The outbreak and spread of coronavirus disease 2019 (COVID-19) highlighted the importance and urgency of the research and development of therapeutic drugs. Very early into the COVID-19 pandemic, China has begun developing drugs, with some notable progress. Herein, we summarizes the anti-COVID-19 drugs and promising drug candidates originally developed and researched in China. Furthermore, we discussed the developmental prospects, mechanisms of action, and advantages and disadvantages of the anti-COVID-19 drugs in development, with the aim to contribute to the rational use of drugs in COVID-19 treatment and more effective development of new drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the variants. Neutralizing antibody is an effective approach to overcome COVID-19. However, drug resistance induced by rapid virus mutation will likely to challenge neutralizing antibodies. Taking into account current epidemic trends, small molecule drugs have a crucial role in fighting COVID-19 due to their significant advantage of convenient administration and affordable and broad-spectrum. Traditional Chinese medicines, including natural products and traditional Chinese medicine prescriptions, contribute to the treatment of COVID-19 due to their unique mechanism of action. Currently, the research and development of Chinese anti-COVID-19 drugs have led to some promising achievements, thus prompting us to expect even more rapidly available solutions.

Objective:To analyze and summarize the clinical manifestations, imaging and colonoscopy characteristics, treatment and prognosis of idiopathic mesenteric phlebosclerosis(IMP), so as to raise clinicians' awareness of this rare disease.Methods:One case of IMP admitted into the Department of Gastroenterology, Beijing Hospital, was reported.The patient was admitted primarily due to abdominal pain, distension, and obstructed defecation and flatulence for 3 months, and recurrent vomiting for 2 days.Combining the patient's medical history, symptoms, physical signs, imaging and colonoscopy results, IMP was suspected to be the most likely cause for incomplete intestinal obstruction in this case.The literatures on IMP published before April 2021, including case reports, reviews and articles, were collected and analyzed.Based upon information mentioned above, the epidemiological characteristics, pathogenesis, clinical manifestations, diagnosis, treatment and prognosis of IMP were systematically reviewed.Results:A total of 206 cases of idiopathic mesenteric vein sclerosing enteritis had been reported up to April 2021 in the literature, with a male to female ratio of about 2.75∶1.Age was clearly mentioned in 111 case reports, with a median age of 59 years and 36 patients(32.4%)≥65 years old.Common clinical manifestations include abdominal pain, distension, diarrhea, hematochezia, nausea and vomiting, obstructed defecation and flatulence, among others.The lesion is usually at the right side of the colon, including the cecum, ascending colon and transverse colon, with the ascending colon as the most commonly involved site.Imaging characteristics include linear, serrated or tortuous calcification of vessels inside the involved colon segments and adjacent mesenterium, edema and thickening of the intestinal wall, and reactive hyperplasia of lymph nodes, etc.Endoscopic features include edema and thickening of the intestinal wall, discoloration of the mucosa, and tortuous and dilated submucosal vessels.Complications include intestinal obstruction, perforation and necrosis.In most cases, symptoms subside after patients stop taking herbal medicines and go through conservative treatment for microcirculation improvement, anti-inflammation, anti-coagulation, anti-infection, etc.Overall, the prognosis of IMP is satisfactory.Conclusions:IMP is a type of non-obstructive, non-thrombotic and non-inflammatory mesenteric phlebosclerosis that causes intestinal ischemia.The pathogenesis of the disease is still unclear.Combination of characteristic clinical manifestations, imaging especially CT findings, endoscopic and histopathological examinations will help the diagnosis of IMP.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

Objective:To evaluate the psychological pain of patients with head and neck cancer aged ≥60 years old before and after intensity-modulated radiotherapy (IMRT).Methods:Distress Thermometer (DT)(Chinese version) was used to investigate the degree and problems of psychological pain before and after IMRT for 85 elderly patients with head and neck cancer. The results before and after IMRT were compared by paired t-test. Relevant factors were identified by Logistic regression analysis. Results:The median age in the cohort was 66 years old (60-85 years old). The incidence rates of psychological pain were 73% and 87% before and after IMRT ( P<0.001). The corresponding incidence rates of severe distress were 6% and 34%( P<0.001). The main distress problems before IMRT were memory loss/attention deficit, worry, oral pain, economic problems, stress, sleep problems, and dry nose. The significantly-increased distress problems after IMRT were oral pain, constipation, eating, nausea, and dry nose. Logistic regression analysis showed gender ( OR=5.520, 95% CI 1.437-21.212, P=0.013), pre-treatment PG-SGA score ( OR=1.220, 95% CI 1.048-1.421, P=0.010) and medical insurance ( OR=0.230, 95% CI 0.053-0.995, P=0.049) were the relevant factors of the severe psychological distress before IMRT. Occupation ( OR=2.286, 95% CI 1.291-4.050, P=0.005) and medical insurance ( OR=0.089, 95% CI 0.029-0.276, P<0.001) were the relevant factors of severe psychological distress after IMRT. Conclusion:The incidence rate of distress is high in elderly patients with head and neck cancer before IMRT, which can be aggravated after IMRT, primarily the treatment-related physical pain problems.

Objective:To investigated the clinical, biochemical, and immunohistological characteristics of patients with aldosterone producing adenoma(APA)and different gene mutations.Methods:The clinical and biochemical data of 206 patients with APA who received unilateral adrenalectomy were collected. Sanger sequencing was used to identify the mutation in the hot-point of KCNJ5 and other genes. The tumor samples were stained by 11β-hydroxylase(CYP11B1)and aldosterone synthase(CYP11B2), which was quantified by McCarty′s H-score system.Results:The gene mutations were identified in 166 out of 206(80.6%)patients with APA, of which 158 cases were KCNJ5 mutation, 2 ATP1A1 mutation, 5 ATP2B3 mutation, and 1 CTNNB1 mutation. Age, duration of hypertension, and serum potassium in APA patients with genetic mutant were significantly lower than those without genetic mutation( P<0.05) while the proportion of female, systolic blood pressure, diastolic blood pressure, aldosterone/renin ratio(ARR), and plasma aldosterone concentration(PAC)post saline infusion test(SIT)were significantly higher( P<0.05). Subgroup analysis showed that age, duration of hypertension, systolic blood pressure, and proportion of left ventricular hypertrophy in APA patients with ATP1A1 and ATP2B3 mutations were significantly higher than those with KCNJ5 mutation( P<0.05)while the PAC post SIT and tumor diameter were significantly lower( P<0.05). The positive rates of CYP11B2 in APA with different mutations were not significantly different. The H-score of CYP11B1 was significantly higher [160.0(127.5, 193.5) vs 80.0(27.5, 152.3), P=0.020] and the H-score of CYP11B2 was significantly lower [155.0(123.0, 190.0) vs 240.0(140.0, 270.0), P<0.01] in APA with KCNJ5 mutation compared with those with ATPase mutation. Conclusion:The types of genetic mutation are closely correlated with the clinical, biochemical, and immunohistological phenotypes in patients with APA.

Objective:To analyze the incidence and high-risk factors of lymph node metastasis in the retropharyngeal region of hypopharyngeal squamous cell carcinoma based on magnetic resonance imaging (MRI), aiming to guide the delineation of clinical target area.Methods:Clinical data of patients who were pathologically diagnosed with hypopharyngeal carcinoma from January 2012 to September 2018 in our center were retrospectively analyzed. All patients received head and neck MRI before treatment. The diagnosis of lymph node metastasis and the delineation of primary gross target volume (GTV p) and lymph nodes target volume (GTV nd) were determined by all the radiation oncologists in head and neck group through twice weekly general round discussion. The cut-off points of GTV p and GTV nd were defined by establishing the receiver operating characteristic curve. All patients were divided into the high GTV p, low GTV p and high GTV nd and low GTV nd groups. Chi-square test was used for univariate analysis and logistic regression was utilized for multivariate analysis to analyze the high-risk factors of patients with retropharyngeal lymph node metastasis. Results:A total of 326 patients were included in this study, 295 of whom were diagnosed with cervical lymph node metastasis, accounting for 90.5%. The most common involved area was Level Ⅱ a, followed by Level Ⅲ, Level Ⅱ b, Level IV, Level Ⅶ a (retropharyngeal), Level V a, and Level V b. The incidence of retropharyngeal lymph node metastasis was 21.5%, and the incidence was 53.1% in patients with primary tumor located in the posterior pharyngeal wall. Univariate and multivariate analyses showed that patients with tumor originated from the posterior pharyngeal wall ( P=0.002), bilateral cervical lymph node metastasis ( P=0.020), larger GTV p (greater than 47 cm 3, P=0.003), and larger GTV nd (greater than 22 cm 3, P=0.023) were significantly associated with the occurrence of retropharyngeal lymph node metastasis. Conclusions:The incidence of retropharyngeal lymph node metastasis is high in hypopharyngeal carcinoma, especially in patients with primary tumors in the posterior pharyngeal wall, bilateral cervical lymph node metastasis and larger primary burden. Therefore, for patients with these risk factors, it is highly recommended that the clinical target area should be delineated to include the retropharyngeal lymph node drainage area.

Objective:To evaluate the efficacy and safety of hypofractionated radiotherapy for lung metastases (LMs).Methods:From March 2007 to April 2019, 193 patients with 317 LMs including 124 male and 69 female admitted to our hospital were enrolled. The median age was 58 years old and the median KPS was 80. The primary tumors were mainly distributed in the lung (33.7%), colorectum (21.2%), head and neck (13.5%) and breast (10.9%), respectively. The clinical efficacy and side effects of hypofractionated radiotherapy for LMs were evaluated.Results:The median follow-up time was 59.9 months (95% CI: 55.1-64.6 months). Among 193 patients with 317 LMs, 90.7% of them were treated with 4D-CT, 69.4% for intensity-modulated radiation therapy (IMRT), 28.0% for volumetric-modulated arc therapy (VMAT) and 2.6% for tomotherapy (TOMO), respectively. The median gross tumor volume (GTV) and planning target volume (PTV) were 5.0 cm 3(0.2-142.3 cm 3) and 12.0 cm 3(1.0-200.1 cm 3). The prescription dose regimen was 60 Gy in 4 to 15 fractions. The median dose for PTV was 60 Gy (45-70 Gy) and biological effective dose was 96 Gy (60-150 Gy), respectively. The 1-, 3-and 5-year local control rates (LCR) were 95.7%, 91.3% and 89.9%, respectively. The median time from primary cancer diagnosis to lung metastases was a prognostic factor for LCR ( P=0.027). The overall survival (OS) and progression-free survival (PFS) rates were 90.1%, 60.8%, 46.2%, and 54.3%, 30.3%, 19.9%, respectively. The median time from primary cancer diagnosis to lung metastases and extrapulmonary metastases was the prognostic factor for OS and PFS. No Grade 3 toxicities were seen. Conclusion:Image-guided hypofractionated precision radiotherapy is an efficacious and safe treatment for LMs.

Objective:To evaluate the efficacy and safety of comprehensive treatment based on radiotherapy for patients with leptomeningeal metastases (LM) in this prospective study.Methods:A total of 93 patients diagnosed with LM admitted to our hospital undergoing whole brain radiotherapy (WBRT) or craniospinal irradiation (CSI) with or without simultaneous boost from 2014 to 2017 were enrolled. The dynamic changes of clinical signs and symptoms, enhanced magnetic resonance imaging (MRI), cerebrospinal fluid cytology and liquid biopsy detection were recorded. The primary endpoint was overall survival (OS), the secondary endpoints were local control (LC), intracranial progress-free survival (IPFS), brain metastasis specific survival (BMSS) and toxicity.Results:The major primary disease was non-small cell lung cancer. The whole cohort received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60 Gy in 20 f for boost), focal radiation to LM, WBRT and CSI (40 Gy in 20 f or 50 Gy in 25 f for WBRT and 36 Gy in 20 f for CSI). For 20 patients, tumor cells were identified and intrathecal chemotherapy was performed. Sixty-three patients received target therapy. The median follow-up time was 33.8 months. The 1-year OS, LC and IPFS was 62.4%, 77.2% and 52.6%, respectively. The median survival time was 15.9 months, and the median BMSS was 42.2 months. Treatment-related grade 3-4 adverse events were rare and only 8 cases was observed to have grade 3 hematological toxicity.Conclusion:Reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted therapy can be well tolerated and prolong the survival time of LM patients.

Objective:To investigate the patterns of regional lymphatic spread and the value of elective neck treatment (ENT) in oral mucosal melanoma (OMM).Methods:In this retrospective analysis, 61 OMM patients with no distant metastasis treated in Cancer Hospital of Chinese Academy of Medical Sciences between 1984 and 2016 were recruitred. The regional lymph node distribution of cN+ disease, the value of ENT in cN 0 disease, the failure patterns and prognostic factors were retrospectively analyzed. Results:Overall, 55.7% of the patients were clinical/pathological cN+ . The most frequently involved locations were the level Ⅰ b (76%), followed by level Ⅱ and level Ⅲ. For cN 0 patients, the 5-year regional failure-free survival rate was 91.7% in patients who received at least ipsilateral level Ⅰ b-Ⅲ ENT and 52.4% in patients who did not receive at least ipsilateral level Ⅰ b-Ⅲ ENT ( P=0.036). The regional failure rate was 6% for patients treated with at least ipsilateral leve Ⅰ b-Ⅲ ENT, while in their counterparts who did not receive at least ipsilateral level Ⅰ b-Ⅲ ENT was 46%( P=0.035). For the regional failure pattern, the most frequently failure sites were level Ⅰ b (93%), level Ⅱ(50%) and level Ⅲ(36%). Conclusions:The cervical lymph node metastasis rate is relatively high in OMM patients. The pathway of regional LN spread follows a regular pattern. The most frequently involved regions for clinical/pathological cN+ and regional failure are both level Ⅰ b-Ⅲ. Elective treatment including at least ipsilateral level Ⅰ b-Ⅲ ENT should be recommended for OMM patients with cN 0.