Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a PD-1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1:1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by 2 cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either 6 cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or 6 cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in experimental arm and 118 patients in control arm, with surgery performed in 92% and 83.9%, respectively. At data cutoff (July 11, 2023), the pCR rate were 39.8% (95% CI, 30.7 to 49.5) in experimental arm compared to 15.3% (95% CI, 9.3 to 23.0) in control arm (difference, 24.6%; odds ratio, 3.7; 95% CI, 2.0 to 6.9; p < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, grade ≥ 3 treatment-related adverse events were 29.2% and 27.2%. 3-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

[Prognostic factor analysis of patients with unresectablelung squamous cell carcinoma].

Objective: To investigate the prognostic factors associated with unresectable (stage Ⅲa-Ⅳ, according to the 7th edition of the AJCC cancer staging manual) lung squamous cell carcinoma. Methods: We retrospectively analyzed 350 patients with inoperable locally advanced, recurrent or metastatic lung squamous cell carcinoma who were admitted to the First Affiliated Hospital of Chinese Medical University from January 2005 to June 2018. The clinical pathological data, treatment and survival follow-up information of the patients were collected. Kaplan-Meier survival was used to compare the overall survival rate of different risk groups. Univariate analysis and multivariate Cox regression analysis were used to determine the independent prognostic factors. Results: A total of 350 patients were enrolled. The median overall survival (OS) of these patients was 16.7 months. Univariate analysis showed the stage, Eastern Cooperative Oncology Group(ECOG), first-line chemotherapy evaluation (RECIST version 1.1), radiation therapy, number of systemic chemotherapy lines, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), C reactive protein (CRP), lactate dehydrogenase (LDH), whether liver, brain, boneor metastasis were associated with the OS of patients with advanced lung squamous cell carcinoma (all P<0.05). Multivariate analysis showed that ECOG score (HR=1.855, 95% CI: 1.063-3.239, P=0.030), whether underwent lung resection (HR=0.476, 95%CI: 0.302-0.751, P=0.001), first-line chemotherapy evaluation [stable disease (SD): HR=0.293, 95%CI: 0.159-0.540, P<0.001; complete response (CR)+ partial response (PR): HR=0.223, 95%CI: 0.120-0.413, P<0.001], CRP (HR=1.715, 95% CI: 1.080-2.723, P=0.042), LDH (HR=1.116, 95%CI: 0.780-1.596, P=0.002) and CEA (HR=1.855, 95%CI: 1.361-2.528, P<0.001) before chemotherapy, liver metastasis (HR=2.453, 95%CI: 1.461-4.120, P=0.001) are independent prognostic factors for patients with unresectable lung squamous cell carcinoma. Conclusion: The ECOG score, surgical treatment history, first-line chemotherapy, LDH, CEA and CRP before chemotherapy, liver metastasis are independent prognostic factors for patients with advanced lung squamous cell carcinoma.

Exploring Northwest China's agricultural water-saving strategy: analysis of water use efficiency based on an SE-DEA model conducted in Xi'an, Shaanxi Province.

Worldwide, water scarcity threatens delivery of water to urban centers. Increasing water use efficiency (WUE) is often recommended to reduce water demand, especially in water-scarce areas. In this paper, agricultural water use efficiency (AWUE) is examined using the super-efficient data envelopment analysis (DEA) approach in Xi'an in Northwest China at a temporal and spatial level. The grey systems analysis technique was then adopted to identify the factors that influenced the efficiency differentials under the shortage of water resources. From the perspective of temporal scales, the AWUE increased year by year during 2004-2012, and the highest (2.05) was obtained in 2009. Additionally, the AWUE was the best in the urban area at the spatial scale. Moreover, the key influencing factors of the AWUE are the financial situations and agricultural water-saving technology. Finally, we identified several knowledge gaps and proposed water-saving strategies for increasing AWUE and reducing its water demand by: (1) improving irrigation practices (timing and amounts) based on compatible water-saving techniques; (2) maximizing regional WUE by managing water resources and allocation at regional scales as well as enhancing coordination among Chinese water governance institutes.

Monoclonal antibody-related drugs for cancer therapy.

Much progress has been made during the last few decades in the treatment of malignancies. Many types of cancer cells comprising the tumor mass carry molecular markers that are not expressed or are expressed at much lower levels in normal cells. These findings provide new leads to drug design and development of therapeutic strategies involving monoclonal antibodies (mAbs) or related antibody drugs to treat malignancies. This article reviews recent advances in this targeting approach with a focus on the evolution and current use of prospective antibody drugs as effective ways to treat cancer. Additionally, the development of prospective antibody-drug conjugates will also be briefly described.

Evidence-based research on traditional Japanese medicine, Kampo, in treatment of gastrointestinal cancer in Japan.

Gastrointestinal cancer is a great threat to human health in Japan. Conventional anticancer therapies including surgery, radiation, and chemotherapy are the main strategies and play important roles in curing this disease or extending the life of patients with these cancers. On the other hand, patients undergo great suffering induced by these treatments. Kampo, the Japanese traditional medicine, has been used in clinics to reduce side effects and to improve the quality of life of gastrointestinal cancer patients in Japan. In order to testify to the efficacy and safety of these Kampo medicines and to clarify the underlying mechanisms, a number of clinical and basic studies were implemented in the past several decades. These studies suggested the benefits of Kampo medicine as an adjuvant to conventional anti-cancer therapies in treating gastrointestinal cancer. Since the safety and efficacy as well as quality control of traditional medicine have long been focused worldwide, the development course of Kampo medicine may provide reference to other countries in the world.

c-Met: A potential therapeutic target for hepatocellular carcinoma.

The approval of receptor tyrosine kinase (RTK) targeted agent sorafenib as the first effective drug for the systemic treatment of advanced hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. A better understanding of HCC pathogenesis will lead to development of novel targeted treatments. As a typical member of the RTK family, c-Met represents an intriguing target for cancer therapy. The c-Met signaling pathway has been shown to be deregulated and to correlate with poor prognosis in a number of major human cancers. This review discusses the possibility of c-Met as a target in HCC treatment from the following respects: i) c-Met expression and activation profile in HCC, ii) relationship between c-Met and clinicopathologic state and prognosis of HCC, iii) role of c-Met signaling activity in HCC genesis and progression, and iv) strategy of c-Met pathway targeting therapy in HCC treatment.

Prospects for using pre-exposure prophylaxis to control the prevalence of HIV/AIDS in China.

Although important progress has been achieved in combating HIV/AIDs over the past 30 years, HIV/AIDs is still a serious threat to today's world. In China, figures on the incidence of this disease have painted a less than optimistic outlook. As the prevailing methods of preventing HIV/AIDS are all partially effective, novel and effective preventive interventions are needed in order to control the spread of the disease. Pre-exposure prophylaxis (PrEP) is one of the most promising prevention strategies and has garnered great attention worldwide. Current clinical trials on the efficacy and safety of this strategy have had some favorable results though major challenges around the world remain. Thus, China has taken an active part in the PrEP study to limit the prevalence of HIV/AIDS. This article describes the status of the PrEP study and discusses the opportunities and challenges encountered when implementing this strategy in China.

Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation.

BACKGROUND: Exosomes are nanometer-sized vesicles that are released by normal and neoplastic cells. Previous studies have focused on the interaction between tumour-derived exosomes and the immune system, as a consequence of immune suppression or enhancement. However, the effects of tumour-derived exosomes on tumour cells themselves have not been well studied. AIMS: To investigate the effects of gastric cancer exosomes on tumour cell proliferation and the possible mechanisms. METHODS: By serial centrifugation and sucrose gradient ultracentrifugation, we isolated and purified the exosomes from gastric cancer SGC7901 cells, then viewed them by electron microscopy. Cell proliferation was measured by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay. Protein expression was assayed by Western blotting. RESULTS: SGC7901-cell-derived exosomes promoted the proliferation of SGC7901 and BGC823 cells. The increase in proliferation induced by exosomes was accompanied by activation of Akt and extracellular-regulated protein kinase, and phosphoinositide 3-kinase or extracellular-regulated protein kinase inhibitor partially reversed the proliferative effect of exosomes. Moreover, the exosome-induced increase in activity of Akt and extracellular-regulated protein kinase coincided with decreased expression of the Casitas B-lineage lymphoma family of ubiquitin ligases. CONCLUSION: Gastric cancer exosomes promoted tumour cell proliferation, at least in part, by activation of PI3K/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinase pathways. The decreased expression of Casitas B-lineage lymphoma proteins might have contributed to the activation of Akt and extracellular-regulated protein kinase.

Dynamic of modernizing traditional Chinese medicine and the standards system for its development.

This article reviewed the process of Traditional Chinese Medicine's modernization on a global scale. This process is motivated by the potential need for traditional medicine as a result of health transitions and increasing drug R&D based on know-how from TCM. The established standards system for modern medicine serves as a basic model yet has limitations in terms of comprehensively evaluating TCM. Spurred by policy committments, research to provide supplements suited to TCM's features and principles is underway. Advanced and interdisciplinary technology and methodology is expected to play an essential role in TCM development.

Recent advances in P-glycoprotein-mediated multidrug resistance reversal mechanisms.

Expression of the multidrug resistance (MDR) phenotype is responsible for chemotherapy failure in numerous cancers. Overexpression of mdr1 gene-encoded permeability glycoprotein (P-gp) is known to play a pivotal role in the development of this phenotype. The role of P-gp has been proposed as an important goal in the design of chemotherapy strategies. However, modulation of P-gp activity by chemotherapy has limited possibilities because of toxicity and poor specificity. In this article, we review the latest advancements in different potential P-gp-mediated MDR reversal mechanisms as well as the methods of evaluating MDR reversal activity, which would be helpful in finding novel MDR reversal agents (or chemosensitizers).

China-Japan enhance joint research cooperation for drug discoveries and development: News from CJMWDDT 2007 in Jinan, China.

Viral hepatitis is currently a major global cause of morbidity and mortality. In some Asian countries like China and Japan, Hepatitis B and C in particular are the most common extremely infectious diseases and are likely to develop into liver cirrhosis. Furthermore, statistics indicate that patients with liver cirrhosis resulting from hepatitis B and C have an increased risk of developing hepatocellular carcinoma (HCC). Scientists have worked tirelessly to find curative therapeutic strategies to control chronic hepatitis and liver cirrhosis, accompanied by improvements in public health and living conditions. China's Shandong University and the University of Tokyo in Japan previously established a longterm cooperative relationship. Cooperative programs include co-training of postgraduates, exchanges of visiting scholars, academic symposia, and a bilateral international joint research program. Some substantive progress has been made as a result of bilateral endeavors. For instance, the Shandong University China-Japan Cooperation Center for Drug Discovery & Screening (SDU-DDSC) has enhanced to serve as an important platform for further close cooperation. At the same time, the International Advancement Center for Medicine & Health Research (IACMHR) - "Drug Discoveries and Therapeutics" and International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA) - "BioScience Trends" were established (Visit http://www.ddtjournal.com and http://www.biosciencetrends.com ). The first China-Japan conference on new drug discoveries and therapeutics (CJMWDDT 2007) was recently held in Jinan, China May 27-29, 2007, which provided opportunities for further communication and cooperation and increased knowledge of new drug research and clinical cures for hepatitis. Financially supported by the National Natural Science Foundation of China (NSFC) and the Japan Society for the Promotion of Science (JSPS), the conference covered a wide range of topics in different areas of chemical biology, phytochemistry, medicinal chemistry, and pharmacology and it resulted in informed and genial discussions of hepatitis cures that yielded fruitful results. The active involvement and participation by attendees gave the conference a congenial atmosphere. In the end, an agreement was reached to work together on new drug discovery and effective hepatitis therapeutic strategies, and some agreements have resulted in the creation of handover protocols. The CJMWDDT 2007 was a highly successful scientific event that strengthened and promoted extensive cooperation between China and Japan for the development of new pharmaceutical products and hepatitis cures.

GMP implementation in China: A double-edged sword for the pharmaceutical industry.

China's Good Manufacturing Practice (GMP) standards that mainly parallel WHO standards were made compulsory in 2004. However, GMP implementation had both positive as well as negative impacts on the pharmaceutical industry, with negatives including pharmaceutical companies suffering economic hardships, poor execution of GMP standards, and sequent health scares. This report briefly describes the problems with GMP implementation in China.

Regulation of epidermal growth factor receptor in human colon cancer cell lines by interferon alpha.

BACKGROUND AND AIM: The biology of growth factor receptor expression has implications for receptor specific cancer therapy. In this study, we examined: (a) regulation of epidermal growth factor receptor (EGFR) expression in a panel of 10 human colon cancer cell lines using interferon alpha (IFN-alpha); (b) ability of IFN-alpha to inhibit cell proliferation; and (c) sensitivity of IFN-alpha pretreated cells to EGF. METHODS: Cell proliferation was measured both by crystal violet colorimetric and clonogenic assays. Cell surface, intracellular, and/or total cell protein expression of EGFR was assessed by indirect immunofluorescence flow cytometry and/or fluorescein isothiocyanate (FITC)-EGF binding and internalisation flow cytometric assay. RESULTS: IFN-alpha treatment upregulated expression of cell surface EGFR in seven of 10 colon cancer cell lines within 16 hours, reaching a peak within 48-96 hours; this was accompanied by transient elevation of intracellular EGFR and marked growth inhibition. IFN-alpha treated cancer cells were still sensitive to EGF proliferative stimulation. CONCLUSIONS: Our results indicate that cytostatic concentrations of IFN-alpha can enhance cell surface and intracellular EGFR expression in a proportion of human colon cancer cells. The antiproliferative action of IFN-alpha could not block the signal transduction of the EGF-EGFR pathway. This may have clinical implications for improving treatment based on targeting of EGFR.

[Modeling of feeling institution in pilot structural model].

Objective. To improve a structural pilot model proposed by R. A. Hess, in which element of observation feeling institution was neglected. Method. Real simulation results showed that there was a blind region for small observation signal, and pilot made no response in this region. So we knew that the basic characteristics of the observation feeling institution were observation threshold and observation noise. A Neural Network (NN) receptor model was augmented in the structural pilot model to describe the characteristics of human observation feeling institution. Furthermore, using the augmented model, the affection of the pilot model on the characteristics of the closed-loop system of pilot and controlled element was studied. Result. The affection of NN perception on the closed-loop system was that the stable gain region of the human pilot was extended. Conclusion. The proposed model was reasonable for the element of human feeling institution.

[Detection and analysis of mycoplasma in 400 cases of genitourinary infection in Wuhan area].

Mycoplasmas were examined by cultured in the urogenital secreta and the midpieceurine from 400 cases (88 men and 312 women) of genitourinary infection and 119 cases (positive rate 29.75%) of genitourinary infection in Wuhan area. The positive rates of ureaplasma urealyticum (Uu) and mycoplasma hominis (Mh) were 24.75% and 8.75% respectively. The authors also studied the infection rates of Neisseria gonorrheae, fungus and trichomonad by cultures and microscopic findings. The positive rates of Neisseria gonorrheae, fungus and trichomonad were 14.50%, 13.50% and 4.50% respectively. Results showed that mycoplasma was one of the common pathogens causing genitourinary infection in Wuhan area.

Study of coordination equilibria in systems of coexisting mononuclear and polynuclear complexes by an isosbestic point-spectrophotometric method.

This paper reports a method for determining the stability constants of complexes in a system of coexisting mononuclear and polynuclear complexes based on analysis of dual isosbestic points. First it is necessary to determine the dissociation degrees of either of the two complexes concerned in two directions, and then their stability constants. With this method, the conditional constant can be evaluated by appropriate treatment and selection of the proper equations for solutions. For demonstration purposes the scandium/Xylenol Orange system was used to test the model and satisfactory results were obtained.