An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries.In this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed.Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in China.In this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019.Information was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other reviews.As of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated.Among them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in phase-1.Most of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial protein.Overall,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China.Hopefully,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

“Blind men and an elephant”:The need for animals in research,drug safety studies,and understanding civilizational diseases

Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economically driven human migration,tourism-related activities,densely populated metropolitan areas,and local policies,humans will be affected by a multitude of novel disease-causing microorganisms and civilizational diseases.Despite disparities among countries,recent and planned changes in regulations concerning animal research and drug safety studies could have detrimental effects on both the animal research community and nations lacking sufficient social support systems.Based on existing scientific literature,I argue that we need animal research encompassing aspects such as animal development,behavior,drug safety studies,and for the understanding of future civilizational diseases.Depending on the nature of the research questions and local challenges,a suitable animal model organism should be made mandatory.

Research on Distributed System Course Under the Background of New Engineering

Distributed System Course is a professional computer course of Harbin Institute of Technology.With the guidance of the education strategy under the background of New Engineering,we adhere to the concept of cultivating diverse and innovative outstanding engineering and technology talents.This course conducts research on the teaching content,teaching mode,and evaluation system.It combines the traditional teaching mode with the online teaching mode,as well as problem-driven theories with practice,and adopts a diversified evaluation system.The research of the course has fully mobilized students’learning enthusiasm,improved teaching quality,and achieved significant teaching results.

Global trends in diabetic eye disease research from 2012 to 2021

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

Research progress on natural products against hepatocellular carcinoma

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

Research on the Teaching Reform and Practice of the Food Analysis Course Under the New Situation

With the development of society,the overall development of various industries in our country is unprecedentedly prosperous.However,various damaging industries with the sole goal of profit have emerged,significantly reducing people’s experience in basic needs such as food,clothing,housing,and transportation.Food analysis course is an essential primary subject established by colleges and universities to cultivate food quality and safety talents.In order to further ensure the food safety of society,this article mainly analyzes the teaching reform path of food analysis courses under the new situation.We hope the views in this article can provide guidelines for relevant workers.

Research Progress in FDA’s Focus Areas of Regulatory Science for Drugs and Suggestions for China

Objective To sort out the focus areas of FDA’s scientific supervision and to achieve corresponding results,so as to provide some suggestions for the scientific research and innovation of drug supervision in China.Methods In-depth research was carried out in the fields of safety evaluation tools,clinical trial innovation,new methods of product quality evaluation,information science and so on.Results and Conclusion The research foundation of drug supervision related technology in China is weak,and a systematic supervision system has not been formed.Learning from the scientific experience of drug supervision in the United States,we can promote the development of the focus areas of drug supervision in China.Besides,we should improve the standard management ability while perfecting the regulations and standards system.Lastly,we should establish a system for government and industry-university-research to realize the full-cycle supervision of drugs.

Opinion on pharmacology research and new drug development from precision medicine

Since President Obama announced the Precision Medicine Initiative from a national strategy perspective in his State of the Union address,precision medicine has rapidly become a world-wide hotspot and drawn global attention in the medical field.Precision medicine aims at applying genetic information of individual diseases to guide his or her diagnosis and treatment.

Analytic Hierarchy Process for Technological Risks in the Process of Innovative Drug Development in China

Objective To identify the critical risks in the process of innovative drug research and development,and to provide reference for improving the efficiency of innovative drug development and risk control in China.Methods Expert investigation and analytic hierarchy process were used to determine the weights of different risks.Results and Conclusion The research and analysis results showed that the risks at different stages of development had different effects on the success rate of drug development,among which the risk at the drug discovery stage influenced the most.In the drug discovery stage,inappropriate target selection had the greatest impact on the success rate of drug development.The lack of appropriate cell tissue or animal models had the greatest impact on the success rate of drug development from the discovery of a compound to the application for clinical trials.The difference in changes between nonclinical and clinical studies had the greatest impact on the success rate of drug development from early clinical studies to pivotal clinical studies.Incorrect dose selection had the greatest impact on the success rate of drug development from pivotal clinical studies to marketing authorization applications.The biggest impact from the marketing authorization application to the approval stage was inadequate communication with regulators.After investigating the weight of risk factors in the process of innovative drug development based on scientific methods,a new perspective for the risk control of new drug development and improving the research and development efficiency is provided.

Application Research of Earned Value Management in New Drug Research and Development Projects

Objective To help investors assess and control the costs of new drug development and reduce the risks of new drug development projects.Methods Cost analysis and financial forecasting were carried out with the integrated approach of earned value management.According to the principle of earned value management deviation analysis,the basic process of the new drug research and development project was combined with the hypothesis method from the research of Tufts Drug Development Research Center.Results and Conclusion If the project progress check was carried out in the clinical trial,the project costs were found overspent,the efficiency was low,the project progress was faster,and the resource investment was ahead.It is recommended that the adjustment should be made to reduce the input of resources,and increase the efficient key personnel to take the place of some less efficient staff.

The CAS System of New Drug Research and Its Key Results

The Chinese Academy of Science (CAS), the top national research hub for natural sciences, has always been committed itself to the national target of research and development (R&D) of new medicines. During the past several decades, a great number of R&D achievements have been attained. During the period from 1986 to 1999, for example, 135 pharmacutical projects won prizes of the CAS awards for natural sciences, inventions and S&T progress (roughly ac-

New Developments in Drug Therapy and Research of Cerebral Vasospasm

In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.

Research Progress of Transdermal Patches in Veterinary Drug Preparations

With the development of pharmaceutics and other disciplines theories and advanced technologies, the application of many new drug delivery systems has gradually increased in clinical veterinary. Among the many drug delivery systems, transdermal patch can maintain stable and effective plasma concentration and therapeutic effect in vivo for a long time after skin dressing delivery, which provides a safe and effective drug-delivery way for the therapy and prevention of some chronic diseases and partial analgesia in a simple and convenient way. Veterinary drug transdermal preparations have been developed both at home and abroad, and satisfactory results have been achieved in the experimental application. Based on the study of veterinary transdermal patches at home and abroad, this paper systematically describes the development and characteristics of transdermal patches, the factors affecting skin permeation and the evaluation this type of preparations in veterinary drugs.

New strategies against drug resistance to herpes simplex virus

Herpes simplex virus （HSV）, a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir （ACV） and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets （the DNA helicase/primase （H/P） complex）, new types of molecules （nature products） and new antiviral mechanisms （lethal mutagenesis of Janus-type nucleosides） to fight the drug resistance of HSV.

The brain-derived neurotrophic factor in neuronal plasticity and neuroregeneration: new pharmacological concepts for old and new drugs

Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.

New Progress of Oil and Gas Research in the Tonghua Area, East of the Songliao Basin

The Tonghua region in the east of the Songliao Basin is a high-risk and blank area of petroleum exploration. The unrevealed key problems including the growth of source rocks, hydrocarbon generation potential and oil and gas source and the low exploration degree have constrained the further study of petroleum geological conditions and exploration deployment. Based on outcrop and core observations, geological section survey, trench exploration, high-precision gravity and magnetism and geological survey wells, this work discussed the basic geological conditions, main hydrocarbon source rocks, hydrocarbon generation potential and the oil and gas source.

New drugs for the treatment of metastatic colorectal cancer

Colorectal cancer(CRC)represents one of the most frequent malignancies in terms of incidence and mortality,thus representing the third leading cause of cancer death worldwide.In the last decade,few drugs have enriched the treatment landscape of metastatic CRC and have significantly affected prognosis.Unlike other neoplasms,metastatic CRC patients who have exhausted treatment options often still maintain a good performance status.There are many challenges to increasing potential treatment options,notably a better understanding of disease biology and the mechanisms of resistance underlying cancer treatment failure.The development of new drugs for metastatic CRC certainly represents one of the most important challenges in medical oncology.This article discusses the main limitations in the development of new drugs and potential future scenarios.In particular,we addressed three questions:(1)The main limitations of targeted therapy in the treatment of metastatic CRC(mCRC);(2)New target armamentarium that could escape primary and secondary resistance and lead to more personalized mCRC therapy;and(3)Future directions.

A New Research about Pion Parton Distribution Function

A new fit of the pion parton distribution functions is provided. Only valence quark distributions are used at a low evolution scale and are evolved with the modified Dokshitzer- Gribov-Lipatov-Altarelli-Parisi equation which is briefly introduced in this work, and the sea quark and gluon distributions are only generated by the quantum chromodynamics processes. We find that the patton distributions can explain the pion-nucleon experiments data well, and it can also be compared with the data from the leading neutron data of experiments at HERA. The momentum distributions among the partons are discussed and our results are consistent with some models.