Stevens-Johnson syndrome and toxic epidermal necrolysis in Hong Kong.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong. METHODS: This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020. RESULTS: There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%). CONCLUSION: This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.

[Comparison of the latest cancer statistics, cancer epidemic trends and determinants between China and the United States].

Objective: To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States. Methods: A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF). Results: In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection. Conclusions: China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

[Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages].

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

Understanding the effects of mesenchymal stromal cell therapy for treating osteoarthritis using an in vitro co-culture model.

Osteoarthritis (OA) is a leading cause of chronic pain and disability, for which there is no cure. Mesenchymal stromal cells (MSCs) have been used in clinical trials for treating OA due to their unique ability to generate paracrine anti-inflammatory and trophic signals. Interestingly, these studies have shown mainly short-term effects of MSCs in improving pain and joint function, rather than sustained and consistent benefits. This may reflect a change or loss in the therapeutic effects of MSCs after intra-articular injection. The present study aimed to unravel the reasons behind the variable efficacy of MSC injections for OA using an in vitro co-culture model. Osteoarthritic human synovial fibroblasts (OA-HSFs) were co-cultured with MSCs to investigate their reciprocal effects on cell responses and whether a short-term exposure of OA cells to MSCs was sufficient for reducing their diseased characteristics in a sustained manner. Gene expression and histological analyses were performed. OA-HSFs exposed to MSCs showed short-term downregulation of inflammatory markers. However, the MSCs showed upregulation of inflammatory markers and impaired ability to undergo osteogenesis and chondrogenesis in the presence of OA-HSFs. Moreover, short-term exposure of OA-HSFs to MSCs was found to be insufficient for inducing sustained changes to their diseased behaviour. These findings suggested that MSCs may not provide long-term effects in correcting the OA joint environment due to them adopting the diseased phenotype of the surrounding tissues, which has important implications for the future development of effective stem-cell-based OA treatments with long-term therapeutic efficacy.

Implementation of ovarian tissue cryopreservation in Hong Kong.

INTRODUCTION: Worldwide, >130 babies have been born from ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation can improve quality of life among young female cancer survivors. Here, we assessed the feasibility of OTC and subsequent OTT in Hong Kong via xenografts in nude mice. METHODS: This pilot study was conducted in a university-affiliated tertiary hospital. Fifty-two ovarian tissues were collected from 12 patients aged 29 to 41 years during ovarian surgery, then engrafted into 34 nude mice. The efficacies of slow freezing and vitrification were directly compared. In Phase I, non-ovariectomised nude mice underwent ovarian tissue engraftment. In Phase II, ovariectomised nude mice underwent ovarian tissue engraftment, followed by gonadotrophin administration to promote folliculogenesis. Ovarian tissue viability was assessed by gross anatomical, histological, and immunohistochemical examinations before and after OTC. Follicular density and morphological integrity were also assessed. RESULTS: After OTC and OTT, grafted ovarian tissues remained viable in nude mice. Primordial follicles were observed in thawed and grafted ovarian tissues, indicating that the cryopreservation and transplantation protocols were both effective. The results were unaffected by gonadotrophin stimulation. CONCLUSION: This study demonstrated the feasibility of OTC in Hong Kong as well as primordial follicle viability after OTC and OTT in nude mice. Ovarian tissue cryopreservation is ideal for patients who cannot undergo the ovarian stimulation necessary for oocyte or embryo freezing as well as prepubertal girls (all ineligible for oocyte freezing). Our findings support the clinical implementation of OTC and subsequent OTT in Hong Kong.

[The influence of interaction between polygenic risk score and intestinal fungal microbiota on the risk of schizophrenia].

Objective: To investigate the effect of interaction between polygenic risk score (PRS) and intestinal fungal microbiota on the risk of Schizophrenia (SCH). Methods: A case-control study was carried out. Drug-naïve, first-episode SCH patients were selected from the Psychiatric Department of the First Affiliated Hospital of Zhengzhou University between October 2017 and October 2019. Meanwhile, healthy controls (HCs) were recruited from local communities through online advertisement or physical examination center. Intestinal fungal microbiota was characterized by the 18S rRNA sequencing platform. The association of fungal microbial dysbiosis (F_MD) index, α-diversity indices and PRS with SCH was detected by logistic regression analysis. Results: A total of 137 SCH patients (62 males and 75 females) and 76 HCs (31 males and 45 females) were included in the study. The age of SCH patients and HCs was (22.5±7.5) years and (22.8±2.3) years, respectively. The results of logistic regression analysis revealed that PRS (OR=1.111, 95%CI: 1.036-1.178, P=0.002) and the increase of F_MD index (OR=1.200, 95%CI: 1.124-1.281, P<0.001) were risk factors for developing SCH. The increase of fungal α-diversity Shannon (OR=0.813, 95%CI: 0.755-0.874, P<0.001) index, Simpson index (OR=0.218, 95%CI: 0.091-0.523, P<0.001) and abundance of key Aspergillus (OR=0.928, 95%CI: 0.864-0.996, P=0.040) decreased the risk of SCH. Aspergillus abundance was positively correlated with cognitive domains including working memory (r=0.280, P=0.001), verbal learning (r=0.253, P=0.003), reasoning and problem solving (r=0.191, P=0.028). Conclusion: The increase of PRS may increase the risk of SCH. The increase of fungal α-diversity indices and Aspergillus abundance may decrease the risk of SCH. The interaction between PRS and intestinal fungi (Shannon index, Simpson index and Aspergillus) is a related factor for the risk of SCH.

[Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients].

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

[Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years].

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.

[Retropharyngeal lymph node dissection in head and neck cancers treated with transoral robotic surgery].

Objective: To evaluate the indications, safety, feasibility, and surgical technique for patients with head and neck cancers undergoing transoral robotic retropharyngeal lymph node (RPLN) dissection. Methods: The current study enrolled 12 consecutive head and neck cancer patients (seven males and four females) who underwent transoral robotic RPLN dissection with the da Vinci surgical robotic system at the Sun Yat-sen University Cancer Center from May 2019 to July 2020. Seven patients were diagnosed as nasopharyngeal carcinoma with RPLN metastasis after initial treatments, 4 patients were diagnosed as thyroid carcinoma with RPLN metastasis after initial treatments, and one patient was diagnosed as oropharyngeal carcinoma with RPLN metastasis before initial treatments. The operation procedure and duration time, intraoperative blood loss volume and complications, nasogastric feeding tube dependence, tracheostomy dependence, postoperative complications, and hospitalization time were recorded and analyzed. Results: All patients were successfully treated by transoral robotic dissection of the metastatic RPLNs, none of which was converted to open surgery. RPLNs were completely resected in 10 patients, and partly resected in 2 patients (both were nasopharyngeal carcinoma patients). The mean number of RPLN dissected was 1.7. The operation duration time and intraoperative blood loss volume were (191.3±101.1) min and (150.0±86.6) ml, respectively. There was no severe intraoperative complication such as massive haemorrhage or adjacent organ injury during surgery. Nasogastric tube use was required in all patients with (17.1±10.6) days of dependence, while tracheotomy was performed in 8 patients with (11.6±10.7) days of dependence. The postoperative hospitalization stay was (8.5±5.7) days. Postoperative complications occurred in 4 patients, including 2 of retropharyngeal incision and 2 of dysphagia. During a follow-up of (6.5±5.1) months, disease-free progression was observed in all patients, 10 patients were disease-free survival and other 2 patients were survival with tumor burden. Conclusions: The transoral robotic RPLN dissection is safety and feasible. Compared with the traditional open surgical approach, it is less traumatic and safer, has fewer complications and good clinical application potentiality. The indications for transoral robotic RPLN dissection include thyroid carcinoma, oropharyngeal carcinoma, and some selected nasopharyngeal carcinoma and other head and neck cancers. Metastatic RPLNs from some nasopharyngeal carcinoma with incomplete capsule, unclear border and adhesion to the surrounding vessels are not suitable for transoral robotic RPLN dissection.

[Multivariate analysis of the effect of two liver resection methods on the survival outcome of patients with intrahepatic cholangiocarcinoma].

Objective: To investigate the effect of anatomical hepatectomy and non-anatomic hepatectomy in the treatment of elderly patients with intrahepatic cholangiocarcinoma (IHCC) and their impact on survival outcomes. Methods: In this study, a retrospective method was used to select elderly patients with IHCC who were surgically treated in Shangqiu First People's Hospital from April 2014 to April 2018, and were divided into anatomic resection group and non-anatomical resection group according to the surgical methods they received.The factors affecting the survival outcome of IHCC in the two liver resection methods were analyzed and compared, as well as the effects of liver cirrhosis rate, TNM stage, ascites rate, lymph node metastasis rate, and vascular invasion rate on survival. Results: A total of 181 cases were included in this study, including 87 cases in the anatomical resection group, with 54 males and 33 females, aged (71.4±5.2) years old;There were 94 cases in the non-anatomical resection group, including 49 males and 45 females, aged (70.8±4.8) years.The 3-year survival rate of the anatomical resection group was 41.4% (36/87), which was higher than that of the non-anatomical resection group (25.5% (24/94), the difference was statistically significant (P<0.05);The median survival time of the anatomic resection group was longer than that of the non-anatomical resection group, and the difference was statistically significant P<0.05;The patient's TNM stage was stage III [OR (95%CI): 2.168 (1.245-3.776)], lymph node metastasis [1.664 (1.087-2.545)], and vascular invasion [1.883 (1.167-3.038)] was an independent risk factor for death 3 years after surgery (P<0.05), The patient's anatomical liver resection was a protective factor for the 3-year follow-up survival (P<0.05). Conclusion: The postoperative survival of elderly patients with IHCC is affected by many factors, but anatomic liver resection is beneficial to prolong the survival time of patients.

[Initiation timing of veno-arterial extracorporeal membrane oxygenation].

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a salvage therapy for critical patients with refractory cardiogenic shock caused by various reasons. It can temporarily replace cardiopulmonary function, and rapidly improve hypoxemia, increase systemic oxygen content and remove carbon dioxide. Although the Extracorporeal Life Support Organization (ELSO) guideline proposed clear indication for VA-ECMO, the heterogeneity of cardiac pathogeny is large, so the clear timing of ECMO initiation is still vague. We discuss the timing of ECMO initiation for external cardiopulmonary resuscitation (ECPR) and cardiogenic shock which is caused by fulminant myocarditis, acute myocardial infarction, acute pulmonary embolism, acute right heart failure related to lung transplantation, corona virus disease 2019 (COVID-19)-associated cardiovascular collapse. Also, we look forward to making more suggestions for clinicians' judgment and choice for VA-ECMO.

[Analysis of the characteristics of MRI T2 value changes of the muscles around the knee joint before and after the race in amateur marathon runners based on T2 mapping].

Objective: To evaluate the characteristics of MRI T2 value changes of muscles around the knee joint in amateur marathon athletes based on T2 mapping. Methods: A total of 12 amateur marathon runners (5 males and 7 females) were recruited as the marathon group, aged from 21 to 37(27.5±5.4) years. MRI examination of bilateral knee joint was performed one week before the race, within 12 hours after the race and two months after the race, respectively. Fifteen healthy volunteers (5 males and 10 females) were recruited as the control group, aged from 24 to 27(24.9±1.0) years, and underwent MRI examination of both knee joints. The T2 mapping imaging sequence was used to measure the T2 values of the sartorius, vastus medialis, biceps femoris, semimembranosus, medial head of gastrocnemius and lateral gastrocnemius head on the post-processing platform, and analyzed the marathon group before and after the race. The differences in the T2 value of each muscle of the marathon group before and after the race within 12 hours, before and 2 months after the race, and between the control group and the marathon group before the marathon were analyzed. Results: All subjects had not knee joint pain during the examination. Routine MRI examination showed that there was no obvious abnormality in the shape and signal of the muscles around the knee joint. The T2 value of the semimembranosus [(34.3±2.8) ms vs (35.5±2.5) ms, P=0.008], medial head of gastrocnemius [(34.1±3.4) ms vs (37.7±3.1) ms,P<0.001] and lateral head of gastrocnemius [(35.2±2.9) ms vs (37.2±3.9) ms,P=0.011] increased after the competition compared with that of pre-competition in the marathon group, while the T2 value of the remaining muscles showed no significant difference compared with that of pre-competition(P>0.05). At the follow-up of 2 months, the T2 value of semimembranosus remains higher than before the marathon [(34.3±2.8) ms vs (35.4±2.5) ms,P=0.043], and the T2 value of the medial head of the gastrocnemius and lateral head of gastrocnemius showed no statistically difference compared with pre-competition (P>0.05). Compared with the control group, the T2 value of the lateral head of the gastrocnemius in the marathon group was decreased [(35.3±3.0) ms vs (38.5±4.1) ms,P=0.007]. There was no significant difference in the T2 value of the remaining muscles in the marathon group (P>0.05). Conclusions: After the marathon, the changes in the T2 value of the muscles around the knee joint is reversible. T2 mapping imaging sequence can indirectly reflect the changes of skeletal muscle microstructure to a certain extent.

[Progress in treatment for malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a kind of invasive malignant tumor originated from pleural tissue. The incidence of MPM is not high in the population, but the prognosis is very poor. The median survival time is only about 12 months. Pemetrexed combined with platinum is the first-line chemotherapy regimen recommended by the current guidelines. The use of bevacizumab will further prolong the survival of chemotherapy. Once resistance happened, no anti-tumor treatment has been confirmed to achieve survival benefits. Therefore, there is no recommended standard second-line MPM regimen in international and domestic guidelines, including National Comprehensive Cancer Network (NCCN) guidelines. Vinorelbine, gemcitabine and other monotherapy regimens are commonly used in clinical practice, but the median progression free survival (PFS) is only about 3 months. Immune checkpoint inhibitors (ICIS) have been proved to have a significant inhibitory effect on tumor growth in a variety of malignant tumors, and their efficacy is related to the expression of programmed death-ligand 1(PD-L1). In unresectable MPM, programmed death 1 (PD-1)/PD-L1 inhibitors have been used in a series of clinical studies in the first-line, second-line and above treatment. Some of the results have been cited and recommended by international guidelines, but the overall efficacy improvement is still limited. This review summarizes the latest clinical studies and researches in the field of MPM treatment and predicts the directions and prospect of improving the therapeutic effect in the future.

[A case of acute exudative polymorphous vitelliform maculopathy].

A 35-year-old male patient presented to the hospital with binocular blurred vision for 2 weeks. The visual acuity of both eyes was 0.8. Fundus examination showed multiple yellow-white punctate lesions in the posterior pole of both eyes. OCT showed cystoid edema and submacular edema, thickening of ellipsoid zone and enhancement of reflex in macular region. Fundus autofluorescence showed strong autofluorescence at the lesion site. Fundus fluorescein angiography showed no fluorescence leakage in the lesion area. The patient was diagnosed with acute exudative polymorphous vitelliform maculopathy based on medical history, ocular multimodal examination and general examination. The patient was not given special treatment, but one week later, the lesion was fused and expanded, and the macular edema was worse than before.

[Mechanical analysis of the impact of the morphology of the iris and ciliary body on the central vault after posterior chamber phakic intraocular lens implantation].

Objective: To investigate the impact of the iris and ciliary body morphology on the central vault after phakic posterior chamber intraocular lens (pIOL) implantation. Methods: This research was based on the retrospective analysis of 123 patients (123 eyes) who underwent pIOL implantation in the Department of Ophthalmology, Affiliated Hospital of Qingdao University between June 2018 and June 2020. The anterior segment structure was observed with an ultrasound biomicroscope before surgery, and all morphological parameters of the iris and ciliary body were measured manually using the ImageJ software, including iris span (IS), iris convexity (IC), iris-ciliary body contact distance (ICCD) and iris-lens contact distance (ILCD). The ICCD was divided into Q1, Q2 and Q3 groups according to the equidistant distance of 0.36 mm. The lens thickness was measured with the IOLMaster. The horizontal corneal diameter and anterior chamber depth were measured using the Pentacam. The central vaults were measured by optical coherence tomography at 1 week, 3 months and 1 year after surgery. The relationships between vault values and preoperative parameters of the anterior segment were evaluated using the Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression. The repeated measures ANOVA was applied to identify changes of vault values over time. Results: The mean values of the vaults at 1 week, 3 months and 1 year after surgery were (723±265) µm, (642±255) µm and (613±280) µm, respectively. The difference among them was statistically significant (F=50.143, P<0.001). The vaults continued to decline within 1 year after pIOL implantation, and the total decline was (122±86) µm. The vaults declined by (69±98) µm from postoperative 1 week to 3 months and by (52±54) µm from postoperative 3 months to 1 year. The regression formula showed that the pIOL size and ILCD were positively related with the vault, while the LT, IS and IC were negatively related with the vault at 1 week postoperatively (adjusted R²=0.404, P<0.001). The pIOL size and ILCD were positively related with the vault, while the IS and IC were negatively related with the vault at 3 months postoperatively (adjusted R²=0.342, P<0.001). The pIOL size was positively related with the vault, while the IS and IC were negatively related with the vault at 1 year postoperatively (adjusted R²=0.661, P<0.001). The vault values were higher in group Q3 compared to group Q1 at every timepoint, and the vault value was higher in group Q2 compared to Q1 at 1 year postoperatively. Conclusions: In the early postoperative period, eyes with a larger pIOL, shorter iris span, longer contact distance between the iris and ciliary body, and longer contact distance between the iris and lens were associated with a higher rate of excessive vaults. Meanwhile, eyes with a thicker lens and larger iris reverse convexity were more likely to obtain insufficient vaults. Within one year after surgery, the pIOL size, IS, IC and ICCD continued to impact on the vault. The ICCD, ILCD and IC can reflect the posterior chamber volume and change the haptic location and force, thus affecting the vault.

[Lipoprotein apheresis in patients with familial hypercholesterolemia: a single center research].

Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.

[One case of extensive high-pressure injection injury of hand caused by polyurethane material].

This article reports a patient with extensive high-pressure injection injury of the hand caused by mistaken injection of polyurethane material into the index finger, who was diagnosed and treated in the Department of Orthopedics of Huzhou Central Hospital in 2019. Both the digital artery and digital nerve were involved, and the polyurethane involved the right palm along the flexor tendon sheath of the index finger and wrist. Due to the lack of X-ray development, the scope of the first debridement was small, and the blood supply to the fingertip was poor. Finally, the patient's right index finger was amputated due to infection and necrosis. MR or B-ultrasound should be perfected before operation to clarify the extent of polyurethane involvement. The initial thorough debridement or multiple debridements are necessary to improve the prognosis. If the blood supply of the fingers is poor, the blood supply can be reconstructed by skin flap transplantation.

[Neoadjuvant chemotherapy in breast cancer of consensuses and controversial perspectives].

Neoadjuvant chemotherapy (NACT) is a vital part of the systemic treatment to breast cancer. With the formation of consensuses on NACT, controversial perspectives on NACT have been widely discussed, especially in the fields of indication and therapeutic strategy. To define the indication of NACT, blind obedience to the results of clinical trials is not recommended. Instead, indications of NACT should be strictly controlled based on the targets of the clinical practice. Oriented by the early effectiveness of NACT, various chemotherapy or local therapeutics for different molecular subtypes of breast cancer should be conducted to the patients with unsatisfied effect. What's more, the evolvement of precision medicine accelerates the research of drugs and helps to form an individualized NACT plan. After clarifying the controversial opinions towards NACT in breast cancer, controlling the indication and optimizing the therapeutic strategy will improve the survival of breast cancer patients.

[The clinical significance of non-traditional lipid parameters should be concerned].

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of human deaths all over the world. Dyslipidemia is the central mechanism of the prevalence and development of ASCVD, which has been regarded as a remediable risk factor for cardiovascular disease. It's well known that the traditional lipid parameter, low-density lipoprotein cholesterol (LDL-C), is the primary target for lipid interfering in ASCVD. However, both randomized controlled trials and real-world studies have suggested that residual risk persists in spite of the well-controlled LDL-C levels according to current guidelines. Hence, in recent years, a series of studies have indicated that many novel lipid indicators are closely correlated with the residual risk of ASCVD. This article aimed to summarize the research status of these non-traditional lipid parameters in cardiovascular field.

[Effect of bone marrow stimulation on arthroscopic repair of anterior talofibular ligament].

Objective: To investigate the effect of simultaneous bone marrow stimulation in the treatment of osteochondral lesions of the talus (OLTs) on arthroscopic repair of anterior talofibular ligament. Methods: The clinical data of 33 patients with ankle instability treated by operation in Sun Yat-Sen Memorial Hospital from January 2018 to December 2019 were retrospectively analyzed. There were 20 males and 13 females with a mean age of (31±9) years. According to the type of surgery, the patients were divided into two groups: ligament repair group (arthroscopic anterior talofibular ligament repair) and bone marrow stimulation group (arthroscopic anterior talofibular ligament repair+talus microfracture). Visual analogue scale (VAS), American Orthopedic Foot And Ankle Society (AOFAS) score, time to return to work and time to return to sport were compared between the two groups. Results: In the ligament repair group, the preoperative VAS score and the AOFAS score was 5.0±1.9 and 72.4±9.0, respectively, and it was 1.1±1.6 and 95.5±5.2 at the last follow-up, respectively. In the bone marrow stimulation group, the preoperative VAS score and the AOFAS score was 5.8±1.9 and 64.8±12.6, respectively, and it was 1.8±1.5 and 93.1±5.6 at the last follow-up, respectively. The scores of VAS and AOFAS were significantly improved in both groups after the operation, but there was no significant difference between the two groups (both P>0.05). There was no significant difference in time to return to work and return to sport between the two groups (both P>0.05). Conclusion: When repairing the anterior talofibular ligament under arthroscopy, simultaneous bone marrow in the treatment of osteochondral lesions of the talus does not affect the postoperative functional recovery and the time to return to work/sport, and satisfactory clinical results also can be obtained.