The environmental and socioeconomic effects of tuberculosis patients in the southwest of China: a population-based study.

OBJECTIVE: The objective of this study was to assess the incidence of tuberculosis (TB) and find the risk factors of TB patients with a high burden of TB in socioeconomic level, the high level of TB incidence and the great changes of economic and social factors, explore the possible factors, construct scientific and robust prediction model, and analyse whether the task of stopping TB can be accomplished by the expected global deadline. STUDY DESIGN: This was an ecological study. METHODS: Descriptive analysis, spatial and space-time scan, correlation analysis, and regression analysis were carried out, based on cases of TB in Sichuan Province and ecological data from 2006 to 2017, to explore the characters of TB and ecological factors, using the transfer function-noise model to forecast the trend of TB until 2035. RESULTS: Factors affecting the incidence of TB, increasing per capita green area, reporting status of TB among Tibetans and Yi minorities, comprehensive treatment management, total cost of TB per capita for urban residents, proportion of males with high school education, 20 to 20 h of 24-h accumulated precipitation, reducing HIV at the same time as AIDS deaths, the increase in the proportion of males in junior high school education, and the increase in the number of registered TB cases can reduce the incidence of TB. CONCLUSIONS: There was concentration mainly on enhanced control of the environment and society measures, helpful in guiding government planning to control TB. Reinforcement is required to reduce the TB of population aged 15-24 and aged 25-64 in socioeconomic level by 2035.

[Clinical characteristics and efficacy analysis of various treatments for spontaneous carotid artery dissection].

Objective: To investigate the clinical features of spontaneous carotid artery dissection (SCAD) and the efficacy of different treatment methods. Methods: The clinical data of 164 patients with SCAD who were treated at the First Affiliated Hospital of Zhengzhou University from June 2018 to January 2023 were retrospectively analyzed. There were 127 males and 37 females, with a mean age of (49.5±11.1) years. They were divided into conservative treatment group (n=100) and surgical treatment group (n=64) according to whether they received surgical treatment. Patients were followed at 3, 6, and 12 months after discharge and annually thereafter through outpatient or inpatient visits. The incidence of cerebral ischemic events, cerebral hemorrhage events, and mortality rates during hospitalization and follow-up periods were analyzed in the two patient groups. To examine correlates of revascularization in SCAD, multifactorial logistic regression analysis was used. Results: Of the 164 patients, 18 patients had bilateral SCAD and a total of 182 carotid arteries were included in the study. Ischemic stroke (85 cases, 51.8%) and transient ischemic attack (31 cases, 18.9%) were the main clinical manifestations in SCAD patients. Hypertension (81 cases, 49.4%) and hyperlipidemia (39 cases, 23.8%) were the main comorbidities in SCAD patients. During hospitalization, 100 patients in the conservative treatment group received medication in 113 carotid arteries, no new cerebral ischemic events or symptomatic intracranial hemorrhage events occurred, and no death occurred. A total of 69 carotid arteries were surgically treated in 64 patients in the surgical treatment group. The success rate was 97.1% (67/69). In the surgical treatment group, the proportion of carotid stenosis degree≥90% was 47.8% (33/69), the proportion of type Ⅱ SCAD was 60.9% (42/69), and the proportion discharged from the hospital to receive antiplatelet therapy was 92.8% (64/69), which were higher than those in the conservative treatment group, which were 25.7% (29/113), 45.1% (51/113), and 73.5% (83/113), respectively (all P<0.05). The follow-up time [M(Q1, Q3)] in the conservative treatment group was 24 (13, 34) months, with an 8% (9/113) rate of ischemic events and a 7.1% (8/113) rate of readmission; in the surgical treatment group, the follow-up time was 24 (11, 38) months, and there were no new ischemic events or deaths. The results of multifactorial logistic regression analysis showed that the degree of true luminal stenosis<90% (OR=2.738, 95%CI: 1.067-7.026, P=0.036) and type Ⅰ dissections (OR=2.656, 95%CI: 1.189-5.935, P=0.017) were the correlates of complete revascularization. Conclusions: Ischemic stroke and transient ischemic attack are the main clinical manifestations in patients with SCAD. Pharmacological antithrombotic therapy remains the method of choice, and endovascular treatment after failure of conservative therapy reduces the risk of recurrent long-term cerebral ischemic events and the re-admission rate of patients.

[Clinicopathological features of intravascular large B-cell lymphoma and collision tumors of five cases].

Objective: To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) and its collision tumors. Methods: Five cases of IVLBCL were collected, including 2 cases of collision tumors, and 1 case complicated with liver cirrhosis. The morphology and immunophenotype were analyzed. The related literature was reviewed. Results: There were 2 females and 3 males, aged from 53 to 73 years, with a median age of 65 years. The tumors were located in the lower extremities, right cerebellar hemisphere, left kidney, bilateral nasal cavity, and liver, respectively. Cases 2 and 3 were incidentally found in meningioma and renal cell carcinoma tissues, respectively. Case 5 had a background of liver cirrhosis. Morphologically, atypical large lymphoid cells were located in small blood vessels and capillary lumen, with little cytoplasm, hyperchromasia, prominent nucleoli, and obvious mitotic figures. Immunohistochemically, the IVLBCL tumor cells expressed CD20 and PAX5; 2 cases were CD5 positive. One of the 5 cases was GCB phenotype, and 4 cases were non-GCB phenotype. All cases expressed C-MYC (positive rate was 10%-40%). PD-L1 was positive in 4 cases (positive rate was 60%-90%). Ki-67 proliferation index was 70%-90%. CKpan, CD3, TDT, and CD34 were negative. In case 2, meningioma cells were positive for PR, EMA, and vimentin, but negative for CKpan and PD-L1. In case 3, renal carcinoma cells were positive for CKpan, PAX8, EMA, vimentin, CAⅨ and CD10, while PD-L1 was negative. No EBER expression (by in situ hybridization) or C-MYC gene translocation (FISH, break-apart probe) was detected in any of the 5 cases. Three patients were followed up, and all died within 1-13 months. Conclusions: IVLBCL is a highly aggressive lymphoma, with occult clinical manifestations and poor prognosis. Collision tumors of IVLBCL are extremely rare. A better understanding of IVLBCL would help pathologists avoid misdiagnoses.

[Mid- and long-term results of surgical treatment of brachiocephalic Takayasu arteritis].

Objective: To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis. Methods: This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates. Results: All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%. Conclusion: For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient's condition,and the mid-and long-term outcomes are satisfactory.

On-chip phase-shift induced control of supercontinuum generation in a dual-core Si3N4 waveguide.

We investigate on-chip spectral control of supercontinuum generation, taking advantage of the additional spatial degree of freedom in strongly-coupled dual-core waveguides. Using numerical integration of the multi-mode generalized nonlinear Schrödinger equation, we show that, with proper waveguide cross-section design, selective excitation of supermodes can vary the dispersion to its extremes, i.e., all-normal or anomalous dispersion can be selected via phase shifting in a Mach-Zehnder input circuit. The resulting control allows to provide vastly different supercontinuum spectra with the same waveguide circuit.

[Efficacy and safety of superpulse thulium laser lithotripsy in the intracavitary treatment of urinary calculi].

Objective: To evaluate the efficacy and safety of superpulse thulium laser lithotripsy in the intracavitary treatment of urinary calculi. Methods: From May 2021 to July 2022, patients diagnosed with urinary calculi were screened in four medical centers. Those who met the criteria were treated with superpulse thulium fiber laser under endoscope. The patients' perioperative conditions were recorded. The main effective index was stone-free rate (SFR) 4 weeks after operation, the main safety index was the failure rate of the experimental instruments during operation, and the secondary safety index was the incidence rate of perioperative complications. Results: A total of 76 eligible patients completed superpulse thulium fiber laser lithotripsy, with an average age of (52.0±11.1) years, 54 males and 22 females. There were 31 renal stones, 43 ureteral stones and 2 bladder stones. Percutaneous nephrolithotomy was performed in 17 patients. Ureteroscopy lithotripsy/flexible ureteroscopy lithotripsy was performed in 57 patients and transurethral bladder lithotripsy was in 2 patients. The lithotripsy time of all patients was (50.9±31.4) minutes. There was no failure of experimental instruments during the operation. Six patients refused follow-up examination after operation. The incidence of postoperative adverse events was 61.8% (47/76). One patient needed hospitalization due to inguinal hernia after operation, and the rest were classified as Clavien-dindo grade 1-2. The SFR was 94.3% (66/70) at 4 weeks after operation. Conclusion: It is effective and safe to use superpulse thulium fiber laser in the treatment of urinary calculi.

[Development and implementation of common data sets for venous thromboembolism: current situation and application prospects].

Venous thromboembolism (VTE) is a formidable disease that poses a serious threat to the health and well-being of hospitalized patients. Owing to its high incidence, debilitating morbidity, and alarming mortality rates, VTE has gained increasing attention from the clinical medicine community worldwide. Unfortunately, the current state of clinical prevention and treatment of VTE is not very optimistic, necessitating the establishment of large disease-specific databases and real-world studies, which can accumulate effective evidence-based medical evidence to gradually standardize the clinical prevention and treatment and quality control of VTE. The construction and development of large medical databases depend greatly on standardized datasets, which establish the conceptual data models of VTE through data standardization routes, set the object classes according to the model, define the attributes of the classes, standardize the data types and property values, and organize the standardized data elements. This article focuses on providing an in-depth overview of the unique characteristics of various domestic and foreign VTE datasets, describing their application and research progress in VTE, as well as the role of datasets in standardizing clinical and research practices to strengthen quality control and artificial intelligence. Through this comprehensive discussion, we hope to promote the establishment of VTE datasets and enable their use in high-quality large real-world studies.

[Efficacy and safety of high-voltage pulsed radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia].

Objective: To investigate the efficacy and safety of high-voltage pulse radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia (PHN). Methods: A total of 103 patients with PHN who were admitted to the Department of Pain Medicine of Henan Provincial People's Hospital from May 2020 to May 2022 were retrospectively selected, including 50 males and 53 females, and aged 40 to 79 (65.4±9.2) years. The patients were divided into two groups according to the treatment methods they received: the control group (n=51) and the study group (n=52). The patients in the control group were treated with oral pregabalin, and the patients in the study group received pregabalin plus high-voltage pulse radiofrequency therapy. The pain intensity and efficacy of the two groups were evaluated before treatment and 4 weeks after treatment. The pain intensity, the sleep quality and the efficacy of treatment was evaluated by visual analogue scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score and nimodipine method, respectively. The levels of pain mediators including serum neuropeptide Y (NPY), prostaglandin E2 (PGE2), substance P (SP) and ß-endorphin were measured. The differences of the above indicators and the incidence of adverse reactions were compared between the two groups. Results: The VAS scores of the study group and the control group before treatment were 7.94±0.76 and 8.20±0.81, and PSQI scores were 16.84±3.90 and 16.29±3.84, respectively, with no statistically significant differences (both P>0.05). After 4 weeks of treatment, the VAS scores of the two groups were 2.84±0.80 and 3.35±0.87, and PSQI scores were 6.78±1.90 and 7.98±2.40, respectively, and the VAS score and PSQI score in the study group were lower than those in the control group (both P<0.05). There were no significant differences of the serum levels of NPY, PGE2, SP and ß-endorphin before treatment in the study group and control group (all P>0.05). After 4 weeks of treatment, the levels of NPY, PGE2, SP and ß-Endorphin in the study group were (240.7±26.8) ng/L, (74.4±8.6) µg/L, (108.9±15.7) ng/L and (4.4±0.9) ng/L, which were lower than those in the control group [(268.1±29.4) ng/L, (79.7±8.3) µg/L, (115.2±16.2) ng/L, (5.2±1.3) ng/L, respectively], with statistically significant differences (all P<0.05). After treatment, 29 cases were cured, 16 cases were markedly effective and 6 cases were effective in the study group, while 16 cases, 24 cases and 8 cases were cured, markedly effective and effective in the control group, respectively. The overall efficacy of patients in the study group was better than that in the control group (Z=-2.32, P=0.018). The incidence of adverse reactions in the study group and control group was 11.5% (6/52) and 7.8% (4/51), respectively, with no statistically significant difference (χ2=0.40, P=0.527). Conclusion: High-voltage pulse radiofrequency combined with pregabalin can significantly improve the pain intensity and sleep quality of patients with severe thoracic PHN and reduce the levels of pain mediators, with a high safety profile.

[Efficacy and safety of high-voltage pulsed radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia].

Objective: To investigate the efficacy and safety of high-voltage pulse radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia (PHN). Methods: A total of 103 patients with PHN who were admitted to the Department of Pain Medicine of Henan Provincial People's Hospital from May 2020 to May 2022 were retrospectively selected, including 50 males and 53 females, and aged 40 to 79 (65.4±9.2) years. The patients were divided into two groups according to the treatment methods they received: the control group (n=51) and the study group (n=52). The patients in the control group were treated with oral pregabalin, and the patients in the study group received pregabalin plus high-voltage pulse radiofrequency therapy. The pain intensity and efficacy of the two groups were evaluated before treatment and 4 weeks after treatment. The pain intensity, the sleep quality and the efficacy of treatment was evaluated by visual analogue scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score and nimodipine method, respectively. The levels of pain factors including serum neuropeptide Y (NPY), prostaglandin E2 (PGE2), substance P (SP) and ß-Endorphin were measured. The differences of the above indicators and the incidence of adverse reactions were compared between the two groups. Results: The VAS scores and PSQI scores of the study group and the control group before treatment were (7.94±0.76), (8.20±0.81), (16.84±3.90) and (16.29±3.84), respectively, with no statistically significant difference (both P>0.05). After 4 weeks of treatment, the VAS scores and PSQI scores of the two groups were (2.84±0.80), (3.35±0.87), (6.78±1.90) and (7.98±2.40), respectively, and the VAS score and PSQI score in the study group were lower than those in the control group (both P<0.05). Serum levels of NPY, PGE2, SP and ß-Endorphin were (298.5±31.0) ng/L, (92.3±11.0) µg/L, (156.8±21.4) ng/L, and (8.6±1.6) ng/L in the study group and (304.2±28.6) ng/L, (94.4±12.9) µg/L, (152.7±23.8) ng/L and (8.2±1.8) ng/L in the control group, with no significant differences (all P>0.05). After 4 weeks of treatment, levels of NPY, PGE2, SP and ß-Endorphin were (240.7±26.8) ng/L, (74.4±8.6) µg/L, (108.9±15.7) ng/L and (4.4±0.9) ng/L, which were lower than those in the control group [(268.1±29.4) ng/L, (79.7±8.3) µg/L, (115.2±16.2) ng/L, (5.2±1.3) ng/L, respectively], with statistically significant differences (all P<0.05). After treatment, 29 cases were cured, 16 cases were markedly effective and 6 cases were effective in the study group, while 16 cases, 24 cases and 8 cases were cured, markedly effective and effective in the control group. The overall efficacy of patients in the study group was better than that in the control group (Z=-2.32, P=0.018). The incidence of adverse reactions in the study group and control group was 11.5% (6/52) and 7.8% (4/51), respectively, with no statistically significant difference (χ2=0.40, P=0.527). Conclusion: High-voltage pulse radiofrequency combined with pregabalin can significantly improve the pain and sleep quality of patients with severe thoracic PHN and reduce the level of pain factors, with a high safety profile.

[Efficacy and safety of pulsed radiofrequency combined with gabapentin in the treatment of acute herpetic neuralgia].

Objective: To explore the clinical efficacy and safety of pulsed radiofrequency (PRF) combined with gabapentin in the treatment of acute herpetic neuralgia (AHN). Methods: A total of 123 AHN patients were retrospectively selected in Henan Provincial People's Hospital from November 2019 to July 2022, who were divided into two groups based on treatment methods: control group (treated with gabapentin, n=61) and study group (treated with gabapentin and PRF, n=62). The visual analog scale (VAS) was utilized for pain severity assessment and the self-rating scale for sleep (SRSS) was utilized for sleep quality evaluation. The differences in serum levels of interleukin (IL)-10, chemokine ligand 10 (CXCL-10), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), IL-2 and IL-6 before and after treatment were compared between the two groups. The overall treatment effectiveness and the occurrence rates of postherpetic neuralgia and adverse reactions were evaluated in both groups. Results: Among the study group patients, 28 were male and 34 were female, and the age was (62.8±8.5) years. Among the control group patients, 35 were male and 26 were female, and the age was (64.0±7.8) years. The VAS scores of the study group before and after treatment were 7.96±1.33 and 1.52±0.60, respectively, while the control group were 7.68±1.52 and 2.70±0.64. The SRSS scores before and after treatment in the study group were 31.74±5.90 and 12.06±2.81, respectively, while those in the control group were 33.10±5.54 and 14.14±2.96, respectively. Before treatment, there were no statistically differences of the VAS scores and SRSS scores in both groups (all P>0.05). After treatment, the VAS scores and SRSS scores in both groups decreased compared with before treatment (all P<0.05), the study group's VAS scores and SRSS scores were lower than those in the control group (all P<0.05). Before treatment, there were no statistically differences of the serum levels of IL-10, CXCL-10, PGE2, COX-2, IL-2 and IL-6 in both groups (all P>0.05). After treatment, the serum levels of IL-10, CXCL-10, PGE2, COX-2 and IL-6 in both groups decreased compared with before treatment, while the IL-2 level increased. Additionally, the study group had lower serum levels of IL-10, PGE2, COX-2 and IL-6 compared with the control group (all P<0.05). After treatment, the study group had 35 cases of cure, 26 cases of effectiveness, and 1 case of ineffectiveness, while the control group had 22 cases of cure, 31 cases of effectiveness, and 8 cases of ineffectiveness. The overall treatment efficacy of the study group was better than that of the control group (P=0.012). The incidence of postherpetic neuralgia in the study group after treatment was 16.1% (10/62), which was lower than that in the control group, which was 37.7% (23/61) (P<0.05). There were no statistically differences of the occurrence rates of adverse reactions in both groups (all P>0.05). Conclusion: Combining PRF with gabapentin for the treatment of AHN demonstrates better overall efficacy and safety, which can more effectively alleviate pain, improve sleep, and reduce inflammatory cytokine levels.

[Factors influencing bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt].

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.

[Evaluation considerations for using surrogate endpoints in anticancer clinical trials].

The prolongation of patient's overall survival is the accepted as gold standard to prove clinical values of anti-cancer drugs. However, if overall survival is taken as the primary endpoint in clinical trials for cancer types with a relatively good prognosis in the process of new anti-cancer drug research and development, the time to market the drugs will be prolonged due to the long follow-up time. In addition, overall survival is often interfered by confounding factors such as follow-up treatment. Therefore, regulatory agencies have established an accelerated review model using surrogate endpoints for the approval of new anti-cancer drugs, but there are still some problems in the use of surrogate endpoints in cancer clinical trials. From the perspective of new drug review, the authors expounds the key points of confirming and rationally using surrogate endpoints in clinical trials of anti-cancer drugs, which will improve the level of clinical trials of new anti-cancer drugs and accelerate the development of anti-tumor drugs.

[Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported].

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

[Recommendations on the diagnosis and treatment of osteoarthritis in China].

Osteoarthritis (OA) is the most common form of arthritis and the leading cause of old age disability, affecting an estimated 302 million people worldwide. OA is seriously overlooked in the world. The awareness of OA and the popularization of standardized diagnosis and treatment are all lacking. Knees, hips, and hands are the most commonly affected joints in OA. Based on the experience of diagnosis and treatment, consensus and guidelines, we formulated this diagnosis and treatment standard in order to standardize the diagnosis and treatment of OA. We hope that our standard can reduce misdiagnosis and mistreatment and improve the prognosis of OA.

[Immune-related genes and their determined immune cell microenvironment to predict the prognosis of gastric adenocarcinoma].

Objective: Through bioinformatics analysis to screen key immune-related genes (IRGs) and cancer-related pathways in gastric adenocarcinoma (GAC) therapy, combining immune cell microenvironment to predict the prognosis of GAC. Methods: RNA sequencing and clinical data were obtained from public databases. Differentially expressed IRGs between GAC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, we established the risk signature model and found another database for external validation. In addition, we explored the relationship with the immune cell microenvironment in each GAC sample using CIBERSORT algorithms. Results: A total of 78 differentially expressed IRGs were screened, including 47 up-regulated and 31 down-regulated genes. Subsequently, a five-IRGs signature (BMP8A、MMP12、NRG4、S100A9 and TUBB3) was significantly associated with the overall survival of GAC patients. Survival analysis indicated that patients in the high-risk group have a poor prognosis. The results of the multivariate analysis revealed that the risk score was an independent prognostic factor. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and GEO validated cohorts. Besides, the results of tumor-infiltrating immune cell analysis indicated that the risk score could reflect the status of the tumor immune microenvironment. Conclusion: BMP8A, MMP12, NRG4, S100A9 and TUBB3 with the risk signature model are associated with prognosis in patients with GAC, combined with tumor-infiltrating immune cells to provide new markers for immunotherapy in GAC.

[Evaluation of severity and prognosis of acute pancreatitis by CT severity index and modified CT severity index].

Objectives: To explore the role of computed tomography (CT) severity index (CTSI) and modified CT severity index (MCTSI) in assessing the severity of acute pancreatitis (AP) under the revised Atlanta classification (RAC) and predicting the clinical prognosis. Methods: Based on the prospectively entered AP database, the clinical data of consecutive adult AP inpatients admitted to the Department of Gastroenterology of the First Affiliated Hospital of Nanchang University from January 2012 to December 2020 were retrospectively screened. The imaging data were independently evaluated by two radiologists and entered to the database to calculate the CTSI and MCTSI scores. Their relationship with the difference of RAC severity grade and clinical prognosis was analyzed. Compared with Acute Physiology and Chronic Health Assessment Ⅱ (APACHE Ⅱ) score, the receiver operating characteristic curve was used to evaluate the predictive value of CTSI and MCTSI scores for persistent organ failure and infectious pancreatic necrosis (IPN). Results: A total of 2 612 patients with AP, aged (50±15) years, were included in the study, including 1 547 males (59.2%) and 1 065 females (40.8%). According to RAC standard, AP was divided into 699 cases (26.8%) of mild pancreatitis (MAP), 1 098 cases (42.0%) of moderately severe pancreatitis (MSAP), and 815 cases (31.2%) of severe pancreatitis (SAP). MCTSI judged AP severity similarly to RAC, with 668 cases of MAP (25.6%), 1 207 cases of MSAP (46.2%) and 737 cases of SAP (28.2%), while CTSI judged SAP patients less(400 cases, 15.3%). The severity of AP determined by CTSI and MCTSI scores was significantly correlated with clinical prognosis (r=0.06-0.43, all P<0.05). Compared with APACHE Ⅱ score, CTSI had the highest area under the curve (AUC) for predicting IPN (AUC=0.85, 95%CI: 0.83-0.87), followed by MCTSI (AUC=0.82, 95%CI: 0.80-0.85). APACHE Ⅱ was more accurate in predicting persistent organ failure than CTSI and MCTSI scores,with AUC of 0.73 (95%CI: 0.71-0.75), 0.72 (95%CI: 0.70-0.74) and 0.72 (95%CI: 0.70-0.74), respectively. Conclusions: AP severity judged by MCTSI is consistent with RAC, and SAP patients judged by CTSI are less than RAC. CTSI and MCTSI are significantly correlated with clinical prognosis. CTSI and MCTSI have higher accuracy in predicting IPN, but lower accuracy in predicting persistent organ failure than APACHE Ⅱ.

[Clinicopathological features of mixed cervical carcinoma with adenoid cystic pattern].

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular characteristics, differential diagnosis, clinical treatment and prognosis of mixed carcinoma of cervix with adenoid cystic pattern. Methods: Three cases of mixed cervical carcinoma with adenoid cystic pattern were collected at the Affiliated Hospital of Xuzhou University Medical School from 2018 to 2021.The clinicopathological characteristics were analyzed, immunohistochemistry (IHC) and in situ hybridization (ISH) were performed. The related literature was reviewed. Results: The three patients were postmenopausal women with a median age of 74.7 years. The clinical symptom was vaginal bleeding without obvious causes. One case was an endophytic tumor, and the others were exophytic. The median diameter of the three cases was 3.3 cm. Two patients underwent hysterectomy, the tumors infiltrated the external 1/3 and middle 1/3 of the cervix respectively. All the lymph nodes were negative. One patient had a previous biopsy. Microscopically, all three tumors were characterized by a cribriform structure, which were filled with basophilic myxoid substance and surrounded by tubules lined by two layers of cells. The tumor cells had scanty cytoplasm and showed the characteristics of cervical basal-like cells. All three cases were accompanied by high-grade squamous intraepithelial lesions and squamous cell carcinoma, and one also showed a non-specific spindle cell sarcomatoid component. Within the double-layered epithelial structure, the outer epithelium was positive for p63, CD117, p16INK4a (clone E6H4) and MYB protein and negative for S-100 by IHC. The combined positive score of PD-L1 (clone 22C3) was less than 1 in all three cases. Human papillomavirus (HPV) types 16 and 18 were detected in one patient preoperatively, while high-risk HPV were positive in the other two patients by RNAscope ISH postoperatively. None of the three cases showed MYB gene rearrangement by FISH. The mean follow-up time was 23.3 months (36, 28 and 6 months, respectively). Two patients underwent hysterectomy and radiotherapy survived without disease. One patient survived with tumor just by radiotherapy and drug therapy. Conclusions: Mixed cervical carcinoma with adenoid cystic pattern is extremely rare. It is a high-grade malignancy with poor prognosis. The tumor is associated with high-risk HPV infection, without MYB gene rearrangement, and with low PD-L1 immunoreactivity. Radical surgery combined with radiotherapy and chemotherapy is the mainstay of treatment at present.

[Mechanisms of quorum sensing regulating antimicrobial resistance].

Antimicrobial resistance is a major threat to human health, so new strategies are urgently needed to impede antimicrobial resistance. Quorum sensing is an intracellular communication system that is activated to regulate downstream gene transcription when the population density reaches a threshold. Quorum sensing regulates drug resistance by altering biofilm formation and dispersion, efflux pump expression, and bacterial secretion systems, making it a promising target of overcoming antimicrobial resistance. To date, various quorum sensing inhibitors have been found to block quorum sensing by degrading signal molecules, interfering with the recognition and binding of signal molecules and receptors, and interrupting the synthesis of quorum sensing signals. Hence, quorum sensing inhibitors are expected to become a new way to control antimicrobial resistance.

Linoleic acid and α-linolenic acid inhibit conjugative transfer of an IncX4 plasmid carrying mcr-1.

AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

Ventilation and air cleaning to limit aerosol particle concentrations in a gym during the COVID-19 pandemic.

SARS-CoV-2 can spread by close contact through large droplet spray and indirect contact via contaminated objects. There is mounting evidence that it can also be transmitted by inhalation of infected saliva aerosol particles. These particles are generated when breathing, talking, laughing, coughing or sneezing. It can be assumed that aerosol particle concentrations should be kept low in order to minimize the potential risk of airborne virus transmission. This paper presents measurements of aerosol particle concentrations in a gym, where saliva aerosol production is pronounced. 35 test persons performed physical exercise and aerosol particle concentrations, CO2 concentrations, air temperature and relative humidity were obtained in the room of 886 m³. A separate test was used to discriminate between human endogenous and exogenous aerosol particles. Aerosol particle removal by mechanical ventilation and mobile air cleaning units was measured. The gym test showed that ventilation with air-change rate ACH = 2.2 h-1, i.e. 4.5 times the minimum of the Dutch Building Code, was insufficient to stop the significant aerosol concentration rise over 30 min. Air cleaning alone with ACH = 1.39 h-1 had a similar effect as ventilation alone. Simplified mathematical models were engaged to provide further insight into ventilation, air cleaning and deposition. It was shown that combining the above-mentioned ventilation and air cleaning can reduce aerosol particle concentrations with 80 to 90% , depending on aerosol size. This combination of existing ventilation supplemented with air cleaning is energy efficient and can also be applied for other indoor environments.