Comparison of the Similarities and Differences between ZHU Danxi's and ZHANG Jingyue's Understanding of Yin Deficiency and the Treatment Method of Nourishing Yin / 浙江中医药大学学报

[Objective]To sort out and summarize the theory of nourishing Yin of ZHU Danxi and ZHANG Jingyue,and discuss the similarities and differences of two doctors'understanding of Yin deficiency and the treatment method of nourishing Yin.[Methods]Through the research method of documentics,this paper carefully studies the contents related to"Yin deficiency"in the major works of ZHU Danxi and ZHANG Jingyue,as well as relevant literature reports and analyzes the similarities and differences of the theory of nourishing Yin,classification of Yin deficiency and the treatment method of nourishing Yin between them.[Results]ZHU Danxi's treatment of Yin deficiency syndrome was based on the theory of"an excess of Yang with deficiency of Yin""ministerial fire(Xianghuo)".He took the hyperactivity of ministerial fire as the main pathogenesis of Yin deficiency syndrome.In the treatment method,he paid attention to reducing fire,and made good use of the bitter and cold products such as Anemarrhenae Rhizoma(Zhimu)and Cortex Phellodendri(Huangbai),and paid equal attention to nourishing Yin and reducing fire.ZHANG Jingyue,on the basis of the theory that"Yin and Yang are one"and"true Yin was the foundation of Yang Qi",believed that the deficiency of true Yin can lead to Yin deficiency and Yang deficiency,and proposed that Yin deficiency had two aspects:water deficiency in Yin and fire deficiency in Yin.In the treatment method,nourishing true Yin by the sweet and warm medicines such as Radix Rehmanniae Preparata(Shudihuang)was emphasized,and Yin Yang mutual aid was advocated.[Conclusion]Whether it is the thought of nourishing Yin or the specific treatment and prescription,ZHANG Jingyue inherited and made a breakthrough on ZHU Danxi.He further improved the theory of nourishing Yin and the theory of warm-recuperation in traditional Chinese medicine,and created a series of prescriptions based on nourishing true Yin.It is of great significance to study the similarities and differences of their thought,theory,clinical symptoms and treatment for sorting out the development context of the treatment method of nourishing Yin.

Analysis on the Dosage， Dose and Administration Method of Decoctions in Ming and Qing Dynasties Based on Catalogue of Ancient Classic Famous Formulas （First Batch） / 中医杂志

The dosage， dose and administration method of decoctions are important factors affecting the efficacy of prescriptions. By analyzing 35 decoction formulas from the Ming and Qing dynasties within the Catalogue of Ancient Classic Famous Formulas （First Batch）， it was found that the average dosage was equivalent to about 65 g， of which 71.4% （25/35） of the prescriptions had a dosage ≤60 g. And among them， the dosage of decoctions in the Ming dynasty was significantly smaller than that in the Qing dynasty. Considering the characteristics of formulas in Song dynasty， it is believed that decoctions in Ming and Qing dynasties were influenced by the popular use of decoctions during the Song， Jin， and Yuan dynasties. Some decoctions recorded a dosage of one dose instead of one day， which was more evident in the Ming dynasty. However， by the Qing dynasty， the usage of prescriptions with a dosage of one day gradually became more common. Therefore， in the practical research and application of classic famous formulas from the Ming and Qing dynasties， it is advised to pay attention to the difference between the dosage， one dose and the daily dosage. It is necessary to determine whether to double the dosage of the original formula based on the actual use， in order to ensure the clinical efficacy.

Textual Research on Principle of Dose Conversion in Ancient Famous Classical Formulas / 中国实验方剂学杂志

Due to the difference between the system of weights and measures， and the dosage of clinical prescriptions of traditional Chinese medicine in various historical periods， the dosage and conversion standard of prescriptions in past dynasties are different. Therefore， when discounting the dosage of famous classical formulas， the principles of inheriting the essence， making the past serve the present， linking the past and the present， and forming a consensus should be followed， firstly， the dosage of the prescription was converted according to the weights and measures system of the past dynasties. If the converted dosage significantly exceeds the provisions of the 2020 edition of Chinese Pharmacopoeia， then on the premise of ensuring that the proportion of the original prescription drug dosage remains unchanged， the conversion shall be based on expert consensus and drug safety evaluation. For drugs measured in non-standard units， a conversion range is provided based on comprehensive literature analysis and physical measurements. For the conversion of service volume， the original text was used as the basis for the conversion with reference to the measurement standards of different eras. If the original dosage is not clear， the converted dosage will be determined based on the historical evolution of the formula， referring to relevant ancient books， and combining modern applications. Eventually， the converting standard for famous classical formulas was determined as follows：during the Han and Tang dynasties， one Liang（两） was equivalent to 13.8 g and one Sheng（升） was equivalent to 200 mL， in the Tang dynasty， one Fen（分） was equivalent to 3.45 g， during the Song， Jin and Yuan dynasties， one Qian（钱） was equivalent to 4.13 g and one Zhan（盏） was equivalent to 300 mL， during the Ming and Qing dynasties， one Qian（钱） was equivalent to 3.73 g， and one Bei（杯） and one Zhong（盅） were equivalent to 200 mL. For drugs recorded in non-standard units of measurement， it is necessary to conduct actual measurements to determine their conversion standards based on comprehensive analysis to determine their origin. If necessary， different records of the dosage of drugs with the same or similar efficacy and indications in medical books of similar ages can be used to assist in determining the conversion standards. The analysis of the principle of dosage conversion for Chinese medicine is helpful for the clinical application and development of famous classical formulas.

Study on the Utilization Status and Influencing Factors of Health Management Services for Floating Elderly Population with Chronic Diseases:a Comparative Analysis based on the Differences between Urban and Rural Areas / 中国卫生统计

Objective Our study systematically analyzed the utilization status and influencing factors of health management services for floating elderly patients with chronic diseases in China,and compares the differences between urban and rural areas,in order to provide countermeasures and suggestions for realizing the equalization of basic public health services and improving the quality of life and health level of floating elderly population.Methods We used the dynamic monitoring survey data of China's floating population in 2017,floating elderly aged 60 and above with chronic diseases diagnosed by doctors were selected as the research objects.Under the guidance of social ecological theory,the binary logistic regression model was used to analyze the influencing factors of the utilization of health management services by floating elderly patients with chronic diseases in the whole,rural and urban areas.Results Among the 2158 floating elderly patients with chronic diseases,the utilization rate of health management services was 46.6%,47.2%in rural areas and 45.9%in urban areas.The results of binary logistic regression showed that gender,age,self-rated health status,two-week visiting rate,family monthly income,whether they had heard of national basic public health projects,flow range,flow time and inflow region had an impact on the utilization of health management services by floating elderly patients with chronic diseases(P<0.05).Conclusion The utilization rate of health management services for floating elderly patients with chronic diseases in China is low.Service utilization is affected by multidimensional factors such as personal characteristics,individual behavior,interpersonal level,social environment and mobility characteristics,and there are some differences between urban and rural areas.

Analysis of clinical, imaging and gene mutations in 2 pedigrees with hereditary spastic paraplegia type 7 / 中华神经科杂志

Objective:To analyze the clinical, imaging and genetic characteristics of 2 pedigrees with hereditary spastic paraplegia type 7 (SPG7).Methods:The clinical data of the probands and related members of 2 families hospitalized in the Department of Neurology of Henan Provincial People′s Hospital from December 2018 to December 2021 were collected. The probands and all family members were subjected to cranial MRI imaging and genetic testing, and the clinical characteristics and genetic variation of SPG7 families were compared with those reported in the literature.Results:Four patients from the 2 families were observed with adult-onset age in this group. The main manifestations were wide-base ataxic gait in 4 cases, and spastic gait in 1 case during follow-up. Pyramidal tract involvement mainly in the lower limbs were found in all cases, and dysarthria in 3 cases. MRI of 3 patients showed varying degrees of cerebellar atrophy. Genetic testing revealed compound heterozygous or homozygous variants of the SPG7 gene in the 4 patients, of which c.2062C>T and c.2176C>T were novel mutations. At present, only 5 SPG7 families have been reported in China. Among the 12 patients in all groups, 12 cases of pyramidal tract involvement, 10 cases of cerebellar ataxia, 7 cases of dysarticulation, 3 cases of cognitive impairment, 11 cases of complex hereditary spastic paraplegia, 1 case of simple hereditary spastic paraplegia, and 9 cases of cerebellar atrophy were reported. Six novel mutations have been reported in 5 families. Conclusions:SPG7 family is rarely reported in China, mainly manifested as pyramidal tract involvement combined with cerebellar ataxia, accompanied by cerebellar atrophy. SPG7 mutation is confirmed by genetic detection, and there are many novel mutations in SPG7 family in China.

Dilemmas and strategies for collaborative governance of medical preventive integration based on SFIC model / 中华医院管理杂志

Promoting medical preventive integration and improving its collaborative mechanism is an inevitable requirement for achieving the transformation of China′s medical and health care system from " disease centered" to " people′s health centered" and providing comprehensive and comprehensive health services for the people.This study established a research framework based on the SFIC model on the basis of clarifying the collaborative subjects of medical preventive integration, sorted out the dilemma of medical preventive integration collaborative governance in China from five aspects, including external environment, starting conditions, facilitative leadership, institutional design and collaborative process.In order to break the dilemma of medical preventive integration and promote collaborative governance among multiple subjects, the authors proposed such optimization strategies, including further improving relevant laws, regulations, and policy systems, filling resource gaps, attracting multiple entities to participate, providing reference for promoting China′s medical preventive integration work.

Basic research on toxin of Solenopsis invicta / 药学实践与服务

Solenopsis invicta is a kind of invasive pest that causes serious damage to local agriculture, environment, and human health. They attack mainly with venom within stingers. Those who are allergic to the venom would suffer a systemic anaphylaxis, even fatal shock, after being stinged by these ants. Many studies reveal that their venom is mainly composed by water, insoluble alkaloids and trace proteins, within which alkaloids are the main cause of burning sensation and blisters, while allergic reactions are caused by proteins or peptides. The research progress of toxic substances in the venom of Solenopsis invicta as well as the roles and functions of each component were reviewed in this paper.

Analysis of the clinical, pathological and genetic features of patients with myopathy-type very long chain acyl-coenzyme A dehydrogenase deficiency / 中华神经科杂志

Objective:To investigate the clinical, pathological and genetic characteristics of myopathy-type very long chain acyl-coenzyme A dehydrogenase deficiency (VLCADD).Methods:The detailed clinical data, muscle biopsy pathology and molecular results of 4 patients with genetically confirmed myopathy-type VLCADD admitted to Henan Provincial People′s Hospital and Xuanwu Hospital, Capital Medical University from June 2014 to November 2019 were retrospectively analyzed.Results:All of the 4 patients were late-onset myopathy-type VLCADD. The onset age ranged from 13 to 16 years, with a mean age of 14.5 years. The age at diagnosis ranged from 21 to 54 years, with a mean age of 42.5 years. The main clinical manifestation was repeated rhabdomyolysis, including myalgia, weakness and dark urine. Obvious somnolence was observerd in 1 patient. Muscle biopsy pathology revealed mild lipid accumulation, without vacuoles. Six ACADVL variations were detected in the 4 patients, including c.1283G>A (p.R428H), c.1532G>A (p.R511Q), c.833_835delAGA (p.K278del), c.1843C>T (p.R615 *), c.1748C>T (p.S583L) and c.1391C>T (p.T464I),among which c.1391C>T (p.T464I) was a novel variation, predicted to be likely pathogenic. Other 5 variations were reported pathogenic variations. Conclusions:Myopathy-type VLCADD is characterized by paroxysmal rhabdomyolysis and can be associated with somnolence. There is no specificity in muscle pathology. There are ACADVL variations, among which c.1391C>T is a novel variation.

Muscle MRI features of the lower extremities in patients with limb girdle muscular dystrophy type R1 / 中华神经医学杂志

Objective:To investigate the muscle MRI features of the lower extremities and correlations between MRI fatty degeneration total scores and other clinical features in limb girdle muscular dystrophy type R1 (LGMDR1) patients.Methods:Clinical data of 8 patients with LGMDR1 diagnosed by genetic examination in Department of Neurology, He'nan Provincial People's Hospital&People's Hospital of Zhengzhou University from May 2016 to November 2021 were retrospectively analyzed. Disease severity was evaluated by Gardner-Medwin and Walton (GM-W) scale. Pathological staining results of the lower limb muscles were observed; the fatty infiltration and edema of the muscles were observed by MRI T1WI and short-tau inversion recovery (STIR) sequences. Lower limb muscles were scored using Mercuri's scale. Spearman rank correlation was used to analyze the correlations of MRI fatty degeneration total scores of the lower extremities with age, age of onset, disease duration, GM-W scale scores and creatinine kinase (CK) level.Results:Of the 8 patients with LGMDR1, 7 had decreased muscle strength in the proximal lower extremity, including 4 with decreased muscle strength in the distal lower extremity at the same time. Muscular dystrophy-like pathological changes of skeletal muscles were noted. All 8 LGMDR1 patients showed different degrees of fatty infiltration in the lower extremities: at the thigh level, the adductor magnus, biceps femoris long head, semimembranes, semitendinosus and adductor longus were the most severely fatty degeneration muscles (mean scores>4), with relatively sparing of the sartorius and rectus femoris; regarding the calves, gastrocnemius medial head was the mostly involved, followed by soleus, with relative sparing of the tibialis posterior and anterior compartment. Edema-like changes (mild) were observed in 7 patients; the muscles that most frequently and relatively severely displayed edema-like changes were the gastrocnemius lateral head and quadriceps. The fatty degeneration total scores of the lower extremities were positively correlated with GM-W scale scores ( r=0.872, P=0.005) and negatively correlated with CK level ( r=-0.929, P=0.001), but not significantly correlated with age, age of onset or disease duration ( r=0.635, P=0.091; r=0.571, P=0.139; r=0.551, P=0.157). Conclusion:The lower limb muscles with severe fatty infiltration are less prone to show edema-like changes; fatty degeneration can be used to evaluate LGMDR1 progress; involvement pattern of muscle MRI of the lower extremities is helpful in diagnosing and differentially diagnosing LGMDR1.

Latent class growth model-based study of demoralization syndrome among maintenance hemodialysis patients in young and middle-aged adults / 中国实用护理杂志

Objective:To investigate distinct trahectories of demoralization of maintenance hemodialysis patients in young and middle-aged adults, and analyze the factors that affect the trajectory category, so as to provides reference for formulating individualized intervention strategies.Methods:This study was a cross-sectional survey. From April 2020 to April 2021, young and middle-aged maintenance hemodialysis patients fromShangyu People′s Hospital were collected by convenience sampling method and conducted 4-time follow-up investigation. The survey tools included general information questionnaire, Demoralization Scale Mandarin Version (DS-MV) and Experiences in Close Relationship Scale-Short Form (ECR-S). Latent class growth model was used to identify trajectory patterns of demoralization, Logistic regression was used to identify predictors of demoralization trajectories.Results:Totally, 105 patients were enrolled in the present study. Three distinct trajectories were identified and named as "table high level group" 24 cases, "slow reduction group" 39 cases and "continuous reduction group" 42 cases. Univariate analysis showed that age, occupational status, average income per person in family, number of comorbidities, attachment anxiety scores were related to the category of demoralization trajectories ( F = 15.92, χ2 values were 9.16-15.95, all P<0.05). Multivariate Logistic regression analysis showed that age, occupational status, average income per person in family, number of comorbidities, and attachment anxiety scores were important predictors of patterns of demoralization trajectories in young and middle-aged maintenance hemodialysis patients. Conclusions:This study identified three distinct demoralization trajectories in young and middle-aged maintenance hemodialysis patients, clinical nursing should formulate individualized intervention strategies according to the types of patients′ delirium trajectories.

Impact of sinonasal anatomic changes after endoscopic anterior skull base surgery on nasal airflow and air conditioning: a computational fluid dynamics study / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the impact of the sinonasal anatomic changes after endonasal endoscopic anterior skull base surgery on the nasal airflow and heating and humidification by computational fluid dynamics (CFD), and to explore the correlation between the postoperative CFD parameters and the subjective symptoms of the patients. Methods: The clinical data in the Rhinology Department of the First Affiliated Hospital of Zhengzhou University from 2016 to 2021 were retrospectively analyzed. The patients received the endoscopic resection of the anterior skull base tumor were selected as the case group, and the adults whose CT scans had no sinonasal abnormalities were chosen as the control group. The CFD simulation was performed on the sinonasal models after reconstructed from the patients' sinus CT images during the post-surgical follow-up. All the patients were asked to complete the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) to assess the subjective symptoms. The comparison between two independent groups and the correlation analysis were carried out by using the Mann-Whitney U test and the Spearman correlation test in the SPSS 26.0 software. Results: Nineteen patients (including 8 males and 11 females, from 22 to 67 years old) in the case group and 2 patients (a male of 38 years old and a female of 45 years old) in the control group were enrolled in this study. After the anterior skull base surgery, the high-speed airflow moved to the upper part of the nasal cavity, and the lowest temperature shifted upwards on the choana. Comparing with the control group, the ratio of nasal mucosal surface area to nasal ventilation volume in the case group decreased [0.41 (0.40, 0.41) mm-1 vs 0.32 (0.30, 0.38) mm-1; Z=-2.04, P=0.041], the air flow in the upper and middle part of the nasal cavity increased [61.14 (59.78, 62.51)% vs 78.07 (76.22, 94.43)%; Z=-2.28, P=0.023], the nasal resistance decreased [0.024 (0.022, 0.026) Pa·s/ml vs 0.016 (0.009, 0.018) Pa·s/ml; Z=-2.29, P=0.022], the lowest temperature in the middle of the nasal cavity decreased [28.29 (27.23, 29.35)℃ vs 25.06 (24.07, 25.50)℃; Z=-2.28, P=0.023], the nasal heating efficiency decreased [98.74 (97.95, 99.52)% vs 82.16 (80.24, 86.91)%; Z=-2.28, P=0.023], the lowest relative humidity decreased [(79.62 (76.55, 82.69)% vs 73.28 (71.27, 75.05)%; Z=-2.28, P=0.023], and the nasal humidification efficiency decreased [99.50 (97.69, 101.30)% vs 86.09 (79.33, 87.16)%; Z=-2.28, P=0.023]. The ENS6Q total scores of all patients in the case group were less than 11 points. There was a moderate negative correlation between the proportion of the inferior airflow in the post-surgical nasal cavity negatively and the ENS6Q total scores (rs=-0.50, P=0.029). Conclusions: The sinonasal anatomic changes after the endoscopic anterior skull base surgery alter the nasal airflow patterns, reducing the efficiency of nasal heating and humidification. However, the post-surgical occurrence tendency of the empty nose syndrome is weak.

Surgical strategies of atlantoaxial dislocation in mucopolysaccharidosis IVa / 中华骨科杂志

Objective:To discuss the surgical strategies of atlantoaxial dislocation in children with mucopolysaccharidosis IVA.Methods:8 cases of atlantoaxial dislocation in children with mucopolysaccharidosis IVA treated with posterior atlantoaxial reduction, decompression, bone graft and internal fixation from April, 2019 to October, 2020 were retrospectively analyzed, including 6 males and 2 females, aged 6.2±3.1 years (range, 2-10 years). All the 8 children had lower limb weakness and walking instability, and some of them could not even stand and walk, and all of them had odontoid hypoplasia, atlantoaxial dislocation and systemic skeletal dysplasia. Measures, including American Spinal injury Association (ASIA) grade, modified atlanto-dental interval (mADI) and reduction rate, screw placement type and fusion of bone graft, were recorded and analyzed.Results:The follow-up time was 17.8±7.4 months (range, 8-27 months). The total operation time was 144.0±43.1 mins (range, 90-220 min) and the blood loss during the surgery was 89.1±55.1 ml (range, 15-180 ml). The ASIA grade were 3 cases of "C" level, 4 cases of "D" level and 1 case of "E" level before the operation, and 1 case of "C" level, 1 case of "D" level and 6 cases of "E" level at the latest follow-up. The mADI reduced from 7.38±2.62 mm pre-surgery to 2.50±1.60 mm ( t=5.71, P=0.001). The reduction rate of the latest follow-up mADI was 65.0%±26.3%. 31 pedicle screws were inserted, including 26 Type I screws (83.9%), 4 Type II screws (12.9%) and 1 Type III screw (3.2%), and no injury of spinal cord or blood vessels were observed associated with the Type III screw. One unilateral axial lamina screw was used in 1 case. 5 patients showed fusion (autogenous bone) 6 months after the surgery, 2 patients got fusion (allogeneic bone) 1 year after the surgery, and other patients showed bone graft resorption (allogeneic bone) at the latest follow-up. One patient developed type II respiratory failure on the night of operation and recovered after rescue. Other patients had no complications such as vascular and nerve injury, screw loosening and so on. Conclusion:The majority of children with type IVa mucopolysaccharidosis are accompanied by absence of odontoid process. If such children are complicated with atlantoaxial dislocation and cervical spinal canal stenosis resulting in cervical spinal cord injury, timely surgical intervention should be carried out. Posterior atlantoaxial fusion is a safe and effective surgical method. As children have the characteristics of multi-system involvement, multi-disciplinary cooperation may be needed to ensure perioperative safety.

Clinical and genetic features of 12 families with Pompe disease / 中华神经医学杂志

Objective:To investigate the clinical and genetic features of Pompe disease, and analyze the effect of enzyme replacement therapy on it.Methods:A retrospective study was performed. The clinical data and genetic results of 14 patients with Pompe disease from 12 families, admitted to our hospital from January 2017 to June 2021, were collected. Some patients were followed up after therapies.Results:Twelve of the 14 patients were late onset, with onset age ranged from 1.5 to 37.0 years (mean 15.2 years), and the other 2 patients were infantile onset. The predominant manifestations included proximal lower limb weakness, accompanied by easy fatigue and myalgia; 8 patients presented with dyspnea, of which one had dyspnea as initial presentation. Serum creatine kinase ranged from 172 to 1397 IU/L (mean 878 IU/L). Electromyography revealed myogenic pattern in 6 patients and myotonic discharge in 4 patients. Forced vital capacity decreased in 10 patients, and scoliosis was detected in 5 patients; 13 patients had decreased acid-alpha-glucosidase (GAA) activity; muscle pathology indicated vacuolar myopathy in 8 patients. Genetic test revealed 17 variants in GAA gene, among which c.2331G>C, c.1622C>T, c.1585T>C, and c.1837T>C were 4 novel likely pathogenic variants. The c.2238G>C and c.2662G>T were found in 5 and 3 families, respectively. Muscle strength and lung function got improvement in 1 patient who received enzyme replacement therapy and had regular follow-up, while muscle strength and lung function were worsened in those who did not receive enzyme replacement therapy. Conclusions:Pompe disease is characterized by skeletal muscle weakness and pulmonary dysfunction, and may be associated with spinal deformity; creatine kinase is mildly to moderately elevated, and myotonic discharge can be detected. GAA c.2238G>C and c.2662G>T are hotspot mutations in China; the 4 novel variants enrich the GAA mutational spectrum. Enzyme replacement therapy may improve motor and pulmonary function.

Analysis on the incidence and risk factors of pneumonia in patients with lung cancer receiving thoracic radiotherapy and immunotherapy / 国际肿瘤学杂志

Objective:To analyze the incidence, risk factors and occurrence time of radiation pneumonia (RP) and immune checkpoint inhibitor-related pneumonia (CIP) in patients with lung cancer and lung metastatic cancer who received both thoracic radiotherapy and immunotherapy.Methods:The clinicopathological data of 137 patients with lung cancer and lung metastatic cancer receiving thoracic radiotherapy and at least one cycle of immunotherapy from January 2019 to January 2022 in Renmin Hospital of Wuhan University were retrospectively analyzed. The occurrence of RP and CIP was determined according to the clinical symptoms and thin-slice chest CT. The risk factors of symptomatic RP were evaluated by univariate and multivariate analyses of clinical data and treatment plan. The relationship between the occurrence time of symptomatic RP and the sequence of thoracic radiotherapy and immunotherapy was compared.Results:In the 137 patients with lung cancer and lung metastatic cancer who received both thoracic radiotherapy and immunotherapy, symptomatic RP was observed in 42 patients (30.7%) , including grade 2 RP in 33 patients (24.1%) , grade 3 RP in 6 patients (4.4%) , grade 4 RP in 1 patient (0.7%) , and grade 5 RP in 2 patients (1.5%) . The incidence of symptomatic RP was 40.0% (28/70) in patients who received thoracic radiation concurrent with immunotherapy and 20.9% (14/67) in non-synchronous patients, and the incidence of severe RP was 10.0% (7/70) and 3.0% (2/67) respectively. CIP was observed in 11 (8.0%) of 137 patients, including grade 2 CIP in 4 patients (2.9%) , grade 3 CIP in 6 patients (4.4%) , grade 5 CIP in 1 patient (0.7%) . There were 54.5% (6/11) of CIP patients with prior or concurrent symptomatic RP. Univariate analysis showed that smoking history ( χ2=9.85, P=0.002) , chronic obstructive pulmonary disease (COPD) history ( χ2=31.34, P<0.001) , thoracic radiotherapy concurrent with immunotherapy ( χ2=5.88, P=0.015) , total radiotherapy dose ( χ2=8.57, P=0.003) were associated with symptomatic RP. Multivariate logistic regression analysis showed that COPD history ( OR=9.96, 95% CI: 3.40-29.14, P<0.001) , thoracic radiotherapy concurrent with immunotherapy ( OR=2.84, 95% CI: 1.15-7.00, P=0.024) , and total radiotherapy dose ≥60 Gy ( OR=4.76, 95% CI: 1.68-13.50, P=0.003) were independent risk factors for symptomatic RP. RP occurred earlier in patients who received immunotherapy before thoracic radiotherapy [68.5 d (47.0 d, 101.8 d) ] than in patients who received immunotherapy after thoracic radiotherapy [117.5 d (79.0 d, 166.3 d) ], with a statistically significant difference ( Z=2.54, P=0.010) . Conclusion:The incidence of symptomatic RP is high in patients who receive both thoracic radiotherapy and immunotherapy. The history of COPD, thoracic radiotherapy concurrent with immunotherapy, and the total radiotherapy dose ≥60 Gy are independent influencing factors of symptomatic RP in patients with thoracic radiotherapy combined with immunotherapy. Symptomatic RP occurs earlier in patients who receive immunotherapy before thoracic radiotherapy than in patients who receive immunotherapy after thoracic radiotherapy.

Application of TACE combined with molecular targeted therapy and immunotherapy in BCLC B/C hepatocellular carcinoma / 国际肿瘤学杂志

Transcatheter arterial chemoembolization (TACE) is the standard treatment for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) . However, TACE has some limitations, TACE combined with systemic therapy may be more beneficial to patients with BCLC stage B/C HCC. To explore the efficacy and safety of TACE combined with molecular targeted therapy, immunotherapy and molecular targeted therapy + immunotherapy in the treatment of B/C stage HCC of BCLC will provide new ideas for the clinical treatment of HCC.

Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.

A family study of autosomal recessive primary familial brain calcification caused by JAM2 gene mutation and literature review / 中华神经科杂志

Objective:To improve the clinician′s recognition of the clinical and molecular characteristics of primary familial brain calcification (PFBC).Methods:The detailed clinical information, imaging and molecular characteristics were analyzed in proband and family members of a genetically confirmed autosomal recessive PFBC family. The clinical and imaging features of junctional adhesion molecule 2 (JAM2) gene related PFBC were analyzed in combination with the literature review.Results:The proband was a 32-year-old man, with slurred speech and paroxysmal limb twitch as the first symptoms, accompanied by cognitive dysfunction, and rigidity in the limbs, with epilepsy in the past. Brain CT showed extensive, symmetrical, and bilateral calcification involving the cerebellum, basal ganglia, thalamus, subcortex and cortex. Other family members showed no related clinical symptoms. Brain CT of the parents of the proband showed no calcification. Gene testing of the proband revealed a homozygous c.685C>T(p.R229*) mutation in JAM2 gene, which has been reported as a pathogenic variation abroad, whereas has not been reported in China. The proband′s parents and children were found with heterozygous c.685C>T (p.R229*) mutation.Conclusions:Autosomal recessive inherited PFBC is a rare disease, and JAM2 mutation is a newly discovered pathogenic gene of PFBC in 2020. Patients with intracranial calcification should be alert of JAM2 gene mutation.

Effect of microRNA-221 targeting tissue inhibitor of metalloproteinase-2 to mediate Akt / mTOR signaling pathway on non-small cell lung cancer transplanted tumor mouse model / 解剖学报

Objective To explore the effects of miR-221 on tumor cell proliferation, migration and invasion in nonsmall cell lung cancer (NSCLC) xenograft model mice, and to preliminarily analyze its possible mechanism of regulating Akt/ mammalian target of rapamycin(mTOR) signaling pathway by targeting tissue inhibitor of metalloproteinase-2 (TIMP-2) on tumor cells in non-small cell lung cancer (NSCLC) through tumor-bearing nude mice. Methods The A549 cells were divided into control group, mimic group, TIMP-2 group and mimic+TIMP-2 group. The mimic group and TIMP-2 group were transfected with miR-221 mimic and TIMP-2 overexpression plasmids, respectively. The mimic + TIMP-2 group was simultaneously transfected with miR-221 mimic and TIMP-2 overexpression plasmids. The control group was transfected with the same amount of negative control plasmid. After transfection, the cells of each group were injected subcutaneously into the left forelimb to construct the corresponding 4 groups of NSCLC mouse models. The proliferation-related protein (Ki67) was detected by immunohistochemical staining to detected the effect of cell proliferation ability. Matrix metalloproteinase-2 (MMP-2) and N-cadherin proteins in each group were tested by Western blotting to assess and compare the abilities of migration and invasion. The levels of miR-221, TIMP-2 and Akt/ mTOR pathways in bone marrow and tumor tissues were detected by Real-time PCR and Western blotting. Results When co-transfected with wild type(WT)-TIMP-2 and miR-221 mimic, the relative luciferase activity in the cells reduced significantly (P<0. 05). Compared with the control group, the tumor mass, volume, Ki67, MMP-2 and N-cadherin protein expression levels, miR-221 and Akt/ mTOR pathway levels were increased significantly, while the levels of TIMP-2 mRNA and protein were significantly reduced in the mimic group (P<0. 05). Compared with the control group, the levels of TIMP-2 mRNA and protein in the TIMP-2 group increased significantly, while the other indicators decreased significantly (P<0. 05). Tumor tissue mass, volume, Ki67, MMP-2, Ncadherin, miR-221 and Akt/ mTOR pathway levels in mimic+TIMP-2 group were significantly lower than those in the mimic group and significantly higher than those in the TIMP-2 group, while TIMP-2 mRNA and protein levels were significantly higher than those in the mimic group and significantly lower than those in the TIMP-2 group (P<0. 05). Conclusion In the NSCLC transplanted tumor mouse model, miR-221 may mediate the Akt/ mTOR pathway by targeting the expression of TIMP-2 protein to promote cell proliferation, migration and invasion.

Clinical characteristics and risk factors for mortality in cancer patients with COVID-19 / 医学前沿

Patients with cancer are at increased risk of severe infections. From a cohort including 3060 patients with confirmed COVID-19, 109 (3.4%) cancer patients were included in this study. Among them, 23 (21.1%) patients died in the hospital. Cancer patients, especially those with hematological malignancies (41.6%), urinary carcinoma (35.7%), malignancies of the digestive system (33.3%), gynecological malignancies (20%), and lung cancer (14.3%), had a much higher mortality than patients without cancer. A total of 19 (17.4%) cancer patients were infected in the hospital. The clinical characteristics of deceased cancer patients were compared with those of recovered cancer patients. Multivariate Cox regression analysis indicated that a Nutritional Risk Screening (NRS2002) score ⩾ 3 (adjusted hazard ratio (HR) 11.00; 95% confidence interval (CI) 4.60-26.32; P < 0.001), high-risk type (adjusted HR 18.81; 95% CI 4.21-83.93; P < 0.001), tumor stage IV (adjusted HR 4.26; 95% CI 2.34-7.75; P < 0.001), and recent adjuvant therapy (< 1 month) (adjusted HR 3.16; 95% CI 1.75-5.70; P < 0.01) were independent risk factors for in-hospital death after adjusting for age, comorbidities, D-dimer, and lymphocyte count. In conclusion, cancer patients showed a higher risk of COVID-19 infection with a poorer prognosis than patients without cancer. Cancer patients with high-risk tumor, NRS2002 score ⩾ 3, advanced tumor stage, and recent adjuvant therapy (< 1 month) may have high risk of mortality.

6-Formylindolo3,2-bcarbazole alleviates lipopolysaccharide-induced acute lung injury via suppressing endoplasmic reticulum stress / 中华危重病急救医学

Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.