Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory receptor mainly expressed on active T-cells, or natural killer cells (NK cells) that activate negative stimulus signals in immune cells by combining with multiple ligands on the surface of target cells including tumor cells and infected cells. TIGIT plays an important regulatory role in the immune pathogenesis of tumors, viral infections and various autoimmune diseases by inhibiting the over activation of cells and the over secretion of proinflammatory cytokines. Recent researches show that TIGIT is highly expressed in T cells and NK cells of cancer patients, and is related to disease progression and poor clinical prognosis. Researchers try to enhance the activity of T cells or NK cells by blocking the binding of TIGIT and its ligand for therapeutic intervention. At present, there have been many reports about the use of anti-TIGIT monoclonal antibody treatment in different mouse tumor models leading to tumor regression, TIGIT has received extensive attention in cancer immunotherapy as a promising target for next generation cancer immunotherapy. Several clinical trials are currently evaluating the efficacy of anti-TIGIT monoclonal antibodies (mAbs) in patients with several cancers. The most advanced candidate, tiragolumab, has exhibited remarkable efficacy in programmed cell death ligand 1 (PD-L1)-positive non-small cell lung carcinoma (NSCLC) patients in phase Ⅱ clinical trials, in combination with PD-L1 blockade. However, the specific mechanism of TIGIT blockade remains to be fully elucidated.

OBJECTIVES: To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics. METHODS: Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers. RESULTS: There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP. CONCLUSIONS Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.
Infant, Newborn ; Infant ; Humans ; Tandem Mass Spectrometry ; Infant, Premature ; Chromatography, Liquid ; Retinopathy of Prematurity/diagnosis* ; Glutamic Acid ; Ornithine

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Outcome Assessment, Health Care ; Reference Standards ; Reproducibility of Results ; Research Design ; Clinical Trials as Topic

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To establish and validate analytic performance of laboratory-developed real-time quantitative polymerase chain reaction (RQ-PCR) test (LDT) for BCR::ABL1 p210 transcript.Methods:Using the primes and probes released by the Europe Against Cancer Program(EAC), we have established BCR::ABL1 p210 RQ-PCR test. The laboratory-specific conversion factor (CF) was determined by the WHO 1 st International Genetic Reference Panel, and a two-level internal control is developed using a mixture of K562 and HL60 cell lines was created to ensure traceability. Analytical performance, including analytical accuracy, analytical precision, linearity range, analytic sensitivity and specificity of RQ-PCR LDT test for BCR::ABL1 p210 transcript were validated according to CLIS guidelines. Furthermore, a comparison was made with an FDA-cleared RQ-PCR in vitro diagnostics (IVD) kit by Bland-Altman analysis. Results:The laboratory specific conversion factor (CF) for LDT RQ-PCR was determined to be 0.535 based on WHO 1 st International Genetic Reference Panel, which can be used to convert to the BCR::ABL international scale (BCR::ABL1 IS) reliably. The repeatability of BCR::ABL1 IS results at 4 different molecular response (MR0.5,MR1.5,MR2.5,MR3.5) levels are 7.44%, 5.33%, 9.12% and 18.06%, respectively, with total precision of 7.99%, 5.49%, 10.95% and 17.99%. The previous CAP proficiency test (PT) results from our laboratory were within the acceptable range of variation. MR results of our laboratory and MR mean value of all CAP-PT laboratory is highly correlated ( r=0.999, P<0.01), and consistent according to Bland-Altman analysis. Furthermore, the LDT method in our laboratory has a high correlation with the test results of FDA-cleared Qiagen IVD kit ( r=0.997, P<0.01). BCR::ABL1 IS results of BCR::ABL1 e13a2 transcript showed linearity within the range of 0.001%-7.454%, with a maximum coefficient of variation (% CV) 64.09%. The linearity range of e14a2 transcript BCR::ABL1 IS was 0.002%-12.398%, with a maximum % CV of 43.37%. The test has a limit of detection (LoD) of MR5.0 (0.001% IS) for e13a2 and MR4.8 (0.002% IS) for e14a2 transcript, respectively. The limit of quantitation (LoQ) for both e13a2 and e14a2 transcripts was MR4.7 (0.002% IS). The test exhibited 100% specificity, with no cross-reactivity observed between the p190 transcript and p210. Conclusions:The analytic performance of BCR::ABL1 p210 LDT RQ-PCR test from our laboratory is excellent, which can meet the clinical needs of BCR::ABL1 detection in patients with chronic myeloid leukemia.

Objective: To summarize short-term postoperative complications of transanal total mesorectal excision (taTME) in the treatment of middle-low rectal cancer. Methods: A descriptive case series of cases was constructed. Clinical data of consecutive 83 patients with mid-low rectal cancer who received taTME treatment from November 2016 to April 2021 at Department of General Surgery of Beijing Friendship Hospital, Capital Medical University were collected. Among 83 patients, 58 (69.9%) were males, with a mean age of (61.4±11.8) years; 42 (50.6%) were low rectal cancer, 41 (49.4%) were middle rectal cancer. Short-term postoperative complication was defined as complication occurring within 30 days after operation. The complication was graded according to the Clavien-Dindo classification. At the same time, the morbidity of short-term postoperative complication in the first 40 patients and that in the last 43 patients were compared to understand the differences before and after passing the taTME learning curve. Results: Two patients (2.5%) were converted to laparotomy ; 78 (94.0%) completed anastomosis.While 5 (6.0%) underwent permanent stoma. The total operation time of transabdominal+ transanal procedure was (246.9±85.0) minutes, and the median intraoperative blood loss was 100 (IQR: 100) ml. Seventy-five cases (75 /78, 96.2%) underwent defunctioning stoma, including 74 cases of diverting ileostomy, 1 case of diverting transverse colostomy and 3 cases without stoma. The morbidity of complication within 30 days after operation was 38.6% (32/83), and the morbidity of complication after discharge was 8.4% (7/83). Minor complications accounted for 31.3% (26/83) and major complications accounted for 7.2% (6/83). No patient died within 30 days after operation. The incidence of anastomotic leakage was 15.4% (12/78). Eight patients (9.6%) were hospitalized again due to complications after discharge. The median postoperative hospital stay was 7 (IQR: 3) days. All the patients with minor (I-II) complications received conservative treatment. One patient with grade C anastomotic leakage was transferred to intensive care unit and received a second operation due to sepsis and multiple organ dysfunction. Two patients with paralytic ileus (Clavien-Dindo IIIa) underwent endoscopic ileus catheter placement. There were 3 patients with Clavien-Dindo III or above respiratory complications, including 1 patient with pleural effusion and ultrasound-guided puncture, 2 patients with respiratory failure who were improved and discharged after anti-infection and symptomatic treatment. One patient underwent emergency ureteral stent implantation due to urinary infection (Clavien-Dindo IIIb). The morbidity of postoperative complication in the first 40 cases was 50.0% (20/40), and that in the latter 43 cases decreased significantly (27.9%, 12/43), whose difference was statistically significant (χ(2)=4.270, P=0.039). Conclusions: The procedure of taTME has an acceptable morbidity of short-term postoperative complication in the treatment of mid-low rectal cancer. The accumulation of surgical experience plays an important role in reducing the morbidity of postoperative complication.
Aged ; Anal Canal/surgery* ; Anastomotic Leak/etiology* ; Female ; Humans ; Male ; Middle Aged ; Operative Time ; Proctectomy/methods* ; Rectal Neoplasms/surgery*

ObjectiveWe aimed to investigate the efficacy and mechanism of Yishen Shengjing Prescription （YSP） in the treatment of oligoasthenospermia in rats. MethodThe oligoasthenospermia rat model was established by injection with cyclophosphamide （35 mg·kg^-1·d^-1） for 5 consecutive days. Rats were randomly assigned into control group （without treating with cyclophosphamide）， model group， low- （YSP-L）， medium- （YSP-M）， and high- （YSP-H） dose （2.91， 5.83， and 11.66 g·kg^-1， respectively） groups， Wuzi Yanzongwan （WYW， 1.03 g·kg^-1） group， and L-carnitine （0.17 g·kg^-1） group， with 8 rats in each group. After 28 days of drug intervention， the body weight， testicular weight， and testicular index of rats were recorded. The sperm quality in epididymis was detected by computer-assisted sperm analysis （CASA） system. Hematoxylin-eosin （HE） staining was employed for observation of testicular tissue morphology. The levels of malondialdehyde （MDA） and superoxide dismutase （SOD） in testicular tissue were detected by colorimetry. The levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and testosterone （T） in serum were determined by enzyme-linked immunosorbent assay（ELISA）. TdT-mediated dUTP nick-end labeling （TUNEL） was employed to detect the apoptosis of testicular cells. The protein levels of B cell lymphoma-2（Bcl-2）， Bax， and cleaved Caspase-3 in testicular tissue were detected by Western blot. ResultCompared with the control group， the model group showed decreased body weight， testicular weight and index， sperm concentration and motility （P<0.01） and increased testicular pathological score （P<0.01）. Compared with the model group， the YSP-M， YSP-H， WYW， and L-carnitine groups showed increased body weight， testicular weight， testicular index， sperm concentration and motility and decreased testicular pathological score. After modeling， the SOD level decreased （P<0.01） while the MDA content increased （P<0.01） in the testicular tissue. YSP-H， WYW， and L-carnitine reversed the SOD and MDA level changes caused by modeling. Compared with the control group， the model group exhibited declined T level （P<0.01） and increased FSH and LH levels （P<0.01）. Compared with the model group， YSP， WYW， and L-carnitine increased the T level （P<0.01） and decreased the LH level （P<0.05， P<0.01）. The apoptosis rate of spermatogenic cells in the model group was higher than that in the control group （P<0.01）， whereas YSP-M， WYW， and L-carnitine reversed such changes （P<0.01）. The model group rats showed decreased expression of Bcl-2（P<0.05） and increased expression of Bax and cleaved Caspase-3 （P<0.05， P<0.01）. Compared the model group， YSP-M， YSP-H， WYW， and L-carnitine up-regulated the Bcl-2 expression and down-regulated the cleaved Caspase-3 expression （P<0.05， P<0.01）. ConclusionYSP improved the sperm quality of oligoasthenospermia model rats by regulating the antioxidant system and sex hormone levels and inhibiting the apoptosis of spermatogenic cells.

Objective:To investigate the incidence and influencing factors of parastomal hernia in patients with permanent colostomy.Methods:The retrospective cohort study was conduc-ted. The clinicopathological data of 72 patients with permanent colostomy in the Beijing Friendship Hospital of Capital Medical University from January 2016 to June 2020 were collected. There were 50 males and 22 females, aged (66±12)years. Observations indicators: (1) follow-up; (2) analysis of factors affecting the incidence of parastomal hernia; (3) comparison of the incidence of parastomal hernia in patients with different age. Follow-up was conducted using outpatient examination. Patients were followed up once every 12 months after surgery to detect the incidence of parastomal hernia up to September 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers and percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model. Kaplan-Meier method was used to draw the parastomal hernia occurrence curve and calculate the incidence rate of parastomal hernia and Log-rank test was used to analyze the incidence of parastomal hernia. Results:(1) Follow-up. All 72 patients were followed up for 23(range, 12?76)months. During the follow-up, there were 31 patients developed parastomal hernia, with the incidence as 20.8%(15/72), 36.1%(26/72) and 43.1%(31/72) at postoperative 1 year, postoperative 2 year and postoperative 5 year, respectively. Of the 31 patients with parastomal hernia, there were 21 cases of type Ⅰ, 3 cases of type Ⅱ and 7 cases of type Ⅲ. Patients with parastomal hernia recovered with conservative treatment. (2) Analysis of factors affecting the incidence of parastomal hernia. Results of univariate analysis showed that age, subcutaneous fat thickness and rectus abdominis thickness were related factors affecting the incidence of parastomal hernia ( χ2=7.98, t=?2.95, 2.02, P<0.05). Results of multivariate analysis showed that age, subcutaneous fat thickness and rectus abdominis thickness were independent factors affecting the incidence of parastomal hernia ( odds ratio=4.07, 3.19, 0.07, 95% confidence interval as 1.46?11.32, 1.43?7.09, 0.01?0.84, P<0.05). (3) Comparison of the incidence of parastomal hernia in patients with different age. Of the 72 patients, there were 37 cases with age <65 years and 35 cases with age >65 years. Of the 31 patients with parastomal hernia, there were 10 cases with age<65 years and all of them with type Ⅰ parastomal hernia, and the incidence of parastomal hernia in postoperative 1 year and postoperative 2 year was 13.5%(5/37) and 27.0%(10/37), respectively. There were 21 cases with age ≥65 years and cases with type Ⅰ, type Ⅱ and type Ⅲ parastomal hernia were 11, 3 and 7, respectively. The postoperative 1 year and postoperative 2 year incidence of parastomal hernia in the 21 cases was 28.6%(10/35) and 45.7%(16/35), respectively. There was a significant difference in the incidence of parastomal hernia between patients<65 years and ≥65 years ( χ2=9.28, P<0.05). Conclusion:Age, subcutaneous fat thickness and rectus abdominis thickness are independent factors affecting the incidence of parastomal hernia.

Objective:To investigate the relationship between blood pressure variability (BPV) and incidence of post-traumatic stress disorder (PTSD) in trauma patients.Methods:Patients admitted to the department of emergency medicine of the Affiliated Hospital of Xuzhou Medical University for acute trauma from January 2018 to December 2021 were enrolled. The clinical data and blood pressure at admission (T1), 10 minutes before anesthesia (T2), 60 minutes after surgery (T3), and 24 hours after surgery (T4) were collected. Coefficient of variation of blood pressure variation [CV-BP, including coefficient of variation of systolic blood pressure (CV-SBP), coefficient of variation of diastolic blood pressure (CV-DBP), coefficient of variation of mean arterial pressure (CV-MAP)] and its quartile were calculated. Patients were divided into Q1 group (CV-MAP ≤ 7.27), Q2 group (7.27 < CV-MAP ≤ 9.50), Q3 group (9.50 < CV-MAP ≤ 14.05) and Q4 group (CV-MAP > 14.05) according to CV-MAP quartile. The PTSD symptoms of the patients were evaluated using the PTSD scale (PCL-5) one month later, and the patients were divided into the PTSD group and the non-PTSD group according to whether PCL-5 score higher than 38. Then the differences of the above indicators were compared and analyzed. Spearman correlation analysis was used to analyze the relationship between each index and PCL-5 score; the risk factors of PTSD were analyzed by univariate binary Logistic regression. Variables with P < 0.05 were included in the multivariate binary Logistic regression model. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of CV-MAP on the incidence of PTSD. Results:A total of 112 patients were enrolled, including 24 in PTSD group and 88 in non-PTSD group. Compared with non-PTSD group, the proportion of women, T1 shock index, proportion of intraoperative and postoperative blood transfusion in PTSD group was higher. Besides, PTSD group also had longer PT, more intraoperative and postoperative blood transfusion, and lower postoperative hemoglobin (Hb) level (all P < 0.05). The T1 SBP, DBP, MAP and T4 MAP of patients in PTSD group were significantly lower than those in non-PTSD group [T1 SBP (mmHg, 1 mmHg≈0.133 kPa): 105.0 (86.3, 121.3) vs. 122.0 (112.0, 132.8), T1 DBP (mmHg): 62.5 (50.0, 77.3) vs. 76.0 (68.5, 82.8), T1 MAP (mmHg): 77.8 (60.4, 91.3) vs. 93.3 (82.5, 99.0), T4 MAP (mmHg): 83.8±9.1 vs. 88.7±10.4, all P < 0.05], CV-SBP, CV-DBP and CV-MAP were higher than those in the non-PTSD group [CV-SBP: 12.80 (10.12, 19.16) vs. 9.30 (6.07, 12.95), CV-DBP: 16.62±6.47 vs. 12.40±5.61, CV-MAP: 14.10 (9.25, 18.85) vs. 8.90 (6.93, 13.29), all P < 0.05]. Spearman correlation analysis showed that there was a positive correlation between CV-MAP and PCL-5 scores in patients with acute trauma ( r = 0.429, P < 0.001); multivariate binary Logistic regression analysis showed that only CV-MAP [odds ratio ( OR) = 1.128, 95% confidence interval (95% CI) was 1.015-1.254, P = 0.025] and CV-DBP ( OR = 1.114, 95% confidence interval (95% CI) was 1.016-1.221, P = 0.022) was the risk factor for PTSD in acute trauma patients. Compared with Q1 group, Q4 group was significantly more likely to develop PTSD ( OR = 18.6, 95% CI was 1.9-179.1, P = 0.012). CV-SBP, CV-DBP and CV-MAP had certain predictive value on PTSD diagnosis in patients with acute trauma according to ROC curve analysis results [area under the ROC curve (AUC) was 0.713, 0.682 and 0.726, respectively], among which CV-MAP has the highest predictive value. When the cut-off value of CV-MAP was 12.158, the sensitivity was 75.0% and the specificity was 69.3%. Conclusion:Higher BPV after trauma is a risk factor for PTSD. Maintaining stable blood pressure in trauma patients is of great significance for prevention and treatment of PTSD.