Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

The performance evaluation of tertiary public hospitals is a major measure to promote the high-quality development of public hospitals and contribute to the construction of Healthy China.In advancing performance evalua-tion,public hospitals face various challenges,including differing policies and economic levels across provinces,a need to optimize the indicator system,and internal issues such as varied discipline structures,uneven emphasis on different factors,untimely internal performance linkage,and lagging informatization.Based on a systematic perspec-tive,it proposes countermeasures and suggestions such as strengthening policy coordination,optimizing the indica-tor system,enhancing top-level design,increasing employee awareness,intensifying compensation guidance,and accelerating informatization construction.

The performance evaluation of tertiary public hospitals is a major measure to promote the high-quality development of public hospitals and contribute to the construction of Healthy China.In advancing performance evalua-tion,public hospitals face various challenges,including differing policies and economic levels across provinces,a need to optimize the indicator system,and internal issues such as varied discipline structures,uneven emphasis on different factors,untimely internal performance linkage,and lagging informatization.Based on a systematic perspec-tive,it proposes countermeasures and suggestions such as strengthening policy coordination,optimizing the indica-tor system,enhancing top-level design,increasing employee awareness,intensifying compensation guidance,and accelerating informatization construction.

ObjectiveTo describe the epidemic characteristics of COVID-19 after policy adjustment from “Category B notifiable disease with category A management” to “Category B notifiable disease with category B management”， and to explore the protective effect of previous infection with SARS-CoV-2 on common symptoms of reinfection. MethodsHealthcare workers infected with SARS-CoV-2 in a grade A tertiary hospital in Shanghai were included in the study from December 4， 2022 to January 11， 2023. Data on demographic characteristics， clinical symptoms， medical history， and COVID-19 vaccination history were collected. We determined the epidemiological curve and characteristics， and then compared the difference in the severity of clinical symptoms between primary and reinfection subjects. ResultsA total of 2 704 cases were included in the study， of which 45 had reinfection， 605 （22.4%）were males， 608 （22.5%）were doctors， 1 275 （47.2%） were nurses， and 2 351 （86.9%） received ≥3 doses of COVID-19 vaccination. The average age of these healthcare workers was （34.9±9.1） years old. The number of cases with mild/moderate illness， asymptomatic infection， fever， headache， dry cough， expectoration， and chest tightness were 2 704 （100.0%）， 92 （3.4%）， 2 385 （88.2%）， 2 066 （76.4%）， 1 642 （60.7%）， 1 807 （66.8%）， and 439 （16.2%）， respectively. Reinfection was a protective factor for fever （OR=0.161， P<0.001）， headache （OR=0.320， P<0.001）， and peak body temperature （β=-0.446， P<0.001）. ConclusionFollowing the COVID-19 policy adjustment as a category B notifiable disease， healthcare workers at a grade A tertiary hospital in Shanghai predominantly experiences mild to moderate COVID-19 symptoms. Reinfection results in milder clinical manifestations， with a lower proportion of being asymptomatic.

The performance evaluation of tertiary public hospitals is a major measure to promote the high-quality development of public hospitals and contribute to the construction of Healthy China.In advancing performance evalua-tion,public hospitals face various challenges,including differing policies and economic levels across provinces,a need to optimize the indicator system,and internal issues such as varied discipline structures,uneven emphasis on different factors,untimely internal performance linkage,and lagging informatization.Based on a systematic perspec-tive,it proposes countermeasures and suggestions such as strengthening policy coordination,optimizing the indica-tor system,enhancing top-level design,increasing employee awareness,intensifying compensation guidance,and accelerating informatization construction.

The performance evaluation of tertiary public hospitals is a major measure to promote the high-quality development of public hospitals and contribute to the construction of Healthy China.In advancing performance evalua-tion,public hospitals face various challenges,including differing policies and economic levels across provinces,a need to optimize the indicator system,and internal issues such as varied discipline structures,uneven emphasis on different factors,untimely internal performance linkage,and lagging informatization.Based on a systematic perspec-tive,it proposes countermeasures and suggestions such as strengthening policy coordination,optimizing the indica-tor system,enhancing top-level design,increasing employee awareness,intensifying compensation guidance,and accelerating informatization construction.

The performance evaluation of tertiary public hospitals is a major measure to promote the high-quality development of public hospitals and contribute to the construction of Healthy China.In advancing performance evalua-tion,public hospitals face various challenges,including differing policies and economic levels across provinces,a need to optimize the indicator system,and internal issues such as varied discipline structures,uneven emphasis on different factors,untimely internal performance linkage,and lagging informatization.Based on a systematic perspec-tive,it proposes countermeasures and suggestions such as strengthening policy coordination,optimizing the indica-tor system,enhancing top-level design,increasing employee awareness,intensifying compensation guidance,and accelerating informatization construction.

The performance evaluation of tertiary public hospitals is a major measure to promote the high-quality development of public hospitals and contribute to the construction of Healthy China.In advancing performance evalua-tion,public hospitals face various challenges,including differing policies and economic levels across provinces,a need to optimize the indicator system,and internal issues such as varied discipline structures,uneven emphasis on different factors,untimely internal performance linkage,and lagging informatization.Based on a systematic perspec-tive,it proposes countermeasures and suggestions such as strengthening policy coordination,optimizing the indica-tor system,enhancing top-level design,increasing employee awareness,intensifying compensation guidance,and accelerating informatization construction.