitter goji: Contribution to the bitter taste of fruit.

Although the bioactive compounds in goji have been thoroughly identified and quantified, little information is available on the bitter compounds in the berries, and no systematic works on the substances responsible for their bitterness have been performed. Herein, the substances contributing to the bitterness of berries were isolated and purified from bitter-tasting goji by the combined use of column chromatography and high-pressure liquid chromatography (HPLC). The bitterness of the isolated compounds was evaluated using a biosensor with immobilized rat taste-bud tissues. The structures were elucidated via comprehensive mass spectrometry (MS) and nuclear magnetic resonance (NMR) analyses. Seven spermine or spermidine alkaloids were identified, including four new compounds (lyciamarspermidines A and B and lyciamarspermines A and B). The intensities of the bitterness levels of the isolated compounds differed with the number of glucose substituents. These isolated compounds all contribute to the bitterness of goji. The results of this study provide opportunities for the further investigation of the bitterness of goji.

Learning curve for robot-assisted lobectomy of lung cancer.

BACKGROUND: Robotic lobectomy is widely used for lung cancer treatment. So far, few studies have been performed to systematically analyze the learning curve. Our purpose is to define the learning curve to provide a training guideline of this technique. METHODS: A total of 208 consecutive patients with primary lung cancer who underwent robotic-assisted lobectomy by our surgical team were enrolled in this study. Baseline information and postoperative outcomes were collected. Learning curves were then analyzed using the cumulative sum (CUSUM) method. Patients were divided into three groups according to the cut-off points of the learning curve. Intraoperative characteristics and short-term outcomes were compared among the three groups. RESULTS: CUSUM plots revealed that the docking time, console time and total surgical time in patients were 20, 34 and 32 cases, respectively. Comparison of the surgical time among the 3 phases revealed that the total surgical time (197.03±27.67, 152.61±21.07, 141.35±29.11 min, P<0.001), console time (150.97±26.13, 103.89±18.04, 97.49±24.80 min, P<0.001) and docking time (13.53±2.08, 11.95±1.10, 11.89±1.49 min, P<0.001) were decreased significantly. Estimated blood loss differed among groups (90.63±45.41, 87.63±59.84, 60.29±28.59 mL, P=0.001) and was associated with shorter operative time. There was no conversion or 30-day mortality. No significant differences were observed among other clinic-pathological characteristics among the groups. CONCLUSIONS: For a surgeon, the learning time of robotic lobectomy was in the 32th operation. For a bedside assistant, at least 20 cases were required to achieve the level of optimal docking.

Robotic circumferential tracheal resection and reconstruction via a completely portal approach.

Robotic surgery for circumferential tracheal resection and reconstruction has not previously been reported. Herein we describe the case of a 48-year-old man with primary extra-luminal tracheal leiomyosarcoma. A preoperative bronchoscopy exam and chest computed tomography revealed a tracheal neoplasm, which derived from lower membranous trachea and nearly obstructed the orifice of the left main bronchus. The patient underwent circumferential tracheal resection and reconstruction via a completely portal robotic approach with four arms. Benefitting from flexible instruments and a three-dimensional magnified view, telescope anastomosis was performed and modulated. No postoperative complications presented. Follow-up showed the reconstructed trachea without stenosis or recurrence.

A novel technique for identification of the segments based on pulmonary artery plane combined with oxygen diffusing discrepancy.

BACKGROUND: Segmentectomy has been widely accepted as a powerful tool to treat small lung nodules. Despite been commonly used, identify the intersegment plane precisely in visual during the operation still being a complex issue. We described a novel method in minimal invasive thoracic surgery utilizing arterial-navigation combined with oxygen diffusing discrepancy based on the variance of oxygen diffusion in target and reserved segments. We perspectively analyzed 24 cases with small lung nodules of T1N0M0 disease to examine the efficacy of the new method. METHODS: From June 2018 to September 2018, 24 patients with small primary lung cancers underwent segmentectomy at The Affiliated Hospital of Qingdao University. All the patients received minimally invasive procedures and standard anatomical segmentectomy. Ligation of the target segment artery followed by observation and the arterial-navigation line gradually appeared by color discrepancy in the visceral pleural surface. The plane was then testified by inflation-deflation method. RESULTS: The mean identification time of the intersegments plane was 8 minutes. The residual segments collapsed and stayed pink, meanwhile the target parts remained inflated and turned dark. It allowed a clear identification of the intersegments plane on the surface. All operations were successfully completed. There were no perioperative deaths or major complications. The coincidence rate of arterial-navigation and inflation-deflation technique was 22/24. CONCLUSIONS: The arterial-navigation method is safe and feasible to identify the intersegmental plane in small lung tumor resection.

Two-port approached thoracoscopic carina reconstruction using natural bronchial bifurcation.

BACKGROUND: Carina resection and reconstruction is a challenging procedure for thoracic surgeons. We describe a novel technique of thoracoscopic carina reconstruction using the natural bifurcation, following pulmonary resection of the lung neoplasm. To our knowledge, it is the first report of this kind. CASE PRESENTATION: A 71-year-old male diagnosed of squamous cell lung cancer received two-port approached video-assisted thoracoscopic right bilobectomy with carina resection after 2 cycles of neoadjuvant therapy. After the removal of right lower lobe and middle lobe, the 7 station lymph nodes were resected with the invaded carina and bronchial walls in an en-bloc fashion. The neocarina was reconstructed by the natural bifurcation between the right upper bronchus and the bronchus intermedius. Intraoperative blood loss was about 220 mL, and operative time was about 225 min. The postoperative course was uneventful. The pathological TNM stage was pT3N2M0, IIIA. Adjuvant chemotherapy using gemcitabine and cisplatin was administered for 4 cycles. Follow-up 6 months after surgery confirmed no stenosis and no signs of local recurrence by bronchoscopy and CT scan. CONCLUSIONS: We consider that the surgical procedure described here is a new alternative strategy for carina resection and reconstruction in the similar situation. The minimally invasive method is safe and effective for this challenging operation.

Potential targets for protecting against hippocampal cell apoptosis after transient cerebral ischemia-reperfusion injury in aged rats.

Mitochondria play an important role in neuronal apoptosis caused by cerebral ischemia, and the role is mediated by the expression of mitochondrial proteins. This study investigated the involvement of mitochondrial proteins in hippocampal cell apoptosis after transient cerebral ischemia-reperfusion injury in aged rats using a comparative proteomics strategy. Our experimental results show that the aged rat brain is sensitive to ischemia-reperfusion injury and that transient ischemia led to cell apoptosis in the hippocampus and changes in memory and cognition of aged rats. Differential proteomics analysis suggested that this phenomenon may be mediated by mitochondrial proteins associated with energy metabolism and apoptosis in aged rats. This study provides potential drug targets for the treatment of transient cerebral ischemia-reperfusion injury.

Chemical profiling and quantification of Chinese medicinal formula Huang-Lian-Jie-Du decoction, a systematic quality control strategy using ultra high performance liquid chromatography combined with hybrid quadrupole-orbitrap and triple quadrupole mass spectrometers.

To clarify and quantify the chemical profiling of Huang-Lian-Jie-Du decoction (HLJDD) rapidly, a feasible and accurate strategy was developed by applying high speed LC combined with hybrid quadrupole-orbitrap mass spectrometer (Q-Exactive) and UHPLC-triple quadruple mass spectrometer (UHPLC-QqQ MS). 69 compounds, including iridoids, alkaloids, flavonoids, triterpenoid, monoterpene and phenolic acids, were identified by their characteristic high resolution mass data. Among them, 18 major compounds were unambiguously detected by comparing with reference standards. In the subsequent quantitative analysis, 17 representative compounds, selected as quality control markers, were simultaneously detected in 10 batches of HLJDD samples by UHPLC-QqQ MS. These samples were collected from four different countries (regions). Icariin, swertiamarin and corynoline were employed as internal standards for flavonoids, iridoids and alkaloids respectively. All the analytes were detected within 12min. Polarity switching mode was used in the optimization of multiple reaction monitoring (MRM) conditions. Satisfactory linearity was achieved with wide linear range and fine determination coefficient (r(2)>0.9990). The relative standard deviations (RSD) of inter- and intra-day precisions were less than 5.0%. This method was also validated by repeatability, stability (8h) and recovery, with respective RSDs less than 4.6%, 5.0% and 6.3%. This research established a high sensitive and efficient method for the integrating quality control, including identification and quantification of Chinese medicinal formulas.