ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

[Efficacy and Prognostic Factors of Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia].

OBJECTIVE: To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors. METHODS: Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed. RESULTS: The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024). CONCLUSION: Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.

Rhodium-Catalyzed Selective Nucleophilic Cyclization/Cross-Coupling of Two ortho-Alkynylanilines Bearing Differential N-Substituents.

Herein, we reported an effective selective nucleophilic cyclization/cross-coupling cascade reaction of N-tosyl ortho-alkynylanilines and N-acyl ortho-alkynylanilines using Rh(COD)2BF4/tBuXantPhos as a catalyst. The present protocol features excellent chemo- and regioselectivity, high atom-economy, and a broad range of substrates. The mechanism studies indicated that the key to the success of this reaction is the powerful capacity of the rhodium catalyst to recognize the N-substituent group in the selective nucleophilic cyclization and selective alkyne insertion.

Age-Related Changes of Biomechanical Properties for Limb Bones in Male Rats / 医用生物力学

Objective To investigate the age-related changes of biomechanical properties for humerus, femur and tibia in male rats and their application values in age estimation. Methods According to different weeks of age, 90 healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52, 78 and 104-week groups with 10 rats in eachgroup. After the rats were executed by excessive anesthesia, humerus, femur, and tibia were separated and the attached soft tissues were removed. The length of the above-mentioned bones and the diameter of the middle section (compression site) were measured with vernier caliper, and the three-point bending test was conducted with electronic universal material testing machine to detect the ultimate load and displacement under ultimate load. Results There were significant differences in the ultimate load of humerus, femur and tibia among male rats in different age groups (P<0. 05). With the increase of week age, the ultimate loads of the humerus, femur and tibia increased first and then decreased, and reached the peak value in 52-week age group, showing a strong positive correlation with week age before 52 weeks ( r = 0. 884,0. 933,0. 929, P<0. 05). There was no significant difference in humerus and tibia. The displacement of femur under ultimate load was weakly positively correlated with week age (R= 0. 406,P<0. 05). The age prediction accuracy for automatic linear modeling of ultimate load for humerus, femur, tibia and three above-mentioned bones in rats before 52-week age was 78. 2% , 86. 8% , 84. 1% and 88. 3% , respectively. There was a strong positive correlation between the length of humerus, femur and tibia and the ultimate load (R= 0. 904, 0. 897, 0. 814, P<0. 05). The diameters of humerus, femur and tibia were strongly positively correlated with the ultimate load (R = 0. 759, 0. 814 and 0. 745, P<0. 05). Conclusions The ultimate loads of humerus, femur and tibia in male rats increased first and then decreased with age, and were positively correlated with age before 52 weeks, which could be used for age inference. The highest accuracy of age estimation was ultimate loads of three bones, followed by femur. The length/ middle diameter of humerus, femur and tibia were strongly positively correlated with the ultimate load.

Discussions on Academician TONG Xiaolin's “Three-level Two-node and Three-segment Holographic Theory” / 中医杂志

This paper reviewed the development of biological holography theory， discussed on the limitations of biological holography law， and explained the theoretical connotation and basis of the “three-level two-node and three-segment holographic theory” innovatively proposed by Academician TONG Xiaolin， aiming at inspiring new thinking on the theoretical research of biological holography. By observing the human body structure， Academician TONG Xiaolin finds that there is a similar law in the head， trunk， limbs， and fingers （toes） that there are two moveable joints （groups） dividing the part into three segments， and each segment contains all the information of the whole part， which is a holographic phenomenon. Accordingly， Academician TONG creatively put forward the “three-level two-node and three-segment holographic theory” of the human body， and “three levels” respectively refer to the original level trunk， the branch level limbs， and the end level extremities. The “two nodes” refer to the two joints （groups） of each level， and “two nodes” can be further divided into “three segments”. Therefore， there are “two nodes” and “three segments” in each level with a similar distribution pattern， which reflects the holographic distribution law that the part reflects the whole and the whole includes the part.

Efficacy and Prognostic Factors of Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors.@*METHODS@#Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed.@*RESULTS@#The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024).@*CONCLUSION@#Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.

Comparison of clinical effects of minimally invasive femoral head replacement and proximal femoral nail antirotation in the treatment of comminuted intertrochanteric fracture in the elderly / 中国骨伤

OBJECTIVE@#To analyze the clinical effect of minimally invasive femoral head replacement and proximal femoral nail antirotation(PFNA) internal fixation at the same time in the treatment of elderly patients with comminuted intertrochanteric fracture.@*METHODS@#From April 2020 to October 2020, 76 elderly patients with comminuted intertrochanteric fracture treated by minimally invasive femoral head replacement and PFNA were analyzed retrospectively. There were 35 patients in the prosthetic group, including 24 females and 11 males with an average age of (86.2±6.1) years old. There were 41 patients in PFNA group including 28 females and 13 males with an average age of (84.6±5.3) years old. The operation time, intraoperative blood loss, postoperative ambulation time, hospitalization time and complications were observed and compared between two groups. Harris hip score was performed at 1, 6 and 12 months after operation.@*RESULTS@#All patients were followed up for 13 to 17 months with an average of (14.3±1.4) months. The operation time of the prosthesis group was longer than that of the PFNA group (P<0.05);the amount of bleeding in PFNA group was less than that in prosthesis group (P>0.05);the time of ambulation in prosthetic group was earlier than that in PFNA group(P<0.05);the number of complications in the prosthesis group was less than that in the PFNA group(P<0.05); the Harris score of prosthesis group was significantly higher than that of PFNA group at 1 and 6 months after operation (P<0.05), but there was no significant difference in Harris score between two groups at 12 months after operation(P>0.05);the number of complications in the prosthesis group was less than that in the PFNA group (P<0.05).@*CONCLUSION@#Minimally invasive femoral head replacement is a good choice for the elderly patients with commuited intertrochanteric fracture. It can improve the quality of life and reduce the burden of family members and society.

One case of developmental epileptic encephalopathy caused by NR4A2 gene variation and literature review / 中华神经科杂志

Objective:To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation, and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease. Methods:The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected, video electroencephalogram, craniocerebral magnetic resonance imaging and family whole exon sequencing were improved, and the suspected mutation sites were verified by Sanger sequencing. Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene. Results:It was found that there was a heterozygous missense mutation at the locus c.866G>A (p.A289H) of NR4A2 gene in the child, which was a de novo mutation, and both parents were wild type. According to the American Society of Medical Genetics and Genomics variation classification, it was assessed as a suspected pathogenic variation. Through literature review, there were 16 related cases reported internationally, with clinical phenotypes including mental retardation/mental retardation, language disorders, seizures, muscle tone changes and different psychological and behavioral problems. Conclusions:The NR4A2 gene is not only associated with dopa responsive disorders, but also with neurological development, intellectual impairment, language development delay, and epilepsy. The mutation of NR42A gene c.866G>A (p.A289H) is the genetic cause of the patient, and the detection of this locus expands the NR4A2 gene spectrum. NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.

Multi-section ultrasonic diagnosis and classification of congenital clubfoot / 中华超声影像学杂志

Objective:To evaluate and analyze the ultrasonic findings of idiopathic clubfoot and positional clubfoot deformities.Methods:Forty-nine newborn babies with congenital clubfoot were examined in the Department of Ultrasound of the Third Affiliated Hospital of Zhengzhou University from December 2020 to January 2022, Including 21 newborn babies(32 feet) with idiopathic clubfoot, and 28 babies(53 feet) with positional clubfoot. Twenty-two normal infants in the same period and the normal feet of the single clubfoot were selected as control group. The distance between medial malleolus and scaphoids of all feet were measured by ultrasound. The distance from the tangent line of the lateral edge of calcaneus to the midpoint of the lateral edge of the chondroid bone, medial soft tissue thickness and tibial calcaneal angle were measured by ultrasound. The data of idiopathic clubfoot group, positional clubfoot group and control group were statistically analyzed.Results:A total of 71 newborn babies with 142 feet were evaluated.The idiopathic clubfoot group had born and joint changes in the medial, lateral and posterior side, and the differences were statistically significant compared with the control group (all P<0.05). Compared with the control group, there were statistically significant differences in the medial and lateral side of the positional group(all P<0.05). But no significant changes in the posterior side( P>0.05). There were significant differences between medial and posterior side of idiopathic and positional clubfoot group (all P<0.05), but no significant differences in lateral side ( P>0.05). Conclusions:Ultrasonography can clearly display the tarsus bones in clubfoot, and observe the deformity changes of the idiopathic clubfoot and positional clubfoot.

Analysis of induced radiation and shielding materials in proton therapy room / 中国辐射卫生

Objective To analyze the dose distribution of induced radiation in fixed proton beam therapy room and the influence of shielding materials, and to provide a basis for radiation protection and shielding material selection in proton therapy. Methods FLUKA was used to simulate the dose distribution of induced radiation in fixed proton beam therapy room, the dose over time, and the influence of different concrete materials. Results The dose of induced radiation was mainly concentrated around the target, and the dose rapidly decreased to 1/5-1/10 of the value at the time of stopping irradiation after cooling for 3-5 min. The induced radiation in concrete formed a slightly higher dose area at the end of the main beam near the inner side of the shield. The content of Fe, O, and H in concrete had significant effects on induced radiation (P < 0.01), and the dose was negatively correlated with the content of Fe. Conclusion The patients after proton therapy as well as the induced radiation in air and shielding materials are the main sources of external radiation dose for workers, and waiting for a period of time is the most effective way to protect the staff. Without considering the difficulty in construction and based on the analysis of shielding materials in protection against external irradiation and their influence on induced radiation, heavy concrete with a relatively high level of Fe is the best choice of the shielding material for proton therapy room.

[Immunophenotypic Features and Clinical Prognosis of Patients with Mixed Phenotype Acute Leukemia].

OBJECTIVE: To retrospectively analyze the laborotary test results and clinical data of 31 patients with mixed phenotype acute leukemia (MPAL) in order to summarize and discuss the biological characteristics, curative effect, and prognosis of each subtype of MPAL based on immunophenotype results. METHODS: MPAL patients diagnosed and treated in our hospital from July 2013 to January 2019 were selected to analyze the data of cell morphology, immunophenotyping, cytogenetics, molecular biology (MICM), and routine blood at initial diagnosis. Follow-up was carried out until the last discharge time. RESULTS: Among 31 patients, there were 19 males and 12 females, with a median age of 41(12-76) years old. According to the results of immunophenotyping and EGIL score, there were 16 cases of myeloid-T lymphoid mixed phenotype (myeloid-T group), 9 cases of myeloid-B lymphoid mixed phenotype (myeloid-B group), 5 cases of T-B lymphoid mixed phenotype (T-B group), and 1 case of myeloid-T-B lymphoid mixed phenotype. Compared between different subtypes, the antigen expression characteristics were the highest positive rate and expression rate of HLA-DR in myeloid-B group, and the positive rate of CD2 in T-B group was significantly higher than that in the myeloid-T group. Meanwhile, the expression rates of CD7 and cCD3 (cytoplasmic CD3) in T-B group were higher than those in myeloid-T group, and cCD79a was positive in all cases of myeloid-B group and T-B group. The median WBC of T-B group was 81.92×109/L, which was significantly higher than that of the other two groups (P<0.05). The quantitative results of WT1 were higher than 10-4 in 92.6% of the patients, and the WT1 expression level in myeloid-B group was significantly lower than the other two groups (P<0.01). Among the 9 patients with myeloid-B mixed phenotype, 5 cases showed BCR-ABL positive. Among 28 patients followed up, 21 cases achieved complete remission (CR), the median time to first obtain CR was 32.5(9-75) days, and the median follow-up time was 16 months (range from 21 days to 6 years). The CR rate and median overall survival (OS) time in myeloid-B group were 88.9% and 40 months, which were higher than the other two groups. The CR rate and 3-year OS rate in T-B group were relatively lower (50.0%, 0). CONCLUSION: WT1 gene is highly expressed in patients with MPAL, and each subgroup of MPAL based on immuophenotype has its unique antigen expression characteristics. Compared with myeloid-T group and T-B group, myeloid-B group can acquire higher remission rate and have better prognosis.

Overlapping syndrome of recurrent anti-N-methyl-D-aspartate receptor encephalitis and anti-myelin oligodendrocyte glycoprotein demyelinating diseases: A case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (NMDARe) is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease, whereas it has been relatively rare. We describe a man with no history of tumor who successively developed anti-NMDARe and anti-myelin oligodendrocyte glycoprotein antibody disease. CASE SUMMARY: A 29-year-old man was initially admitted with headache, fever, intermittent abnormal behavior, decreased intelligence, limb twitching and loss of consciousness on July 16, 2018. On admission, examination reported no abnormality. During his presentation, he experienced aggravated symptoms, and the re-examination of cranial magnetic resonance imaging (MRI) indicated punctate abnormal signals in the left parietal lobe. External examination of cerebrospinal fluid and serum results revealed serum NMDAR antibody (Ab) (-), cerebrospinal fluid NMDAR-Ab (+) 1:10 and Epstein-Barr virus capsid antigen antibody IgG (+). Due to the imaging findings, anti-NMDARe was our primary consideration. The patient was treated with methylprednisolone and gamma globulin pulse therapy, mannitol injection dehydration to reduce intracranial pressure, sodium valproate sustained-release tablets for anti-epilepsy and olanzapine and risperidone to mitigate psychiatric symptoms. The patient was admitted to the hospital for the second time for "abnormal mental behavior and increased limb movements" on December 14, 2018. Re-examination of electroencephalography and cranial MRI showed no abnormality. The results of autoimmune encephalitis antibody revealed that serum NMDAR-Ab was weakly positive and cerebrospinal fluid NMDAR-Ab was positive. Considering comprehensive recurrent anti-NMDARe, the patient was treated with propylene-hormone pulse combined with immunosuppressive agents (mycophenolate mofetil), and the symptoms were relieved. The patient was admitted for "hoarseness and double vision" for the third time on August 23, 2019. Re-examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe, and synoptophore examination indicated concomitant esotropia. The patient's visual acuity further decreased, and the re-examination of cranial MRI + enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata, left pons arm, left cerebellum and right midbrain, thalamus. The patient was diagnosed with an accompanying demyelinating disease. Serum anti-myelin oligodendrocyte glycoprotein 1:10 and NMDAR antibody 1:10 were both positive. The patient was diagnosed with myelin oligodendrocyte glycoprotein antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome. The patient was successfully treated with methylprednisolone, gamma globulin pulse therapy and rituximab treatment. The patient remained asymptomatic and follow-up MRI scan 6 mo later showed complete removal of the lesion. CONCLUSION: We emphasize the rarity of this antibody combination and suggest that these patients may require longer follow-up due to the risk of recurrence of two autoimmune disorders.

The stereoselective conversion of epimerized alkoxyl phosphine-borane to P,C, axial-stereogenic tertiary phosphine via cleavage of P-O bond.

The P-O bond of epimerized alkoxyl phosphine-borane was cleaved by naphthalene-lithium, to form two diastereomers of P-anions in a ratio of 86 : 14, which was then converted to secondary phosphine-borane via acidification, and to tertiary phosphines with alkyl halides with enhanced 96 : 4 dr. The isolated tertiary phosphine containing hydroxyl (in >99 : 1 dr) was converted to multi-stereogenic tertiary phosphines via O-alkylation with alkylene dihalides.

Exploration and practice of holistic medicine and integrated medicine in the teaching of forensic pathological cause analysis of deaths / 中华医学教育探索杂志

Based on the characteristics of forensic pathology, this paper explains the concept, connotation and advantages of holistic medicine and integrated medicine in the teaching of forensic pathology. Then, through the introduction of the specific teaching process design and effect analysis of the death cause analysis practical cases, it clarifies the necessity and effectiveness of integrated medicine and holistic medicine in the teaching of forensic pathology, and provides new ideas for the reform of the overall teaching of forensic pathology.

Clinical effect of tenofovir alafenamide fumarate on chronic hepatitis B patients with low viral load after entecavir treatment / 临床肝胆病杂志

Objective To investigate the clinical effect of tenofovir alafenamide fumarate (TAF) on chronic hepatitis B (CHB) patients with low-level viremia (LLV) after entecavir (ETV) treatment. Methods A total of 160 CHB patients who received ETV antiviral therapy in Wuhan Jinyintan Hospital from March 2019 to October 2020 were enrolled and divided into experimental group and control group by propensity score matching, with 80 patients in each group. The patients in the experimental group were given TAF antiviral therapy, and those in the control group were given ETV treatment; the course of treatment was 24 weeks for both groups. The two groups were compared in terms of HBV-DNA clearance rate, HBeAg clearance rate, alanine aminotransferase (ALT) level, estimated glomerular filtration rate (eGFR), FIB-4 value, liver stiffness measurement, and adverse drug reactions after treatment. The t -test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Results After 24 weeks of treatment, compared with the control group, the experimental group had significantly higher HBV DNA clearance rate (96.25% vs 16.25%, χ 2 =104.03, P 0.05). Conclusion For CHB patients with LLV after ETV treatment, the change to TAF antiviral therapy can effectively increase their HBV DNA clearance rate and HBeAg clearance rate, improve liver and renal function, and reduce the degree of liver fibrosis, with good safety.

Research and development of intelligent medical equipment and internationalization of acupuncture and moxibustion: thoughts from researchers of acupuncture robot / 中国针灸

Under the background of artificial intelligence, the internationalization of acupuncture and moxibustion has braced an important opportunity. Intelligent medical equipment for acupuncture and moxibustion has entered from the laboratory into the clinic. However, the current research focuses on optimizing acupuncture treatment technology rather than innovating acupuncture theory. Internationally, the westernization of traditional acupuncture and the dilution of its characteristics are worrying. It is urgent to promote the China-led international standards of acupuncture and moxibustion and the patent protection of traditional acupuncture and moxibustion. Intelligent medical equipment will play the role of media, and promote the internationalization of traditional acupuncture and moxibustion with standardized and highly-integrated intelligent medical equipment for acupuncture and moxibustion, and integrate modern scientific and technological achievements. It is a feasible way for the internationalization of acupuncture and moxibustion.

Analysis of acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack based on complex network / 中国针灸

Acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack was analyzed based on complex network, acupoint names and indications were extracted from the book, which provided ideas and methods for promoting the modernization of acupuncture and moxibustion by using complex network technology. A total of 112 acupoints in 201 acupuncture prescriptions were included, and the total frequency of acupoints was 880 times, forming 42 034 acupoint pairs. In terms of network indexes, compared with the complex network of comprehensive acupuncture books, such as Meridian and Acupoint Science, Zhenjiu Dacheng, Acupuncture A and B Meridians formed based on the same mathematical method, the complex network model for CHENG Dan-an's Note About Treatise on Cold-Attack shows more typical small world effect, which is characterized by higher network density (6.762) and shorter average path length (1.064). This phenomenon may be related to the tongue and pulse which added the link between acupoints. For the node indexes, the analysis of topological indexes such as Page Rank shows that acupoints represented by Dazhui (GV 14) has higher compatibility value in the treatment of exogenous diseases, which further demonstrates the clinical value of eigenvector centrality in guiding intelligent compatibility of points.

Predictors of infliximab-induced deep remission in treatment-naïve patients with isolated small bowel Crohn's disease.

OBJECTIVES: Deep remission should be induced early in the disease course of Crohn's disease (CD), because it significantly prevents disease progression. Identifying predictors of deep remission before treatment is important to guide therapeutic strategy. Little is known about the predictors of infliximab-induced deep remission in treatment-naïve patients with isolated small bowel CD. We aimed to investigate the predictors of infliximab-induced deep remission in these patients. MATERIALS AND METHODS: From January 2015 to December 2019, all consecutive treatment-naïve patients with isolated small bowel CD who started infliximab induction therapy (5 mg/kg at week 0, 2, and 6) and underwent capsule endoscopy (CE) at week 14 were retrospectively included. Deep remission was defined as clinical remission in combination with CE-identified mucosal healing. Logistic regression was used to investigate the predictors of 14-week deep remission. RESULTS: Ninety-one patients were included. At week 14 after infliximab induction therapy, deep remission was found in 42 patients. Multivariate logistic regression analysis showed that a moderate-to-severe endoscopic disease [odds ratio (OR), 0.28; p = .01] and the presence of fibrofatty proliferation (OR, 0.26; p = .04) at baseline were independently associated with a decreased possibility of deep remission. CONCLUSIONS: In treatment-naïve patients with isolated small bowel CD, a moderate-to-severe endoscopic disease and the presence of fibrofatty proliferation at baseline reduce the possibility of infliximab-induced deep remission. Patients with such risk factors may need more aggressive treatment at the beginning of induction therapy to promote deep remission at an early stage.

Comparison of heat-inactivated and infectious SARS-CoV-2 across indoor surface materials shows comparable RT-qPCR viral signal intensity and persistence

Environmental monitoring in public spaces can be used to identify surfaces contaminated by persons with COVID-19 and inform appropriate infection mitigation responses. Research groups have reported detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on surfaces days or weeks after the virus has been deposited, making it difficult to estimate when an infected individual may have shed virus onto a SARS-CoV-2 positive surface, which in turn complicates the process of establishing effective quarantine measures. In this study, we determined that reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection of viral RNA from heat-inactivated particles experiences minimal decay over seven days of monitoring on eight out of nine surfaces tested. The properties of the studied surfaces result in RT-qPCR signatures that can be segregated into two material categories, rough and smooth, where smooth surfaces have a lower limit of detection. RT-qPCR signal intensity (average quantification cycle (Cq)) can be correlated to surface viral load using only one linear regression model per material category. The same experiment was performed with infectious viral particles on one surface from each category, with essentially identical results. The stability of RT-qPCR viral signal demonstrates the need to clean monitored surfaces after sampling to establish temporal resolution. Additionally, these findings can be used to minimize the number of materials and time points tested and allow for the use of heat-inactivated viral particles when optimizing environmental monitoring methods. ImportanceEnvironmental monitoring is an important tool for public health surveillance, particularly in settings with low rates of diagnostic testing. Time between sampling public environments, such as hospitals or schools, and notifying stakeholders of the results should be minimal, allowing decisions to be made towards containing outbreaks of coronavirus disease 2019 (COVID-19). The Safer At School Early Alert program (SASEA) [1], a large-scale environmental monitoring effort in elementary school and child care settings, has processed > 13,000 surface samples for SARS-CoV-2, detecting viral signals from 574 samples. However, consecutive detection events necessitated the present study to establish appropriate response practices around persistent viral signals on classroom surfaces. Other research groups and clinical labs developing environmental monitoring methods may need to establish their own correlation between RT - qPCR results and viral load, but this work provides evidence justifying simplified experimental designs, like reduced testing materials and the use of heat-inactivated viral particles.

Automated, miniaturized, and scalable screening of healthcare workers, first responders, and students for SARS-CoV-2 in San Diego County

BackgroundSuccessful containment strategies for SARS-CoV-2, the causative virus of the COVID-19 pandemic, have involved widespread population testing that identifies infections early and enables rapid contact tracing. In this study, we developed a rapid and inexpensive RT- qPCR testing pipeline for population-level SARS-CoV-2 detection, and used this pipeline to establish a clinical laboratory dedicated to COVID-19 testing at the University of California San Diego (UCSD) with a processing capacity of 6,000 samples per day and next-day result turnaround times. Methods and findingsUsing this pipeline, we screened 6,786 healthcare workers and first responders, and 21,220 students, faculty, and staff from UCSD. Additionally, we screened 6,031 preschool-grade 12 students and staff from public and private schools across San Diego County that remained fully or partially open for in-person teaching during the pandemic. Between April 17, 2020 and February 5, 2021, participants provided 161,582 nasal swabs that were tested for the presence of SARS-CoV-2. Overall, 752 positive tests were obtained, yielding a test positivity rate of 0.47%. While the presence of symptoms was significantly correlated with higher viral load, most of the COVID-19 positive participants who participated in symptom surveys were asymptomatic at the time of testing. The positivity rate among preschool-grade 12 schools that remained open for in-person teaching was similar to the positivity rate at UCSD and lower than that of San Diego County, with the children in private schools being less likely to test positive than the adults at these schools. ConclusionsMost schools across the United States have been closed for in-person learning for much of the 2020-2021 school year, and their safe reopening is a national priority. However, as there are no vaccines against SARS-CoV-2 currently available to the majority of school-aged children, the traditional strategies of mandatory masking, physical distancing, and repeated viral testing of students and staff remain key components of risk mitigation in these settings. The data presented here suggest that the safety measures and repeated testing actions taken by participating healthcare and educational facilities were effective in preventing outbreaks, and that a similar combination of risk-mitigation strategies and repeated testing may be successfully adopted by other healthcare and educational systems.