Characteristics and Research Progress of Traditional Chinese Medicine in Treatment of HER-2-Positive Breast Cancer： A Review / 中国实验方剂学杂志

Human epidermal growth factor receptor-2 （HER-2）-positive breast cancer has higher predilection to metastasize and invade other organs， leading to poor prognosis. The anti-HER-2 drugs， such as trastuzumab， pertuzumab， and trastuzumab emtansinehas， can remarkably prolong the disease free survival （DFS） of patients. However， frequent multidrug resistance， tumor recurrence and metastasis， and adverse reactions such as cardiotoxicity and gastrointestinal discomfort caused by adjuvant therapy are still challenges for the treatment of HER-2-positive breast cancer. The understanding of breast cancer in traditional Chinese medicine （TCM） has a long history. In thousands of years of inheritance and innovation， a standardized treatment system with TCM characteristics has been gradually formed， which shows unique advantages and significant curative effects in breast cancer treatment. The treatment principles of ''treatment based on syndrome differentiation''， ''treatment based on stages and types''， ''treatment according to individual conditions''， and ''treatment of different viscera and viscera based on the toxin and pathogen'' are closely related to the precise treatment concept. In view of the challenges in the treatment of HER-2-positive breast cancer， such as multidrug resistance， tumor recurrence and metastasis， cardiotoxicity， and gastrointestinal discomfort， this paper summarizes the characteristics of TCM in reversing the multidrug resistance， inhibiting tumor recurrence and metastasis， prolonging DFS， improving prognosis， reducing adverse reactions caused by adjuvant therapy， and improving the quality of life after breast cancer surgery according to the principles of reinforcing healthy Qi and eliminating pathogen， and treatment based on syndrome differentiation. This article is expected to serve as a reference for TCM treatment of HER-2 positive breast cancer.

Application of extracorporeal membrane oxygenation in early allograft dysfunction after heart transplantation / 器官移植

Objective To evaluate the effect of extracorporeal membrane oxygenation (ECMO) on early allograft dysfunction (EAD) after heart transplantation. Methods Clinical data of 614 heart transplant recipients were retrospectively analyzed. All recipients were divided into the ECMO group (n=43) and non-ECMO group (n=571) according to postoperative application of ECMO. In the ECMO group, the conditions of recipients undergoing ECMO after heart transplantation were summarized. Perioperative status and long-term prognosis of recipients were compared between two groups. Results Among 43 recipients undergoing ECMO, 17 cases underwent thoracotomy due to bleeding, 10 cases of infection, 4 cases of venous thrombosis of the lower limbs, and 1 case of stroke, respectively. Twenty-six recipients were recovered and discharged after successful weaning from ECMO, six died during ECMO support, six died after weaning from ECMO, five received retransplantation due to unsuccessful weaning from ECMO, and only one survived after retransplantation. Compared with the non-ECMO group, intraoperative cardiopulmonary bypass duration was significantly longer, the proportion of recipients requiring postoperative intra-aortic balloon pump (IABP), dialysis due to renal insufficiency, reoperation for hemostasis, infection, mechanical ventilation time≥96 h and tracheotomy was significantly higher, and the length of postoperative intensive care unit (ICU) stay was significantly longer in the ECMO group (all P < 0.05). The survival rate after discharge and 90-d survival rate in the ECMO group were 63% and 96%, significantly lower than 97% and 100% in the non-ECMO group (both P < 0.05). Survival analysis showed that the long-term survival rate in the ECMO group was significantly lower than that in the non-ECMO group (P < 0.05). After excluding the recipients who died within 90 d after heart transplantation, no significant difference was observed in the long-term survival rate (P > 0.05). Conclusions ECMO is an effective treatment of EAD after heart transplantation. The short-term survival rate of recipients using ECMO after heart transplantation is lower than that of those who do not use ECMO, and there is no significant difference in long-term survival of recipients surviving 90 d after heart transplantation.

Recent research on neurodevelopmental disorders in children / 中国当代儿科杂志

Neurodevelopmental disorders (NDDs) in children are a group of chronic developmental brain disorders caused by multiple genetic or acquired causes, including disorders of intellectual development, developmental speech or language disorders, autism spectrum disorders, developmental learning disorders, attention deficit hyperactivity disorder, tic disorders, and other neurodevelopmental disorders. With the improvement in the research level and the diagnosis and treatment techniques of NDDs, great progress has been made in the research on NDDs in children. This article reviews the research advances in NDDs, in order to further improve the breadth and depth of the understanding of NDDs in children among pediatricians.

Prognosis of traumatic spinal cord injury in children: Follow-up of 86 patients / 中华创伤杂志(英文版)

PURPOSE@#The long-term situation of children with spinal cord injury (SCI) was investigated, and suggestions for helping them better return to the society were provided.@*METHODS@#SCI patients less than 18 years old hospitalized in Beijing Boai Hospital from January 2011 to December 2020 were retrospectively analyzed. Information including motor function, complications, characteristic changes, self-care abilities, school attendance and social participation were collected by telephone interview and electronic questionnaire. All the answers were statistically analyzed.@*RESULTS@#A total of 86 cases were enrolled, 77 girls and 9 boys, with a median injury age of 6 years and 2 months. The follow-up time was 3-130 months. The main cause of trauma in these children was sport injury (66.3%), the thoracic spinal cord was involved the most (91.9%), and complete SCIs accounted for the majority (76.7%). In terms of complications, children with complete SCIs were more likely to have urinary incontinence, constipation and characteristic changes (p < 0.05); whereas the incomplete SCIs often have spasticity (p < 0.05). As to the daily living abilities, children with incomplete lumbar SCIs were more capable to accomplish personal hygiene, transfer, and bathing independently than those with complete injuries, or cervical/thoracic SCIs, respectively (p < 0.05). Moreover, children older than 9 years care more able to dress and transfer independently than the youngers (p < 0.05). Wheelchair users accounted for 84.9% and more than half of them were able to propel wheelchair independently, and those who move passively in wheelchairs were mostly introverted kids (p < 0.05). Almost all (93.8%) children with incomplete injuries were able to walk independently. Most (79.1%) children continued to attending school, and 41.9% participated in interest classes. Unfortunately, 67.4% of the children spent less time playing with their peers than before the injury.@*CONCLUSION@#SCIs impair physical structures and function of children, affect their independence in daily living, and restrict school attendance and social interaction. Comprehensive rehabilitation after injury is a systematic work. Medical staff and caregivers should not only pay attention to neurological function, but also help them improve self-care abilities. It is also important to balance rehabilitation training and school work and social participation.

Progress of decompression surgery for spinal metastases / 中国骨伤

The spine is the most common site of bone metastases from malignant tumors, with metastatic epidural spinal cord compression occurring in about 10% of patients with spinal metastases. Palliative radiotherapy and simple laminectomy and decompression have been the main treatments for metastatic spinal cord compression. The former is ineffective and delayed for radiation-insensitive tumors, and the latter often impairs spinal stability. With the continuous improvement of surgical techniques and instrumentation in recent years, the treatment model of spinal metastases has changed a lot. Decompression surgery underwent open decompression, separation surgery, minimally invasive surgery and laser interintermal thermal ablation decompression. However, no matter what kind of surgical plan is adopted, it should be assessed precisely according to the specific situation of the patient to minimize the risk of surgery as far as possible to ensure the smooth follow-up radiotherapy. This paper reviews the research progress of decompression for spinal metastases.

Research progress in separation surgery combined with stereotactic radiotherapy of spinal metastases / 中国骨伤

With the continuous improvement of cancer treatment, the survival of patients with spinal metastases has been significantly prolonged. Currently, the treatment of spinal metastases presents a trend of multi-mode. Clinical surgical methods include vertebral tumor resecting spinal canal decompression and internal fixation surgery, separation surgery, minimally invasive surgery and percutaneous ablation technology, etc. Radiotherapy techniques include traditional external radiation therapy, stereotactic radiotherapy and brachytherapy, etc. The risk of vertebral tumor resecting spinal canal decompression and internal fixation surgery, and the incidence of intraoperative and postoperative complications is high. The extension of postoperative recovery period may lead to delay of follow-up radiotherapy and other medical treatment, which has a serious impact on patients' survival and treatment confidence. However, the precision of traditional external radiation therapy is not high, and the limitation of tolerance of spinal cord makes it difficult to achieve the goal of controlling insensitive tumor. With the development of radiotherapy and surgical technology, stereotactic radiotherapy with higher accuracy and separation surgery with smaller surgical strike have become the focus of many clinical experts at present. This article reviews the progress of Hybrid treatment of separation surgery combined with stereotactic radiotherapy.

Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fsciculation with Muscle Ultrasound / 中国医学科学杂志(英文版)

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ2 = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

A Chinese Herb Prescription "Fang-gan Decoction" Protects Against Damage to Lung and Colon Epithelial Cells Caused by the SARS-CoV-2 Spike Protein by Regulating the TGF-β/Smad2/3 and NF-κB Pathways / 中国医学科学杂志(英文版)

Objective To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, "Fang-gan Decoction" (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.Methods Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p65, p-IκBα, p-Smad2/3, TGF-β1, Caspase3, and Bcl-2 was evaluated by Western blotting.Results FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-β/Smads and NF-κB signaling.Conclusion Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-β1/Smad pathways with tissue type specificity.

Textual research on Bambusae Concretio Silicea / 中国中药杂志

By studying various ancient texts such as herbal classics and medical literature from different eras, it was found that there were discrepancies in the records about Bambusae Concretio Silicea(Tian Zhu Huang). In order to establish an accurate foundation, this research was based on ancient herbal literature and combined with plant morphology and investigative studies to examine its earliest mentions in ancient texts, nomenclature, medicinal properties, indications, and quality assessment standards. In the early records, Bambusae Concretio Silicea was referred to by several different names, such as "Zhu Huang" "Tian Zhu Huang" "Zhu Gao" "Zhu Tang", and "Zhu Huang". The earliest known formal usage of the name "Tian Zhu Huang" was found in the book Ri Hua-zi's Materia Medica(Ri Hua Zi Ben Cao). Throughout various ancient texts, the earliest recorded information about Bambusae Concretio Silicea also appeared in Ri Hua-zi's Materia Medica, not in Materia Medica of Sichuan(Shu Ben Cao) or other ancient texts. Ri Hua-zi's Materia Medica provided relevant descriptions of its origin, medicinal properties, and indications, albeit with some errors due to limited knowledge. However, this has been a valuable starting point for future research on Bambusae Concretio Silicea and holds pioneering significance in forming a mature system. As the research delved deeper, the medicinal properties of Bambusae Concretio Silicea have been consistent since Ri Hua-zi's Materia Medica, and the understanding has gradually improved through years of clinical verification. During the investigation process, the authors found limited records on the quality evaluation of Bambusae Concretio Silicea in ancient texts. Although the information is scarce, it serves as a foundational basis for establishing corresponding quality grading standards for Bambusae Concretio Silicea in the future.

Recent Research Advance to Differentiate Portal Hypertension Associated with Primary Myelofibrosis and Cirrhosis --Review / 中国实验血液学杂志

Primary myelofibrosis (PMF) is easily confused with cirrhosis, due to its main clinical manifestations of splenomegaly and the blood cytopenia. This review focuses on clinical studies to identify primary myelofibrosis and cirrhosis related portal hypertension, to analyze the differences between the two diseases, in order to distinguish PMF and cirrhosis from the pathogenesis, clinical manifestations, laboratory examinations and treatment principles, and simultaneously improve clinicians' understanding of PMF, which is a reference for exploring the early screening or diagnostic indicators of PMF, also provides a clinical basis for the application of new targeted drugs such as ruxolitinib.

Research summary of chemical constituents and pharmacological effects of Panax notoginseng and predictive analysis on its Q-markers / 中国中药杂志

Panax notoginseng contains triterpene saponins, flavonoids, amino acids, polysaccharides, volatile oil and other active components, which have the effects of promoting blood circulation, stopping bleeding, removing blood stasis, etc. This study summarized the herbal research, chemical constituents and main pharmacological activities of P. notoginseng, and based on the theory of Q-markers of traditional Chinese medicine, predicted and analyzed the Q-markers of P. notoginseng from the aspects of plant kinship, efficacy, drug properties, measurability of chemical components, etc. It was found that ginsenosides Rg_1, Re, and Rb_1 with specific content ratio, ginsenosides Rb_2, Rb_3, Rc, Rd, Rh_2, and Rg_3, notoginseng R_1, dencichine and quercetin could be used as potential Q-markers of P. notoginseng, which facilitated the formulation of quality standards reflecting the efficacy of P. notoginseng.

Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.

Morbidity and risk factors of de novo malignancy after heart transplantation / 中华器官移植杂志

Objective:To explore the morbidity and risk factors of de novo malignancy after heart transplantation (HT).Methods:From June 2004 to August 2021, 995 patients undergoing HT were selected and followed up.The epidemiological characteristics, the morbidity of de novo malignancy (DNM) and its risk factors were examined.Kaplan-Meier survival analysis was performed for calculating the cumulative incidence and mortality of DNM.Log rank test was utilized for comparing the survival rate of each subgroup.Cox regression model was employed for examining the relationship between the included factors and the endpoint of DNM.Results:The median follow-up period was 6.36(3.64, 10.18) years.Thirty-six patients (3.6%) developed DNM during follow-up.Lung cancer accounted for 22.2%(8/36) of DNM while digestive system tumors accounted for 38.9% (including gastric cancer 6/36, 16.7%; liver cancer 3/36, 8.3%; colon cancer 2/36, 5.6%). The cumulative morbidity of DNM at Year 1/5/10/15 post-HT was 0.1%, 2.3%, 4.9% and 7.6% respectively.The median survival time of DNM recipients was 83.32 months.The mean survival time was significantly lower than those without DNM[(115.32±13.12) vs.(194.22±2.58), P<0.001]. The mortality of DNM recipients was around 6.57 folds higher ( HR=6.57, 95% CI: 4.06-10.64, P<0.01). Age was an independent risk factor for an occurrence of DNM.Hypertension and diabetes were also correlated with DNM. Conclusions:DNM after HT is associated with shorter survival time.And age is an independent risk factor for DNM after HT.

Analysis of risk factors for kidney dysfunction after heart transplantation and its impact onprognosis / 中华器官移植杂志

Objective:To summarize the incidence and long-term outcomes of postoperative renal dysfunction(RD) and explore the clinical predictors of postoperative RD to provide reference for preoperative evaluation and perioperative management of heart transplantation(HT).Methods:The relevant clinical data are retrospectively reviewed for 1 095 HT recipients.They are grouped into two groups of RD(352 cases)and non-RD(normal, 743 cases)according to whether or not RD occurred after HT.Two groups are compared to explore the clinical predictors associated with postoperative RD.For further examining the prognostic impact of perioperative renal dysfunction, the recipients are assigned into four groups based upon perioperative renal function.The long-term outcomes of four groups are compared.Results:The median follow-up period is 5.6 years.Among 352 RD patients (32.1%), there are new-onset(276 cases, 25.2%), occurring during postoperative hospitalization (99, 28.1%)and post-discharge until Year 1(111 cases, 31.5%).Compared with normal group, RD group have advanced age, greater body mass index(BMI), higher preoperative serum creatinine, longer cardiopulmonary bypass time, a higher ratio of male, diabetic history, preoperative RD, transplantation for previous graft failure, preoperative extracorporeal membrane oxygenerator(ECMO)and intra-aortic balloon pump(IABP); donors in this group had advanced age and higher ratio of male (all P<0.05).In terms of postoperative data, RD group had higher ratios of ECMO/IABP implantation, tracheostomy, infection, longer postoperative mechanical ventilation time, intensive care unit(ICU)stay and in-hospital stay than normal group( P<0.05).Long-term survival of patients with postoperative RD is significantly lower than that with postoperative normal kidney function( P<0.01).Long-term survival rate of patients with preoperative RD is significantly lower than that of those without preoperative RD, regardless of whether or not kidney function normalized postoperatively; long-term survival rate of patients with postoperative new-onset RD is significantly lower than that in those with normal kidney function( P<0.01).Advanced recipient age, higher BMI, existence of preoperative RD, postoperative cyclosporine dosing(versus tacrolimus)and cold ischemic time≥6 h are independent risk factors of RD post-HT. Conclusions:RD occurs predominantly within the first year post-HT.Advanced recipient age, higher BMI, existence of preoperative RD and cold ischemic time≥6 h are independent predictors of RD post-HT.The incidence of RD post-HT significantly affects perioperative and long-term survivals.

Analgesic effect of buccal acupuncture on patients after lumbar spinal fusion: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of buccal acupuncture on pain after lumbar spinal fusion.@*METHODS@#Sixty patients undergoing lumbar spinal fusion were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 1 case was eliminated). The patients in the control group were treated with routine anesthesia. On the basis of the control group, the patients in the observation group were treated with buccal acupuncture at bilateral back point, waist point, and sacral point for 30 min per treatment. The first acupuncture was given before anesthesia induction, and then once a day postoperation for two days, totally 3 treatments. The dosage of sufentanil, the number of remedial analgesia, and the incidence of nausea and vomiting within 48 h after surgery were compared between the two groups; rest and motion visual analogue scale (VAS) scores at 2 (T1), 8 (T2), 12 (T3), 24 (T4), and 48 (T5) h after surgery were observed; the quality of recovery-15 scale (QoR-15) at 24 and 48 h after surgery were evaluated.@*RESULTS@#The dosage of sufentanil and the number of remedial analgesia within 48 h after surgery in the observation group were lower than those in the control group (P<0.01). There was no significant statistically difference in rest and motion VAS scores between the two groups in T1, T2, T3, T4 and T5 (P>0.05). The QoR-15 scores in the observation group at 24 and 48 h after surgery were higher than those in the control group (P<0.01). The incidence of nausea in the observation group was lower than that in the control group (P<0.05).@*CONCLUSION@#Buccal acupuncture could reduce the amount of postoperative analgesic drugs of patients after lumbar spinal fusion, and promote early postoperative recovery.

Analysis of effect of preoperative renal insufficiency on clinical prognosis of heart transplant recipients / 器官移植

Objective To evaluate the effect of renal insufficiency before heart transplantation on perioperative death, complications and long-term survival, and to compare the differences between preoperative serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) in preoperative risk assessment. Methods Clinical data of 1 095 heart transplant recipients were retrospectively analyzed. According to preoperative Scr level, all recipients were divided into the Scr < 133 μmol/L(n=980), Scr 133-176 μmol/L (n=83) and Scr≥177 μmol/L groups (n=32). According to preoperative eGFR, all recipients were divided into eGFR≥90 mL/(min·1.73m2) (n=436), eGFR 60-89 mL/(min·1.73m2) (n=418) and eGFR < 60 mL/(min·1.73m2) groups (n=241). Clinical prognosis of postoperative renal function, perioperative and long-term outcomes of recipients were compared among different groups. The effect of eGFR and Scr level on renal function injury and long-term survival after heart transplantation was assessed. Results With the increase of preoperative Scr level, the proportion of recipients undergoing postoperative continuous renal replacement therapy (CRRT) was increased, the proportion of recipients receiving postoperative mechanical circulatory support was elevated, the incidence of postoperative complications was increased, the duration of mechanical ventilation and intensive care unit(ICU) stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). With the decrease of preoperative eGFR, the proportion of recipients receiving postoperative CRRT was increased, the proportion of recipients using postoperative intra-aortic balloon pump (IABP) was elevated, the duration of mechanical ventilation and ICU stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). Scr≥177 μmol/L was an independent risk factor for postoperative death [adjusted hazard ratio (HR) 3.64, 95% confidence interval (CI) 1.89-6.99, P < 0.01]. Among different groups classified by Scr and eGFR, the cumulative incidence rate of postoperative renal function injury and long-term survival rate were statistically significant among three groups (all P < 0.05). In patients with preoperative Scr < 133 μmol/L, the cumulative incidence rate of postoperative long-term renal function injury was significantly increased with the decrease of preoperative eGFR (P < 0.01). There was no significant difference in postoperative long-term survival rate among patients stratified by different eGFR (P > 0.05). Conclusions Renal insufficiency before heart transplantation is associated with poor perioperative and long-term prognosis. Preoperative Scr and eGFR are the independent risk factors for postoperative renal function injury. Scr yields low sensitivity in the assessment of preoperative renal function, whereas it has high accuracy in predicting perioperative death risk. And eGFR is a more sensitive parameter to evaluate preoperative renal function, which may identify early-stage renal functional abnormality and take effective measures during early stage to reduce adverse effect on prognosis.

Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

Colorectal cancer-derived exosomes and modulation KRAS signaling

Colorectal cancer (CRC) is one of the most common cancers worldwide and one of the main causes of cancer-associated mortality. At the period of diagnosis, metastases to other tissues will be present in around 30% of CRC individuals. Individuals with CRC continue to have a poor prognosis despite advances in medication. There is a growing body of literature that CRC develops as a result of the aggregation of various mutations in tumor oncogenes or suppressor genes and that diagnosing cancer in its initial phases may assist in increasing the overall lifespan of individuals with the illness. On the other hand, tumor cells may discharge exosomes in response to oncogenic mutations. By Inhibiting signaling pathways, including the Kirsten rat sarcoma virus (KRAS) mechanism, which is important in a variety of cell activities, exosomes have been shown to cause colorectal cancer in animal studies. The purpose of this review was to summarize the latest discoveries on the modulation of KRAS signaling by exosomes extracted from colorectal cancer. (AU)

Tongue Coating in COVID-19 Patients: A Case-Control Study

It has been suggested that COVID-19 patients have distinct tongue features, which may help to monitor the development of their condition. To determine if there was any specific tongue coating feature in COVID-19, this study investigated the difference in tongue coating between COVID-19 subjects and subjects with other acute inflammatory diseases characterized by fever. Tongue images taken with smartphones from three age-matched groups, namely, COVID group (n=92), non-COVID febrile group (n=92), and normal control group (n=92), were analyzed by two blinded raters according to a tongue coating scoring scheme, which assessed the levels of thick fur, slimy or greasy fur, discolored fur and composite index of tongue coating. Compared with control, significant increases in all coating indexes were found in the COVID group (P<0.001), as well as in the non-COVID febrile group (P<0.001). However, no difference was observed between COVID and non-COVID febrile groups for all coating indexes measured. In COVID-19 subjects, their scores of coating indexes had weak but significant correlations with certain inflammatory biomarkers, including WBC and neutrophil - lymphocyte ratio. It is concluded that COVID-19 subjects have pathological tongue coating patterns that are associated with inflammatory responses, and these coating patterns can help to indicate the direction of disease development.

SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level

Cardiac manifestations are commonly observed in COVID-19 patients and prominently contributed to overall mortality. Human myocardium could be infected by SARS-CoV-2, and human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are susceptible to SARS-CoV-2 infection. However, molecular mechanisms of SARS-CoV-2 gene-induced injury and dysfunction of human CMs remain elusive. Here, we find overexpression of three SARS-CoV-2 coding genes, Nsp6, Nsp8 and M, could globally compromise transcriptome of hPSC-CMs. Integrated transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with hPSC-CMs of Nsp6, Nsp8 or M overexpression identified concordantly activated genes enriched into apoptosis and immune/inflammation responses, whereas reduced genes related to heart contraction and functions. Further, Nsp6, Nsp8 or M overexpression induce prominent apoptosis and electrical dysfunctions of hPSC-CMs. Global interactome analysis find Nsp6, Nsp8 and M all interact with ATPase subunits, leading to significantly reduced cellular ATP level of hPSC-CMs. Finally, we find two FDA-approved drugs, ivermectin and meclizine, could enhance the ATP level, and ameliorate cell death and dysfunctions of hPSC-CMs overexpressing Nsp6, Nsp8 or M. Overall, we uncover the global detrimental impacts of SARS-CoV-2 genes Nsp6, Nsp8 and M on the whole transcriptome and interactome of hPSC-CMs, define the crucial role of ATP level reduced by SARS-CoV-2 genes in CM death and functional abnormalities, and explore the potentially pharmaceutical approaches to ameliorate SARS-CoV-2 genes-induced CM injury and abnormalities.