Cost-Utility Analysis of Tenofovir Alafenamide and Entecavir in Chronic Hepatitis B Patients: A Markov Decision Model.

From the perspective of health economics, the evaluation of drug-related cost effectiveness and clinical utility is crucial. We conducted a cost-utility analysis of two first-line drugs, tenofovir alafenamide (TAF) and entecavir (ETV), in the treatment of chronic hepatitis B (CHB) patients. We performed inverse probability of treatment weighting (IPTW) to match the independent variables between the two treatment groups. The incremental cost effectiveness ratio (ICER) of the two treatment groups was simulated using a decision tree with the Markov annual-cycle model. A total of 54 patients treated with TAF and 98 with ETV from January 2016 to December 2020 were enrolled. The total medical cost in the TAF group was NT$76,098 less than that in the ETV group, and TAF demonstrated more effectiveness than ETV by 3.19 quality-adjusted life years (QALYs). When the time horizon was set at 30 years, the ICER of the TAF group compared with the ETV group was -NT$23,878 per QALY, suggesting more cost savings for TAF. Additionally, with the application of TAF, over NT$366 million (approximately US$12 million) can be saved annually. TAF demonstrates cheaper medical costs and more favorable clinical QALYs than ETV. To balance health insurance benefits and cost effectiveness, TAF is the optimal treatment for CHB.

Exploring the interwoven relationship: Property rights, financial freedom, government regulation, and stock market fluctuations in emerging economies - A novel system GMM perspective.

This study delves into the impact of formal institutions on stock market volatility within a selection of emerging economies. Specifically, it examines the role that formal institutions play in shaping this volatility. To accomplish our goal, we analyze panel data from 46 emerging nations spanning the years 2000-2019, utilizing system generalized method of moments (GMM), as well as random and fixed effect models for our estimations. The findings of this research validate the existence of a significant association between formal institutions and stock market volatility. Likewise, through dynamic panel estimation, we discover that formal institutions such as property rights, financial freedom, and government regulations have a notable negative effect on stock market volatility. Consequently, this study implies that formal institutions play a crucial role in reducing stock market volatility in emerging economies, fostering their development. The insights gained from this research encourage policymakers to view formal institutions as key influencers of stock market volatility. These results offer valuable guidance for emerging nations.

Triarylamine-Functionalized Imidazolyl-Capped Bithiophene Hole Transporting Material for Cost-Effective Perovskite Solar Cells.

Triarylamine end-capped-functionalized arylene-imidazole derivatives were synthesized from readily accessible, inexpensive precursors and employed as hole transporting materials (HTMs) in perovskite solar cells (PSCs). All the HTMs displayed high thermal decomposition temperatures (>410 °C), which is beneficial for realizing stable PSC devices. In addition, the new HTMs show appropriate energy level alignment with the perovskite layer, ensuring efficient hole transfer from perovskites to HTMs. Interestingly, PSCs fabricated with the triarylamine-functionalized imidazolyl-capped bithiophene molecule (DImBT-4D) as the HTM exhibited the best power conversion efficiency of 20.11%, comparable to that of the benchmark HTM spiro-OMeTAD, prompting it be a prospective candidate for large-scale PSC applications.

Risk factors for central lymph nodes more than 5 involved in papillary thyroid microcarcinoma with cN0 / 中华内分泌外科杂志

Objective:To analyze the risk factors of the number of central lymph node metastasis (CLNM) >5 in papillary thyroid microcarcinoma (PTMC) with clinical lymph node negative (cN0) .Methods:A total of 1567 cases of unilateral cN0 PTMC patients undergoing surgery at Endocrine and Breast Surgery Department of the First Affiliated Hospital of Chongqing Medical University from Jan. 2013 to Dec. 2018 were analyzed retrospectively. There were 405 cases of male and 1162 cases of female among them. According to the CLNM, they were divided into 0-5 and ≥5 groups. Clinicopathological characteristics of two groups were compared with Chi-square test and χ 2 test, et al. Results:The case of CLNM>5 involved was 4.1% (65/1567) .Univariate analysis showed that male, age ≤50 years old, tumor diameter> 8 mm, multifocal cancer all were related to CLNM>5 involved ( P<0.05) , multivariate logistic regression analysis found that male ( OR=1.886, P=0.017) , age ≤50 years ( OR=3.778, P=0.002) , tumor diameter>8 mm ( OR=2.483, P<0.001) and multifocal cancer ( OR=2.362, P=0.005) were independent risk factors for CLNM>5. Subgroup analysis showed that the number of Delphian lymph nodes metastasis≥1 ( OR=13.475, P<0.001) , pretracheal lymph nodes metastasis≥2 ( OR=41.695, P<0.001) , and Delphian+pretracheal lymph nodes metastasis≥2 ( OR=28.750, P<0.001) were also independent risk factors for CLNM>5. Conclusions:Unilateral PTMC patients who are male and age ≤50 years old with tumor diameter>8 mm, multifocal cancer have higher risk of central lymph nodes more than 5 involved, surgical treatment and prophylactic central neck dissection are recommended to such patients instead of long-term follow-up observation.Total thyroidectomy should be selected appropriately according to the intraoperative situation.

Traditional Chinese Medicine Intervention of Ferroptosis Based on Yin-yang Theory： A Review / 中国实验方剂学杂志

Ferroptosis， a new type of iron-dependent programmed cell death， is related to multiple pathways such as glutathione/glutathione peroxidase 4， iron metabolism， lipid metabolism， and iron autophagy， and plays an important part in the occurrence and development of many diseases， such as tumor， cerebral ischemia， and Parkinson's disease. Ferroptosis is a double-edged sword as it can eliminate pathological cells （such as tumor cells） but long-term ferroptosis may cause or aggravate other disorders related to abnormal lipid metabolism and iron metabolism. Regulating the balance between cell proliferation and ferroptosis may be an important target for drug intervention in diseases. The Yin-yang theory is one of the foundational principles of traditional Chinese medicine （TCM）， which is used to explain the physiological functions and pathological changes of human body and to guide the diagnosis and prevention of disease and health care. The balance of cell proliferation and programmed death is essentially the balance of Yin and Yang at the cellular level， which is governed and regulated by the law of balance. TCM intervenes in ferroptosis by promoting ferroptosis of tumor cells （damaging the excess） and inhibiting ferroptosis of other diseases （compensating the deficiency）， which is similar to the treatment principle of adjusting Yin and Yang. On this basis， this article aims to use the Yin-yang theory to clarify the relationship between TCM promoting ferroptosis and inhibiting ferroptosis， which is expected to lay a basis for the modern application of Yin-yang theory and provide new targets for TCM treatment.

Mechanism of Orcinol Glucoside in Treatment of Osteoporosis： An Exploration Based on Network Pharmacology and in Vitro Validation / 中国实验方剂学杂志

ObjectiveTo predict the therapeutic targets and related signaling pathways of orcinol glucoside （OG） in the treatment of osteoporosis by network pharmacology， and further clarify its mechanisms based on molecular docking and in vitro cell model. MethodThe pharmacological targets of OG were obtained from Similarity ensemble approach （SEA） and SwissTargetPrediction， and the targets related to osteoporosis from DisGeNET and GeneCards. The cross-analysis was conducted to screen the common targets between OG and osteoporosis. STRING was used to construct the protein-protein interaction （PPI） network， followed by topology analysis using CytoNCA plug-in of Cytoscape 3.7.2 to screen out the core targets. The obtained common targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） analysis by g：Profiler. AutoDock Vina was utilized for molecular docking， and the in vitro cell experiments were then carried out for verifying the mechanism of OG in treating osteoporosis. ResultA total of 73 targets related to OG and osteoporosis were harvested，among which 14 were proved to be key targets by topological analysis. GO and KEGG functional enrichment analysis yielded 259 cell biological processes， mainly involving organonitrogen compound metabolic process， cell population proliferation， protein metabolic process， regulation of response to stress， and response to chemicals. Its mechanism of action might be related to advanced glycation end-product （AGE）-AGE receptor （RAGE） signaling pathway， interleukin-17 （IL-17） signaling pathway， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. Molecular docking indicated that the binding energies of OG to Cyclin D1 （CCND1） and cyclin-dependent kinase 4 （CDK4） were the lowest and similar. The results of flow cytometry showed that compared with the normal group， OG group exhibited decreased proportion of cells in G0/G1 phase （P<0.01） and decreased proportion of cells in S phase （P<0.01）. As demonstrated by Western blot， compared with the normal group， OG up-regulated the protein expression levels of Cyclin D1 and CDK4 （P<0.05， P<0.01）. ConclusionOG alleviates osteoporosis via multiple targets and multiple pathways. It may exert the therapeutic effects by increasing Cyclin D1 and CDK4 protein expression to change cell cycle and promote cell proliferation.

Investigation on the first family cluster of Chlamydia psittaci infection in Wuhan / 公共卫生与预防医学

Objective An epidemiological investigation was carried out on the first family cluster epidemic of psittacosis in Wuhan to provide scientific basis for the prevention and control of Chlamydia psittacosis. Methods Epidemiological data were collected by field epidemiological investigation methods, and pathogenic testing was carried out by collecting cases, suspected exposed persons, and environmental samples. Results The 2 cases in the same family stared with fever, headache and chills. The first case was treated in 5 medical institutions and hospitalized in 2 of them. The results of metagenomic next-generation sequencing in the bronchoalveolar lavage fluid of the case indicated that it was infected with Chlamydia psittaci. Thirty environmental samples from cases and 3 pigeon farmers homes, 4 throat swabs from family members of pigeon farmers were collected, and 15 environmental samples were positive by real-time fluorescence quantitative polymerase chain reaction, all of which were in the cases' home and neighbor farmers' homes, including 8 pigeon feces smearing samples, 3 pigeon drinking residual water samples, 1 sand and corn eaten by pigeons, 1 tableware surface smearing sample, and 1 sample of external environment of the patient's home. Conclusions The family cluster epidemic of psittacosis was caused by exposure to the external environment contaminated by Chlamydia psittacosis. Poultry breeding should be regulated to prevent the spread of poultry infection to the human world. At the same time, the awareness of medical staff should be raised, and pathogenic testing should be carried out to confirm the diagnosis for avoiding the occurrence of severe cases and death.

Impact of chronic obstructive pulmonary disease on postoperative complications and short-term prognosis in patients undergoing oesophagectomy / 中国胸心血管外科临床杂志

@#Objective    To provide clinical reference for the perioperative management of esophageal cancer patients with different stages of chronic obstructive pulmonary disease (COPD) through investigating the impact of COPD on postoperative complications and survival in esophageal cancer patients undergoing oesophagectomy. Methods    The clinical data of 163 patients who underwent radical resection of esophageal cancer in our department from January 2015 to January 2018 were retrospectively analyzed, including 124 males and 39 females, with a median age of 64 years (IQR: 23.8 years). They were divided into a COPD group (n=87) and a non-COPD group (n=76) according to the presence of COPD before operation. The clinical data were collected and the postoperative complications and 2-year survival between the two groups were compared and analyzed. Results    The incidence of major postoperative complications (pulmonary infection, respiratory failure, arrhythmia and anastomotic leakage) in the COPD group were higher than those in the non-COPD group (all P<0.05). Spearman correlation analysis showed that the severity of preoperative COPD was positively correlated with the incidence of postoperative complications in patients with esophageal cancer (r=0.437, P<0.001). The incidence of postoperative respiratory failure and mortality in patients with severe COPD were significantly higher than those in patients without COPD and those with mild or moderate COPD. The 2-year survival rate of patients with esophageal cancer in the COPD group was lower than that in the non-COPD group (56.1%vs. 78.5.%, P=0.001), and the severity of COPD was negatively correlated to the survival rate. Conclusion    COPD significantly increases the incidence of postoperative complications in patients with esophageal cancer, which is not conducive to the prognosis of patients, and the severity of COPD is correlated with postoperative complications and 2-year survival rate.

Cytoplasmic tail truncation of SARS-CoV-2 Spike protein enhances titer of pseudotyped vectors but masks the effect of the D614G mutation

The high pathogenicity of SARS-CoV-2 requires it to be handled under biosafety level 3 conditions. Consequently, Spike protein pseudotyped vectors are a useful tool to study viral entry and its inhibition, with retroviral, lentiviral (LV) and vesicular stomatitis virus (VSV) vectors the most commonly used systems. Methods to increase the titer of such vectors commonly include concentration by ultracentrifugation and truncation of the Spike protein cytoplasmic tail. However, limited studies have examined whether such a modification also impacts the proteins function. Here, we optimized concentration methods for SARS-CoV-2 Spike pseudotyped VSV vectors, finding that tangential flow filtration produced vectors with more consistent titers than ultracentrifugation. We also examined the impact of Spike tail truncation on transduction of various cell types and sensitivity to convalescent serum neutralization. We found that tail truncation increased Spike incorporation into both LV and VSV vectors and resulted in enhanced titers, but had no impact on sensitivity to convalescent serum inhibition. In addition, we analyzed the effect of the D614G mutation, which became a dominant SARS-CoV-2 variant early in the pandemic. Our studies revealed that, similar to the tail truncation, D614G independently increases Spike incorporation and vector titers, but that this effect is masked by also including the cytoplasmic tail truncation. Therefore, the use of full-length Spike protein, combined with tangential flow filtration, is recommended as a method to generate high titer pseudotyped vectors that retain native Spike protein functions. IMPORTANCEPseudotyped viral vectors are useful tools to study the properties of viral fusion proteins, especially those from highly pathogenic viruses. The Spike protein of SARS-CoV-2 has been investigated using pseudotyped lentiviral and VSV vector systems, where truncation of its cytoplasmic tail is commonly used to enhance Spike incorporation into vectors and to increase the titers of the resulting vectors. However, our studies have shown that such effects can also mask the phenotype of the D614G mutation in the ectodomain of the protein, which was a dominant variant early in the COVID-19 pandemic. To better ensure the authenticity of Spike protein phenotypes when using pseudotyped vectors, we therefore recommend using full-length Spike proteins, combined with tangential flow filtration methods of concentration, if higher titer vectors are required.

Gaps in COPD Guidelines of Low- and Middle-Income Countries: A Systematic Scoping Review.

BACKGROUND: Guidelines are critical for facilitating cost-effective COPD care. Development and implementation in low-and middle-income countries (LMICs) is challenging. To guide future strategy, an overview of current global COPD guidelines is required. RESEARCH QUESTION: We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation. STUDY DESIGN AND METHODS: Scoping review of national COPD management guidelines. We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socio-economic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards. LMICs guidelines were compared with those from high-income countries (HICs). RESULTS: Of the 61 national COPD guidelines identified, 30 were from LMICs. Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines. Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities. More than 90% of all guidelines included smoking cessation advice. Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%). LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05). LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P < .05). INTERPRETATION: Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation. Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated. Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources.

Analysis of cases with emergency thyroid surgery / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinical features of cases with emergency thyroid surgery. Methods: Nineteen cases treated with emergency thyroid surgery from May 2014 to May 2019 were analysed retrospectively, including 9 males and 10 females, aged from 24-79 years old. Among them, 6 cases had nodular goitres and 13 cases had thyroid malignancies. One case underwent tracheal stenting before operation. Emergency thyroid surgery was due to severe dyspnea in all cases. Treatment outcomes and prognoses of patients were evaluated. Results: All the 19 patients underwent general anesthesia with endotracheal intubation. One patient underwent extracorporeal membrane oxygenation(ECMO) and two patients underwent cardiopulmonary bypass. Six cases of nodular goitres underwent proximal thyroidectomy. Eight cases of malignant tumors underwent total thyroidectomy, six cases with invading the trachea underwent tracheal end-end anastomosis after partial tracheal resection, one case underwent tumor resection with sternal sternum approach, cervical and mediastinal lymph node dissection, total laryngectomy and tracheal low ostomy. Two cases with extensive involvement of malignant tumors were given a definite diagnosis and tracheostomy. Of three cases with malignant lymphoma, one underwent total thyroidectomy, and two were only given a definite diagnosis and tracheostomy. No complications such as hemorrhage, recurrent laryngeal nerve or parathyroid injury occurred after operation in all patients. With followed up for 6-50 months, except 2 cases died due to tumor progression, the rest were alive. Conclusions: Patients with obvious dyspnea caused by thyroid tumors have a high mortality rate and should be treated actively. Emergency surgery not only relieves respiratory obstruction and saves the lives of patients, but some patients can get a radical cure as well.

Intervention Effect of New Chinese Herbal Prescription Selected by Data Mining Against Decreased Ovarian Reserve in Rats / 中国实验方剂学杂志

Objective:To select and evaluate new Chinese herbal prescription for the treatment of decreased ovarian reserve （DOR） and its appropriate dosage. Method:The literature concerning the treatment of DOR with traditional Chinese medicine （TCM） was retrieved from such databases as Chinese Journal Full-text Database， Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP）， based on which a database was established using the Traditional Chinese Medicine Inheritance Support System （TCMISS） V2.5. The data mining was then carried out to obtain the core combinations of Chinese herbs and new Chinese herbal prescription combinations， followed by the determination of the new Chinese herbal prescription by expert group discussion for experiment evaluation. The female SD rats were divided into the normal group， DOR model group， Kuntai capsule group， and low-， medium-， and high-dose new Chinese herbal prescription groups， with 12 rats in each group. Rats in the Kuntai capsule group and low-， medium-， and high-dose new Chinese herbal prescription groups were treated with Kuntai capsule solution （0.5 g·kg^-1 determined according to the dosage in the instruction） and 3.037 5， 6.075， and 9.12 g·kg^-1 new Chinese herbal prescription， respectively. After 21 days， the estrous cycle was observed by vaginal exfoliated cell smear， and the ovarian structure was observed by hematoxylin-eosin （HE） staining. The serum anti-mullerian hormone （AMH）， follicle stimulating hormone （FSH）， luteinizing hormone （LH）， and estrogen （E₂） contents as well as the reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione （GSH） levels and superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） activities in ovary were detected using biochemical methods. Result:The new Chinese herbal prescription subjected to experimental evaluation was composed of 11 Chinese herbs， namely Rehmanniae Radix Praeparata 20 g， Cervi Cornus Colla 12 g， Lycii Fructus 20 g， Corni Fructus 12 g， Albiziae Cortex 9 g， Nelumbinis Plumula 3 g， Salviae Miltiorrhizae Radix et Rhizoma 20 g， Astragali Radix 30 g， Atractylodis Macrocephalae Rhizoma 12 g， Dioscoreae Rhizoma 30 g， and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle 6 g. Compared with the model group， the Kuntai capsule group and medium- and high-dose new Chinese herbal prescription groups exhibited significantly improved estrous cycle and follicular development， elevated serum AMH and E₂ and ovarian GSH （<italic>P</italic><0.05）， decreased serum FSH and LH （<italic>P</italic><0.05） and ovarian ROS and MDA （<italic>P</italic><0.05）， and enhanced SOD， CAT， and GSH-Px activities （<italic>P</italic><0.05）. There were no significant differences in the above-mentioned indexes between the Kuntai capsule group and the middle- and high-dose new Chinese herbal prescription groups， but the estrous cycle and follicular development were better in the latter two groups. Conclusion:The new Chinese herbal prescription screened by data mining is able to enhance ovarian antioxidation， promote follicular development， ameliorate serum hormone and estrous cycle， and effectively improve ovarian reserve function in DOR rats. The medium dose （6.075 g·kg^-1） has been proved optimal.

Echocardiographic parameters and indices in 23 healthy Maltese dogs

Background@#Echocardiography is a primary tool used by veterinarians to evaluate heart diseases. In recent years, various studies have targeted standard echocardiographic values for different breeds. Reference data are currently lacking in Maltese dogs and it is important to fill this gap as this breed is predisposed to myxomatous mitral valve disease, which is a volume overload disease. @*Objectives@#To establish the normal echocardiographic parameters for Maltese dogs. @*Methods@#In total, 23 healthy Maltese dogs were involved in this study. Blood pressure measurements, thoracic radiography, and complete transthoracic echocardiography were performed. The effects of body weight, age and sex were evaluated, and the correlations between weight and linear and volumetric dimensions were calculated by regression analysis. @*Results@#The mean vertebral heart size was 9.1 ± 0.4. Aside from the ejection fraction, fractional shortening, and the left atrial to aorta root ratio, all the other echocardiographic parameters were significantly correlated with weight. @*Conclusion@#This study describes normal echocardiographic parameters that may be useful in the echocardiographic evaluation of Maltese dogs.

A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation / Journal of the Korean Cancer Association, 대한암학회지

A 61-year-old male patient was simultaneously diagnosed with lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). The lung adenocarcinoma and IMT harbored two distinct types of ALK translocation, LOC101927285-ALK, and TPM3-ALK, respectively. The ALK Ventana showed strong positivity on both lesions. The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib. The tumors showed durable response however the left lung adenocarcinoma relapsed at 17th month post-crizotinib treatment. Tissue re-biopsy on the resistant tumor revealed an ALK exon 23 C1156Y missense mutation in addition to LOC101927285-ALK mutation. Further RNA-based sequence uncovered that the noncoding region rearrangement is the fusion mutation of EML4-ALK. The patient was therefore received alectinib, and the tumor exhibited partly response. Overall, it is very rare that two types of pulmonary tumors exist in one patient driven by two distinct ALK fusions, which emphasizes the necessity of gene sequencing in clinical decision-making and individualized therapy.

Echocardiographic parameters and indices in 23 healthy Maltese dogs

Background@#Echocardiography is a primary tool used by veterinarians to evaluate heart diseases. In recent years, various studies have targeted standard echocardiographic values for different breeds. Reference data are currently lacking in Maltese dogs and it is important to fill this gap as this breed is predisposed to myxomatous mitral valve disease, which is a volume overload disease. @*Objectives@#To establish the normal echocardiographic parameters for Maltese dogs. @*Methods@#In total, 23 healthy Maltese dogs were involved in this study. Blood pressure measurements, thoracic radiography, and complete transthoracic echocardiography were performed. The effects of body weight, age and sex were evaluated, and the correlations between weight and linear and volumetric dimensions were calculated by regression analysis. @*Results@#The mean vertebral heart size was 9.1 ± 0.4. Aside from the ejection fraction, fractional shortening, and the left atrial to aorta root ratio, all the other echocardiographic parameters were significantly correlated with weight. @*Conclusion@#This study describes normal echocardiographic parameters that may be useful in the echocardiographic evaluation of Maltese dogs.

A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation / Journal of the Korean Cancer Association, 대한암학회지

A 61-year-old male patient was simultaneously diagnosed with lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). The lung adenocarcinoma and IMT harbored two distinct types of ALK translocation, LOC101927285-ALK, and TPM3-ALK, respectively. The ALK Ventana showed strong positivity on both lesions. The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib. The tumors showed durable response however the left lung adenocarcinoma relapsed at 17th month post-crizotinib treatment. Tissue re-biopsy on the resistant tumor revealed an ALK exon 23 C1156Y missense mutation in addition to LOC101927285-ALK mutation. Further RNA-based sequence uncovered that the noncoding region rearrangement is the fusion mutation of EML4-ALK. The patient was therefore received alectinib, and the tumor exhibited partly response. Overall, it is very rare that two types of pulmonary tumors exist in one patient driven by two distinct ALK fusions, which emphasizes the necessity of gene sequencing in clinical decision-making and individualized therapy.

[Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in treatment of rheumatoid arthritis].

Tripterygium wilfordii Hook.f.(TwHF) is one of the most effective traditional Chinese herbal medicines against rheumatoid arthritis. As the representative agents of TwHF, Tripterygium Glycoside Tablets(TGT) and Tripterygium wilfordii Tablets(TWT) were included as Class A drugs in the 2019 edition of Medicine Catalogue for National Basic Medical Insurance, Injury Insurance and Maternity Insurance, and TGT was also included in 2018 edition of National Essential Drug List and 2015 edition of Chinese Pharmacopoeia. However, it is difficult to grasp the specific clinical applications of TGT and TWT. Side effects occur from time to time. The curative effect is uneven in patients. And the package inserts of TGT and TWT are not described in details. In order to standardize the clinical application of Tripterygium wilfordii preparations, 38 authoritative units and 48 well-known experts in rheumatoid immunology clinical department, drug supervision and management, pharmacy and evidence-based medicine research fields jointly developed Tripterygium Glycoside Tablets and Tripterygium wilfordii Tablets Medication Guide for reference in clinical application, teaching and scientific research. The guideline followed the "evidence-based, consensus-assisted and experience-based" principles to form "recommendations" for the evidence supported ones, and form "consensus suggestions" for those without evidence support by using nominal group method. In this way, the medication recommendations on function, usage and dosage, drug combinations, precautions, efficacy, safety and other aspects of TGT and TWT can be provided. The application of this Guide will help to avoid or reduce the adverse reactions of T. wilfordii preparations, enhance the efficacy and reduce the cost of medicine, with certain demonstration and promotion values to improve the rational use level of traditional Chinese medicine.

[Editorial explanation for Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in treatment of rheumatoid arthritis].

Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the treatment of rheumatoid arthritis(T/CACM 1337-2020) was approved on June, 2020 by the Standardization Office of Chinese Association of Chinese Medicine. Our group developed this guideline for the clinical application of Tripterygium Glycosides/Tripterygium wilfordii Tablets according to the manual for the clinical experts consensus of Chinese patent medicine from January, 2018, when this project was approved by Chinese Association of Chinese Medicine. In this article, the detailed information on our compilation process was provided, in order to facilitate the understanding and the application of the guideline, as well as provide reference for the development of clinical practice guideline for other Chinese patent medicine.

Critical review of multimorbidity outcome measures suitable for low-income and middle-income country settings: perspectives from the Global Alliance for Chronic Diseases (GACD) researchers.

OBJECTIVES: There is growing recognition around the importance of multimorbidity in low-income and middle-income country (LMIC) settings, and specifically the need for pragmatic intervention studies to reduce the risk of developing multimorbidity, and of mitigating the complications and progression of multimorbidity in LMICs. One of many challenges in completing such research has been the selection of appropriate outcomes measures. A 2018 Delphi exercise to develop a core-outcome set for multimorbidity research did not specifically address the challenges of multimorbidity in LMICs where the global burden is greatest, patterns of disease often differ and health systems are frequently fragmented. We, therefore, aimed to summarise and critically review outcome measures suitable for studies investigating mitigation of multimorbidity in LMIC settings. SETTING: LMIC. PARTICIPANTS: People with multimorbidity. OUTCOME MEASURES: Identification of all outcome measures. RESULTS: We present a critical review of outcome measures across eight domains: mortality, quality of life, function, health economics, healthcare access and utilisation, treatment burden, measures of 'Healthy Living' and self-efficacy and social functioning. CONCLUSIONS: Studies in multimorbidity are necessarily diverse and thus different outcome measures will be appropriate for different study designs. Presenting the diversity of outcome measures across domains should provide a useful summary for researchers, encourage the use of multiple domains in multimorbidity research, and provoke debate and progress in the field.

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women.

BACKGROUND: The Uygur is the fifth most populous ethnic group in China. Compared to other Chinese population, cervical cancer in them had high incidence, and HPV infection also was particular. Their HPV integration situation has never been reported. We aimed to investigate the integration situation of 20 subtypes of HPV gene into host cell genome in Chinese Uygur cervical cancer patients; meanwhile, we explored the influence of gene integration on PD-L1 expression. METHODS: 40 frozen Chinese Uygur cervical cancer specimens with positive HPV infection were obtained from the cancer prevention and treatment institute of Tumor Hospital Affiliated to Xinjiang Medical University. The integration situation of HPV gene into host cell genome was detected by Agilent SureSelect™ Target Enrichment Chip and Next-Generation Sequencing. The related genes were analyzed by GO functional annotation and KEGG pathway enrichment. The expression levels of PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Meanwhile, the relationship between PD-L1 levels in cancer cells and gene integration were analyzed. RESULTS: The HPV multiple infection rate by HIVID was as high as 92.5%, much higher than 35.0% by the commercial kit (P < 0.05). There were 13423 integration events in 40 specimens, involving 6867 human genes. These integration events were distributed on all human chromosomes, and chromosome 19 had the excessive concentration phenomenon of integration events. There were some integration hotspots in human genome such as PPP1R37, HECW2, EMBP1, ANKRD50, SPTBN4, LINC00895, LYRM4-AS1, LINC00374, RBFOX1, CSMD1, CDH13, and KLHL4. Insertion breakpoints can be found in all gene regions of the HPV genome. The actual observation of the integration times of E1 and E6 was much higher than the expected value, while the actual observation times of E5 were much lower than the expected value. The result of GO functional analysis showed that binding molecular function and cellular process biological process were the main ways to influence the cell biological behavior of HPV gene integration. The enrichment pathway analysis of KEGG showed that pathways in cancer were the most important enrichment pathways involved in the genomic integration of HPV. The positive PD-L1 rate was 62.5%. Logistic regression analysis showed that 9p24.1 existing integration sites and the number of all gene integration were risk factors for PD-L1 expression (odds ratio 17.313 and 1.012; 95% confidence interval 1.691-177.213 and 1.001-1.023). Conclusions and Relevance. Most high-frequency sites of HPV integration in Chinese Uygur cervical cancer are related to cancer progression, and the gene integration hotspots may be potential HPV carcinogenic targets. The problem of multiple HPV infection in Chinese Uygur cervical cancer patients should be paid attention. L1 and E6 genes are inapposite as the target gene of commercial HPV type detection kit, because of high-frequency breakpoints in these genes. The gene integration especially the integration existing on 9p24.1 could affect the expression level of PD-L1.