Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

Objective To discuss the clinical efficacy and safety of hepatic arterial infusion chemotherapy(HAIC)combined with carrelizumab and sorafenib in treating advanced hepatocellular carcinoma(HCC).Methods The clinical data of 36 HCC patients,who were admitted to the Affiliated Nantong Third Hospital of Nantong University of China to receive HAIC combined with carrelizumab and sorafenib from August 2019 to August 2020,were collected.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST),the objective response rate(ORR)and disease control rate(DCR)of the combination therapy were evaluated.The Common Terminology Criteria Adverse Events Version 5.0 developed by American National Cancer Institute was used to evaluate the clinical safety.Results After receiving 4 cycles of FOLFOX-HAIC,the ORR and DCR of the patients were 38.9％and 77.8％respectively.The patients were followed up for 30 months.The median progression-free survival(mPFS)was 306 days(95％CI:242.7-369.3),and the median overall survival(mOS)was 515 days(95％CI:2 482.5-547.5).After HAIC treatment,one patient was successfully changed to surgical operation.The overall incidence of adverse events were 100％.There were 9 adverse events(25％)above grade m,including severe abdominal pain(n=2,5.6％),nausea(n=1,2.8％),vomiting(n=1,2.8％),elevated alanine aminotransferase(n=3,8.3％),elevated aspartate aminotransferase(n=1,2.8％),and death due to pulmonary failure caused by severe immune-induced pneumonia(n=1,2.8％).Conclusion For the treatment of advanced HCC,HAIC combined with carrelizumab and sorafenib has better ORR and DCR with controllable safety,which provides a new option for the treatment of advanced HCC.However,studies with large sample size need to be conducted before its long-term survival benefit of patients can be further validated.

Occupational silicosis (hereinafter referred to as "silicosis") exhibited individual differences in disease susceptibility, with genetic factors playing a crucial role in its onset and progression. Cytokines, such as interleukin (IL)-1RA +2018T>C locus, tumor necrosis factor-α -308G>A and -238G>A locus, transforming growth factor (TGF)-β1 +915G>C locus, were related to the development of silicosis. However, relationship between IL-17F +7488A>G and TGF-β1 -509T>C locus with silicosis had shown inconsistent results across different studies. Regulatory proteins such as matrix metalloproteinase (MMP)-2 -735C>T locus, MMP-9 rs3918242 locus, heat shock protein (HSP) 70-1+190G>C locus, carboxypeptidase M rs12812500 locus, family sequence similarity gene 13A (FAM13A) rs2609255 locus, and desmoplakin rs2076304 locus were also related to the development of silicosis. The A allele of the non-coding RNA miRNA-4508 rs6576457 increased the risk of developing silicosis-related pulmonary fibrosis in dust-exposed workers. The polymorphism in the long non-coding RNA ADGRG3 rs1814521 was related to silicosis susceptibility. Additionally, six circular RNAs of small nucleolar RNA host gene 14 rs17115143 sequence might be potential biomarkers of silicosis. Human leukocyte antigen-DR (HLA-DR) genes demonstrated a dual role in both risk and protection against silicosis, while angiotensin I-converting enzyme (ACE) gene polymorphisms likely affected silicosis development by modulating serum ACE activity. However, the mechanisms by which certain genetic variations affected susceptibility to silicosis remain unclear. Prospective studies with large-scale samples combining genetics, epidemiology, bioinformatics, and biofunctional studies are needed to promote the development of biomarkers for silicosis susceptibility and disease course, and clinical therapies.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Pain is one of the most prevalent health problems. Current medications for pain are mainly anticonvulsants， tricyclic antidepressants， and opioidergic drugs. However， their therapeutic effectiveness is limited during application， and some even have severe side effects. In recent years， research on natural ingredients from Chinese herbal medicine has been extensively conducted for their analgesic activities. A series of natural ingredients represented by alkaloids， coumarins， flavonoids， and terpenoids have shown great analgesic activity， and further studies on their analgesic mechanism have found that most natural products have multi-target analgesic mechanisms. It can exert analgesic effects by blocking ion channels， regulating related receptors， or inducing anti-inflammatory or antioxidant effects. In addition， many traditional Chinese medicine （TCM） formulas have shown great analgesic ability after clinical application and have multiple complex analgesic mechanisms. The drug cloud （dCloud） theory can better describe the mechanisms， and it can represent the complete therapeutic spectrum of multi-target analgesics from two dimensions， namely the "direct efficacy" that directly inhibits pain signals and the "background efficacy" that targets the root causes of pain. The authors summarized the research progress of natural ingredients with analgesic effects found in Chinese herbal medicine so far， as well as the analgesic efficacy and potential mechanisms of TCM formulas with great analgesic effects in clinical applications， so as to provide a new basis for searching for new analgesic drugs from TCM.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Background/Aims: The aim of this study was to analyze the chronological changes in postoperative complications in surgical ulcerative colitis patients over the past decade in China and to investigate the potential parameters that contributed to the changes. Methods: Ulcerative colitis patients who underwent surgery during 2008–2017 were retrospectively enrolled from 13 hospitals in China. Postoperative complications were compared among different operation years. Risk factors for complications were identified by logistic regression analysis. Results: A total of 446 surgical ulcerative colitis patients were analyzed. Fewer short-term complications (24.8% vs. 41.0%, P=0.001) and more laparoscopic surgeries (66.4% vs. 25.0%, P<0.001) were found among patients who received surgery during 2014–2017 than 2008–2013. Logistic regression suggested that independent protective factors against short-term complications were a higher preoperative body mass index (odds ratio [OR], 0.870; 95% confidence interval [CI], 0.785–0.964; P=0.008), laparoscopic surgery (OR, 0.391; 95% CI, 0.217–0.705; P=0.002) and elective surgery (OR, 0.213; 95% CI, 0.067–0.675; P=0.009). The chronological decrease in short-term complications was associated with an increase in laparoscopic surgery. Conclusions Our data revealed a downward trend of short-term postoperative complications among surgical ulcerative colitis patients in China during the past decade, which may be due to the promotion of minimally invasive techniques among Chinese surgeons.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Berberine (BBR) as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities. However, it is unknown if BBR can be applied without abrogating the efforts of vaccination. Here we show that priming of CD8⁺ T cells in the presence of BBR lead to improved central memory formation (Tcm) with substantially reduced effector proliferation, primarily orchestrated through activation of AMPK and Stat5. Tcm derived from vaccinated mice fed with BBR were able to adoptively transfer protective immunity to naïve recipients. Vaccination of BBR-fed mice conferred better memory protection against infection without losing immediate effector efficacy, suggesting appreciable benefits from using BBR in vaccination. Thus, our study may help to lay the groundwork for mechanistic understanding of the immunomodulatory effects of natural products and their potential use as adjuvant that allows the design of novel vaccines with more desirable properties.