Mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant to construct a rat discogenic low back pain model / 中国组织工程研究

BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.

Consideration on " Patient-Centered" Drug Development for Rare Diseases / 罕见病研究

The unmet clinical needs of patients with rare diseases persist. Many rare diseases lack effective treatments, and drug development for rare diseases faces greater challenges than that for common multiple diseases. In recent years, the concept of " patient-centered" drug development has been widely adopted. The Center for Drug Evaluation(CDE) of the National Medical Products Administration has successively issued a series of relevant guiding principles, such as the Technical Guidelines for the Implementation of Patient-Centered Clinical Trials, to promote a " patient-centered" drug development model. The implementation of the " patient-centered" approach in rare disease drug research and development, with a focus on patient perspectives and active engagement, can effectively facilitate a comprehensive understanding of rare diseases and patient needs among drug research and development enterprises, researchers, and regulatory agencies. This approach also enhances the accuracy and efficiency of rare disease drug research and development. The CDE will continue to prioritize the integration of the " patient-centered" concept into rare disease drug research and development, effectively enhance the involvement of rare patients in the drug research and development process, and leverage the guiding role of patients′ perspectives on drug research and development.

Application of Decentralized Clinical Trials in the Research and Development of Drugs for Rare Diseases / 罕见病研究

Clinical trials of drugs for rare diseases face special challenges such as a limited number of patients, difficult recruitment, long trial period, and frequent video interviews during the trial. Therefore, in the clinical operation of rare diseases, a decentralized clinical trials (DCT) model based on the " patient-centred" research and development concept is implemented. With the help of decentralized elements and digital health technology, the barriers of geographical restrictions can be overcome and subjects do not have to be limited to traditional clinical trial sites (hospitals/research centers), which can significantly reduce the burden on subjects, increase their representation, and obtain a wider range of scientific research data. To guide the industry′s scientific and standardized application of DCT in the research and development of drugs for rare diseases, the Center for Drug Evaluation of the National Medical Products Administration (NMPA) organized the stake holders to draft the Technical Guideline for the Application of Decentralized Clinical Trials in the Research and Development of Drugs for Rare Diseases. This guideline provides scientific recommendations for the development and implementation of DCT for rare disease drugs. It aims to solve the difficult and key problems during rare disease drug research and development, improve the efficiency and optimize patient experience. This article, combining the research and development concepts in the guideline, explains the current research and development thinking on the application of DCT in the research and development of rare disease drugs, with a view of providing reference for the industry.

Extracellular Acidification Impairs Macrophage Lipophagy Through ASIC1/RIP1 Pathway / 生物化学与生物物理进展

ObjectiveOur recent study has demonstrated that extracellular acidification promotes lipid accumulation in macrophages via the activation of acid sensing ion channel 1 (ASIC1), but the underlying mechanism remains unclear. This study aims to explore the effect of extracellular acidification on macrophage lipophagy and the underlying mechanism. MethodsRAW264.7 macrophages were incubated with 25 mg/Lox-LDL in a pH 6.5 culture medium for 24 h to build macrophage-derived foam cell models induced by extracellular acidification. Then, RAW264.7 macrophages were cultured in the acidic medium of pH 6.5 with or without PcTx-1 (ASIC1 specific blocker, 10 μg/L) or Nec-1 (RIP1 specific inhibitor, 20 μmol/L) for 24 h, intracellular lipid accumulation was observed by oil red O staining. The expressions of total ASIC1, plasma membrane ASIC1, RIP1, p-RIP1 Ser166, TFEB, p-TFEB Ser142, LC3 and p62 were measured by Western blot. The co-localization of lipids (indicated by Bodipy) with LC3II (autophagosomes) and LAMP1 (lysosomes) was analyzed by a confocal laser scanning microscopy, respectively. Morphological changes of lipophagy in the cells were observed by using transmission electron microscopy. ABCA1-mediated cholesterol efflux was determined by cholesterol fluorescence kits. ResultsCompared with pH 7.4+ox-LDL group, the intracellular lipid accumulation in the pH 6.5+ox-LDL group was significantly increased. Meanwhile, the expressions of plasma membrane ASIC1, p-RIP1 Ser166, p-TFEB Ser142, and p62 proteins were elevated significantly, while LC3II protein level and LC3II/LC3I ratio were decreased. Accordingly, compared with pH 7.4+ox-LDL group, the macrophage lipophagy of the pH 6.5+ox-LDL group was inhibited as indicated by the decreased localization of lipid droplets with LC3 and LAMP1, a decrease in the number of lipophagosomes as well as an increase in lipid droplets. Furthermore, ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from the macrophages of pH 6.5+ox-LDL group reduced dramatically. However, these above effects of extracellular acidification on RAW264.7 macrophages were abolished by PcTx-1 and Nec-1, respectively. ConclusionThese findings suggest extracellular acidification promotes the phosphorylation of TFEB at Ser142 via activating ASIC1/RIP1 pathway, thereby impeding lipophagy in RAW 264.7 macrophages, and that ASIC1 may be a new potential target for preventing aberrant lipid accumulation diseases including atherosclerosis.

Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi / 中国医学科学院学报

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

Quality evaluation of Indigo Naturalis based on multi-component quantification combined with chemometrics / 中国药房

OBJECTIVE To evaluate the quality of Indigo Naturalis， and to provide reference for the quality control of Indigo Naturalis. METHODS UPLC-MS/MS method was used to determine the contents of 6 indole alkaloids （indigo， indirubin， isatin， tryptanthrin， indole and indole-3-carboxaldehyde） in Indigo Naturalis from different origins. Cluster analysis， principal component analysis and partial least squares-discriminant analysis （PLS-DA） were used to evaluate the quality of Indigo Naturalis from different origins. RESULTS The contents of indigo， indirubin， isatin， tryptanthrin， indole and indole-3-carboxaldehyde in Indigo Naturalis from different origins were 20 320.83-26 585.01， 1 327.69-3 102.25， 141.69-894.50， 2.17-5.27， 2.14-5.93 and 1.69-4.34 μg/g， respectively. The Indigo Naturalis from different areas were clustered into two categories by cluster analysis. Samples S1， S2， S4， S6， S7， S9 and S10 were clustered into category Ⅰ， and samples S3， S5， S8， S11 and S12 were clustered into category Ⅱ. Indigo Naturalis from different origins was evaluated with 3 principal components. The results showed that category Ⅰ sample scored higher and had better quality， while category Ⅱ sample scored lower and had worse quality. PLS-DA showed that indigo， indirubin， tryptanthrin and isatin were the main substances that reflected the quality difference of Indigo Naturalis. CONCLUSIONS The quality of Indigo Naturalis from different origins is different， and the quality of Indigo Naturalis of different batches from the same area is not stable. The quality evaluation method of Indigo Naturalis established in this paper is stable and reliable， which can provide a basis for the quality control of Indigo Naturalis.

CIC-rearranged sarcoma: a clinicopathological analysis of four cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and differential diagnosis of CIC-rearranged sarcoma (CRS). Methods: Five CRSs of 4 patients (2 biopsies of pelvic cavity and lung metastasis from case 4) diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2019 to 2021. All cases were evaluated by clinical presentation, H&E, immunohistochemical staining and molecular analysis and the related literature was reviewed. Results: There were one male and three females, the age at diagnosis ranged from 18 to 58 (mean 42.5) years. Three cases were from the deep soft tissues of the trunk and one case from the skin of foot. Grossly, the tumor size ranged from 1 to 16 cm. Microscopically, the tumor was arranged in nodules or solid sheets. The tumor cells were typically round or ovoid, with occasional spindled or epithelioid morphology. The nuclei were round to ovoid with vesicular chromatin and prominent nucleoli. Mitotic figures were brisk (>10/10 HPF). Rhabdoid cells were seen in four of five cases. Myxoid change and hemorrhage were observed in all samples and two cases showed geographic necrosis. Immunohistochemically, CD99 was variably positive in all samples, while WT1 and TLE-1 were positive in four of five samples. Molecular analysis showed CIC-rearrangements in all cases. Two patients succumbed within 3 months. One had mediastinal metastasis 9 months after surgery. One underwent adjuvant chemotherapy and remained tumor-free 10 months after diagnosis. Conclusions: CIC-rearranged sarcoma is uncommon and shows aggressive clinical course with dismal prognosis. The morphological and immunohistochemical characteristics can largely overlap with a variety of sarcomas; hence, knowledge of this entity is vital to avoid potential diagnostic pitfalls. Definitive diagnosis requires molecular confirmation of CIC-gene rearrangement.

Spatial distribution characteristics of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020 / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the spatial distribution characteristics of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody, and to examine the correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, so as to provide insights into advanced schistosomiais control in the province.@*METHODS@#The epidemiological data of schistosomiasis in Hunan Province in 2020 were collected, including number of permanent residents in survey villages, number of advanced schistosomiasis patients, number of residents receiving serological tests and number of residents seropositive for anti-Schistosoma antibody, and the prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were descriptively analyzed. Village-based spatial distribution characteristics of prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were identified in Hunan Province in 2020, and the correlation between the revalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody was examined using Spearman correlation analysis.@*RESULTS@#The prevalence of advanced schistosomiasis was 0 to 2.72% and the seroprevalence of anti-Schistosoma antibody was 0 to 20.25% in 1 153 schistosomiasis-endemic villages in Hunan Province in 2020. Spatial clusters were identified in both the prevalence of advanced schistosomiasis (global Moran's I = 0.416, P < 0.01) and the seroprevalence of anti-Schistosoma antibody (global Moran's I = 0.711, P < 0.01) in Hunan Province. Local spatial autocorrelation analysis identified 98 schistosomiasis-endemic villages with high-high clusters of the prevalence of advanced schistosomiasis, 134 endemic villages with high-high clusters of the seroprevalence of anti-Schistosoma antibody and 36 endemic villages with high-high clusters of both the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province. In addition, spearman correlation analysis showed a positive correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody (rs = 0.235, P < 0.05).@*CONCLUSIONS@#There were spatial clusters of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, which were predominantly located in areas neighboring the Dongting Lake. These clusters should be given a high priority in the schistosomiasis control programs.

Technical specifications operation of manual lactation technique based on Delphi method / 国际中医中药杂志

We applied literature review and the Delphi method to develop technical operation of manual lactation technique. The databases and websites were systematically searched, such as UpToDate, the Cochrane Library, CNKI, VIP, Wanfang, and SinoMed. The evidence related to the technique was evaluated by Appraisal of Guidelines for Research and Evaluation (AGREE Ⅱ), and A Measure Tool to Assess Systematic Reviews 2 (AMSTAR 2). the included evidence was classified and summarized to form the preliminary draft of the technical operation specification. A total of 26 experts were selected to evaluate the draft, and some recommendations were deleted and modified according to the screening criteria and expert opinions, resulting in the final technical specifications for manual lactation technique applicable to health care professionals. The study included 4 guidelines, 5 expert consensus articles, 2 clinical decisions, and 3 systematic reviews, and the overall quality of the evidence was fair. A total of 26 questionnaires were collected in each of 2 rounds of expert consultation, with a 100% return rate and an overall authority coefficient of 0.91. The technical practice specification was formed in 11 aspects, including assessment content, indications, contraindications, operation methods, adverse events, and treatment methods, with a total of 50 recommendations. The technical operation specification is comprehensive, and the recommendations are clearly expressed, which is in line with the real clinical situation and can provide effective reference for the clinical practice of this technique.

The best evidence summary for appropriate techniques of traditional Chinese medicine nursing to relieve chemotherapy-induced nausea and vomiting / 中国实用护理杂志

Objective:To retrieve, evaluate, integrate the evidence of Traditional Chinese Medicine (TCM) nursing appropriate technology for chemotherapy-induced nausea and vomiting at home and abroad, and summarized the relevant best evidence to provide evidence-based basis practice for the clinical standard management of chemotherapy-induced nausea and vomiting and improved the treatment efficiency of patients' symptoms.Methods:The study evidence on TCM nursing appropriate technology for chemotherapy-induced nausea and vomiting systemically retrieved in the websites and databases,included13 guidelines and evidence summary websites, namely National Guideline Clearinghouse, New Zealand Guidelines Group, Medlive, etc; 6 Oncology Professional Association Websites, namely British Columbia Cancer Agency, Cancer Care Ontario, National Comprehensive Cancer Network, Oncology Nursing Society, European Society for Medical Oncology, American Society of Clinical Oncology;11 electronic databases, namely CNKI, VIP, WanFang, CBM, PubMed, Web of Science, Embase, etc; supplementary searched expert consensus and practice guidelines for cancer diagnosis and treatment including evidence-based decision-making, guidelines, evidence summaries, best/recommended practices, systematic reviews, expert consensus, and government documents. The literature retrieval period was from the database construction to January, 2023. The guidelines individually evaluated by 3 researchers, and the remaining literature independently evaluated by 2 researchers. The literature that met the criteria extracted and graded. Finally, the expert group integrated the evidence and summarized the evidence topics.Results:A total of 12 articles were involved, included 2guidelines,2 evidence summaries,3 expert consensuses, and 5 systematic reviews. Finally,4 evidence topics and 20 pieces of best evidence were formed, included applicable population, efficacy, safety and intervention measure .Conclusions:The best evidence of TCM nursing appropriate technology treatment of chemotherapy-induced nausea and vomiting provided evidence resources for clinical transformation, for traditional Chinese medicine and integrated Chinese and western medicine nursing group to provide clinical decision-making basis, and according to the principle of syndrome differentiation to form personalized practice scheme, effectively improved patients' symptoms, promote the recovery of patients.

NETO2 promotes melanoma progression via activation of the Ca2+/CaMKII signaling pathway / 医学前沿

Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca2+) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment.

Biallelic mutations in spermatogenesis and centriole-associated 1 like (SPATC1L) cause acephalic spermatozoa syndrome and male infertility / 亚洲男科学杂志(英文版)

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.

Summary of the best evidence for aromatherapy in alleviating chemotherapy related nausea and vomiting in patients with cancer / 中国实用护理杂志

Objective:To search and summarize the best evidence of aromatherapy in alleviating chemotherapy-related nausea and vomiting in cancer patients, so as to provide reference for nursing staff to implement symptom management.Methods:All evidences on the application of aromatherapy in the relief of chemotherapy-related nausea and vomiting in cancer patients were searched from the guideline collaboration network, professional association websites, and well-known databases at home and abroad from July 2011 to July 2021. The literature quality evaluation tool was used to evaluate the quality of the included literature, and extracted evidence from the literature that met the quality requirements.Results:Ten articles were included at last, including 2 clinical practice guidelines, 1 clinical decision, 2 expert consensus, 1 evidence to summarize, and 1 system evaluation. A total of 11 best evidences of aromatherapy to relieve chemotherapy-related nausea and vomiting were obtained. They were from five aspects: intervention population, aromatherapy practitioners, effectiveness, aromatherapy administration route and adverse reactions.Conclusions:The available evidence indicates that either essential oil aroma therapy or oral aroma therapy has a certain efficacy in alleviating chemotherapy-related nausea and vomiting, and more clinical studies, systematic reviews, and other evidences are still needed to be clarified in the future to promote the normative application of aroma therapy.

Intestinal microcirculation dysfunction in sepsis: pathophysiology, clinical monitoring, and therapeutic interventions / 世界急诊医学杂志（英文）

@#BACKGROUND: Intestinal microcirculation dysfunction is an important factor that causes poor prognosis in sepsis patients and is an important pathophysiological basis for the occurrence and development of sepsis. DATA RESOURCES: PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched from inception to August 1, 2021. The search was limited to the English language only. Two reviewers independently identified studies related to intestinal microcirculation dysfunction in sepsis. Exclusion criteria were duplicate articles according to multiple search criteria. RESULTS: Fifty articles were included, and most of them were animal studies. These studies reported pathogenesis, including endothelial dysfunction, leukocyte recruitment and adhesion, microthrombus formation, microcirculation hypoperfusion, and redistribution of intestinal wall blood flow. The monitoring methods of intestinal microcirculation were also diverse, including handheld microscopes, intravital microscopy (IVM), laser Doppler blood flow instruments, laser speckle contrast imaging, tissue reflectance spectrophotometry, biochemical markers of intestinal ischemia, and histopathological examination. In view of the related pathogenesis of intestinal microcirculation disorder in sepsis, existing studies also have different opinions on its treatment. CONCLUSIONS: Limited by monitoring, there are few clinical studies on intestinal microcirculation dysfunction in sepsis. Related research mainly focuses on basic research, but some progress has also been made. Therefore, this review may provide a reference for future research on intestinal microcirculation dysfunction in sepsis.

Consideration on the Research and Development of New Drugs for Rare Tumors / 中国肺癌杂志

In recent years, China's anti-tumor drugs has shown a continuous growth trend, and the activity of anti-tumor research and development in China accounts for a higher proportion in the world. However, further analysis of research and development hotspots show that the research and development of anti-tumor drugs is uneven among different tumor types. Due to the small number of the patients, it is difficult to conduct clinical trials, resulting in less drug development in the field of rare tumors. However, patients' treatment needs will also bring potential opportunities for pharmaceutical companies. The development of basic research and the discovery of new molecular tumor typing make "rare tumors" a dynamic concept. The scope of "rare tumors" may gradually expand with the precise development of treatment; or as the knowledge of tumors gradually develops from histocytology to the molecular level, It is possible that certain tumors with specific mutations can be combined into a group of non-rare "pan-tumors". Rare tumors are characterized by both rare diseases and tumors. Its drug research and development should not only meet the requirements of tumor drug research and development, but also adapt to the characteristics of rare diseases. Therefore, in the drug research and development, we can refer to the research and development principle of rare disease drugs, combine with the characteristics of tumor diseases, make full use of non-rare tumor clinical trials, make full use of scientific tools and exquisite trial design, and realize the promotion of the research and development of rare tumor drugs. This paper will summarize the thoughts in the review of new drugs in the field of rare tumors, in order to provide guidance for the industry.
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Considerations on Clinical Development and Regulatory of the Oversea License-in Anti-tumor Drugs / 中国肺癌杂志

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Correlation between postoperative decentration and tilt of aspherical intraocular lens implantation and visual quality / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the correlation between postoperative lens decentration and tilt and visual quality in eyes implanted with aspherical intraocular lens(IOL)by using a new anterior segment swept-source optical coherence tomography(OCT)CASIA2.METHODS: An observational study. A total of 90 eyes of 62 participants who underwent age-related cataract surgery at 1mo were included. Using CASIA2 by an experienced examiner, IOL tilt and decentration were obtained three consecutive times after mydriasis and the vector mean values were calculated. Double-pass optical quality analysis system(OQAS)and wavefront aberration instrument KR-1W were used for the visual quality measurements, including the total high-order aberration(tHOA), spherical aberration(SA), Coma, objective scatter index(OSI), modulation transfer function cut off frequency(MTF cut off)and Strehl ratio(SR)at 4 and 6mm pupil diameter.RESULTS: IOL decentration was positively correlated with SA(r=0.347, P=0.001)and OSI(r=0.343, P=0.002)at 4mm pupil diameter, and it was negatively correlated with MTF cut off(r=-0.244, P=0.032). There was no significant correlation between IOL decentration and tHOA, Coma and SR. IOL tilt was negatively correlated with MTF cut off(r=0.-345, P=0.002)and SR(r=-0.256, P=0.023)at 4mm pupil diameter, but it was not correlated with tHOA, SA, Coma and OSI. There were no significant correlations between the IOL decentration and tilt and tHOA, SA, Coma, MTF cut off and SR at 6mm pupil diameter.CONCLUSION: After aspherical IOL implantation in age-related cataract patients, IOL decentration was weakly correlated with SA at 4mm pupil diameter, while decentration and tilt were not significantly correlated with other higher-order aberrations. The decentration and tilt were weakly correlated with OSI value and MTF cut off value of the visual quality parameters. The results suggest that clinicians should pay more attention to higher-order aberrations and visual quality during precise cataract surgery.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

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.

Practice and exploration of the " 1+ 6+ N" medical alliance cooperation system of a hospital in Xinjiang / 中华医院管理杂志

Medical alliances constitute a vertical integration of regional medical resources, and an effective means to promote the tiered medical services. As one of the largest tertiary hospitals in Xinjiang, a hospital has gradually built a " 1+ 6+ N" medical alliance cooperative system fitting the geographical characteristics of Xinjiang since 2018. The system was based on the hospital, made county-level medical institutions as the hub, primary medical and health units as the focus, and telemedicine as the bridge. It turned a telemedicine service platform as the medium, integrating such service segments, as offline practices of experts like clinical teaching, ward rounds, surgical guidance and discipline construction, and as online practices like remote consultation, remote diagnosis, remote education, and remote new technology training among others. Then these segments were integrated into such cooperative models as the remote cooperative medical alliances, specialist-cooperative medical alliances, inter-department co-construction medical alliances, precision-based assistance medical alliances, urban medical group type of medical alliances, and " alliance-consortium" integrated development medical alliances. These practices enabled the expansion and primary support of high-quality medical resources. By June 2022, the hospital had established cooperation via medical alliances with 285 medical institutions at all levels. The implementation of this cooperation mechanism has effectively improved the medical service capacity, diagnosis and treatment capacity of difficult and critical diseases, diagnosis and treatment homogeneity and remote diagnosis capacity in the region, as well as the smooth and orderly progress of the tiered medical services and two-way referrals within a medical alliance.