Obesity phenotype induced by high-fat diet promotes diethylnitrosamine (DEN)-induced precancerous lesions by M1 macrophage polarization in mice liver.

Liver precancerous lesions are the key to improving the efficacy of cancer treatment because of the extremely poor prognosis of HCC patients in moderate and late stages. Obesity-related HCC progression is closely related to the inflammatory microenvironment, in which macrophages are one of the major constituents. In the present study, we ask whether obesity promotes diethylnitrosamine (DEN)-induced precancerous lesions by M1 macrophage polarization. First, an association between obesity and liver precancerous lesions was determined by histopathological observations, immunochemistry and immunoblotting. The characteristics of early precancerous lesions (trabecular thickening) appeared earlier eight weeks in obese mice than in normal diet mice after DEN induction. The glutathione S-transferase placental-1 (Gstp 1) and alpha-fetoprotein (AFP) expression in obese mice after DEN induction was higher than that in the same period after DEN injection in normal diet mice. Furthermore, there was a significant increase in the total macrophage number (F4/80+) of DEN and M1 macrophage number (CD86+F4/80+) in obese mice compared with that in normal diet mice. Besides, the expressions of four pro-inflammatory factors in DEN-induced obese mice were significantly higher compared with that in normal diet mice. Additionally, angiogenesis was revealed by immunostaining assay to be associated with the inflammatory response. All the results demonstrate that obesity promotes DEN-induced precancerous lesions by inducing M1 macrophage polarization and angiogenesis.

SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant

Recent studies have revealed the unique virological characteristics of Omicron, the newest SARS-CoV-2 variant of concern, such as pronounced resistance to vaccine-induced neutralizing antibodies, less efficient cleavage of the spike protein, and poor fusogenicity. However, it remains unclear which mutation(s) in the spike protein determine the virological characteristics of Omicron. Here, we show that the representative characteristics of the Omicron spike are determined by its receptor-binding domain. Interestingly, the molecular phylogenetic analysis revealed that the acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidate that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue in another protomer in the spike trimer, which confers the attenuated spike cleavage efficiency and fusogenicity of Omicron. Our data shed light on the evolutionary events underlying Omicron emergence at the molecular level. HighlightsO_LIOmicron spike receptor binding domain determines virological characteristics C_LIO_LISpike S375F mutation results in the poor spike cleavage and fusogenicity in Omicron C_LIO_LIAcquisition of the spike S375F mutation triggered the explosive spread of Omicron C_LIO_LIF375-H505-mediated {pi}-{pi} interaction in the spike determines the phenotype of Omicron C_LI

Application and evaluation of matrix-assisted laser desorption ionization time-of-flight mass spectrometry in environmental pollution investigation of blood collection and supply institutions / 中国输血杂志

【Objective】 To investigate the environmental pollution of blood collection and supply institutions by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and evaluate its application value. 【Methods】 Colonies of air from blood donation sites, skin puncture sites of blood donors, platelet storage boxes, platelet collection equipment, object surfaces of related experimental consumables and cuff surfaces of staff after disinfection were collected, and typical colonies after cultivation were selected for microbial identification by microbial mass spectrometry and then compared with bacteria results detected in blood components from May 2017 to May 2021. 【Results】 Aseptic growth, the number of colonies ≤4.0 CFU/ dish, and the number of colonies > 4.0 CFU/dish accounted for 21.20%, 62.20% and 16.60%, respectively. The qualified rate from high to low was platelet storage box, bacteria settling in the air of blood donation room after disinfection, platelet collection equipment, skin puncture site of blood donors after disinfection, the surface of platelet consumables and the surface of medical staff's overalls. After disinfection, the blood donors' skin puncture sites were compared with other collection sites, and the t values were 2.0371, 1.508, 2.109, 1.961 and 1.778, respectively, with no significant difference (P>0.05). Thirty cases of bacterial contamination of blood components were detected from May 2017 to May 2021, among which the detection rate of apheresis platelets was the highest, and the t values were 1.731 and 2.272, relative to the contamination frequency of erythrocytes and plasma bacteria (P>0.05), while the t value was 2.875, relative to concentrated platelets, with significant difference (P<0.05). 【Conclusion】 Bacterial contamination of blood components mostly come from air bacteria settling, blood donors' arms and skin after disinfection, and surfaces of related equipment and materials. Therefore, it is of clinical significance to conduct strict disinfection of working sites, establish disinfection monitoring methods and formulate disinfection hygiene standards in blood stations.

SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance

SARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the insertion of the RSYLTPGD246-253N mutation is closely associated with the massive infection spread of the Lambda variant in South America. HighlightsO_LILambda S is highly infectious and T76I and L452Q are responsible for this property C_LIO_LILambda S is more susceptible to an infection-enhancing antibody C_LIO_LIRSYLTPGD246-253N, L452Q and F490S confer resistance to antiviral immunity C_LI Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

SARS-CoV-2 spike P681R mutation enhances and accelerates viral fusion

During the current SARS-CoV-2 pandemic, a variety of mutations have been accumulated in the viral genome, and currently, four variants of concerns (VOCs) are considered as the hazardous SARS-CoV-2 variants to the human society1. The newly emerging VOC, the B.1.617.2/Delta variant, closely associates with a huge COVID-19 surge in India in Spring 20212. However, its virological property remains unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic, and notably, more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates the spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than the parental virus. Our data suggest that the P681R mutation is a hallmark that characterizes the virological phenotype of the B.1.617.2/Delta variant and is closely associated with enhanced pathogenicity.

Achievements of occupational health under the leadership of CPC / 环境与职业医学

Since its founding 100 years ago, the Communist Party of China (CPC) has attached great importance to the occupational health of workers, and closely linked the safeguard of occupational safety and health of workers with the missions of leading the people to stand up, get rich, and become strong. Based on this, the achievements of occupational health work made under the leadership of the CPC since the new democratic revolution, socialist revolution and construction, the new period of reform and opening up and socialist modernization, and socialism with Chinese characteristics for a new era were summarized, so as to provide reference for understanding the legacy of China's occupational health undertaking, and innovating to create the future.

SARS-Cov-2-, HIV-1-, Ebola-neutralizing and anti-PD1 clones are predisposed

Antibody repertoire refers to the totality of the superbly diversified antibodies within an individual to cope with the vast array of possible pathogens. Despite this extreme diversity, antibodies of the same clonotype, namely public clones, have been discovered among individuals. Although some public clones could be explained by antibody convergence, public clones in naive repertoire or virus-neutralizing clones from not infected people were also discovered. All these findings indicated that public clones might not occur by random and they might exert essential functions. However, the frequencies and functions of public clones in a population have never been studied. Here, we integrated 2,449 Rep-seq datasets from 767 donors and discovered 5.07 million public clones - ~10% of the repertoire are public in population. We found 38 therapeutic clones out of 3,390 annotated public clones including anti-PD1 clones in healthy people. Moreover, we also revealed clones neutralizing SARS-CoV-2, Ebola, and HIV-1 viruses in healthy individuals. Our result demonstrated that these clones are predisposed in the human antibody repertoire and may exert critical functions during particular immunological stimuli and consequently benefit the donors. We also implemented RAPID - a Rep-seq Analysis Platform with Integrated Databases, which may serve as a useful tool for others in the field.

Rational molecular targeting of the inter-subunit interaction between human cardiac troponin hcTnC and hcTnI using switch peptide-competitive biogenic medicines.

The human cardiac troponin (hcTn) has been implicated in diverse cardiovascular diseases (CDs). The protein function is regulated by the inter-subunit interaction between the N-terminal domain of hcTnC and the C-terminal switch peptide of hcTnI; disruption of the interaction has been recognized as a potential therapeutic strategy for CDs. Here, we report use of biogenic medicines as small-molecule competitors to directly disrupt the protein-protein interaction by competitively targeting the core binding site (CBS) of hcTnC NTD domain. A multistep virtual screening protocol is performed against a biogenic compound library to identify competitor candidates and competition assay is employed to verify the screening results. Consequently, two compounds Collismycin and Compound e are identified as strong competitors (CC50 < 10 µM) with hcTnI for hcTnC CBS site, while other tested compounds are found to have moderate (CC50 = 10-100 µM), low (CC50 > 100 µM) or no (CC50 = N.D.) potency. The competitor ligands are anchored at the core groove of hcTnC CBS site through aromatic and hydrophobic interactions, while few peripheral hydrogen bonds are formed to further confer specificity for domain-compound recognition. These molecular-level findings would benefit from further in vitro and in vivo studies at cellular and animal levels, which can help to practice the ultimate therapeutic purpose.

Clinical analysis of 256 cases of facial plastic surgery in maxillofacial trauma / 中国基层医药

Objective To investigate the experience and effect of emergency cosmetic surgery for maxillofacial trauma.Methods From April 2011 to March 2017,256 patients with maxillofacial trauma in emergency cosmetic surgery in the People's Hospital of Lezhi County were selected in the study.The causes,locations,treatment methods and clinical effects were analyzed.Results In 256 cases,125 cases of traffic accident injury,68 cases of agricultural and industrial injury,48 cases of accidental injury,13 cases of asfights,2 cases of animal bites;of which 121 cases of lower face,73 cases of midface,39 cases of midface and lower face together,23 cases of upper face;98 cases of maxillofacial region fracture;105 patients had different degree of soft tissue defect.All patients the wound healed in primary healing,after stitches the wound healing in good contraposition,surface leveling,scar slender,facial features did not change significantly,no complications were observed.After 3-6 months of follow-up,the scar was not obvious and the appearance was satisfactory.Conclusion The clinical effect of emergency cosmetic surgery for maxillofacial trauma is satisfactory.Emergency cosmetic surgery can be used as an emergency treatment for maxillofacial trauma in primary hospital.

Gene expression analysis of neoadjuvant chemotherapy efficacy in human breast cancers / 军事医学

Objective To analyze gene expression profiles of biopsy specimens from breast cancer patients who were treated with neoadjuvant chemotherapy(NAC) after biopsies, and to identify the genes which are closely associated with the efficacy of neoadjuvant chemotherapy with T/FAC [docetaxel(Taxotere), 5-fluorouracil, doxorubicin and cyclophosphamide] or T/FEC (Taxotere, 5-fluorouracil, epirubicin and cyclophosphamide) regimen.Methods We retrieved and collected gene expression profiles from publicly available databases.Four datasets, a total of 844 samples, were finally retained because all the patients had received a uniform neoadjuvant chemotherapy regimen.Response to neoadjuvant chemotherapy was categorized as a pathological complete response (pCR) or residual invasive cancer (RD).The differentially expressed genes (adjusted P-value<0.05) and therapeutic efficacy were analyzed and explored.Results After differential analysis, genes whose expressions were higher or lower in pCR group than in RD group were identified in each of the four datasets, respectively.There were 34 and 42 genes which were simultaneously more highly expressed or more lowly expressed in pCR group than in RD group in the four datasets.The unsupervised clustering, based on the 76 intersection genes, showed that the pCR specimens tended to form one cluster and the RD tended to form the other.Conclusion The seventy-six differentially expressed genes are associated with the efficacy of neoadjuvant chemotherapy and are likely to be novel predictive biomarkers for the efficacy of neoadjuvant chemotherapy.

Alveolar bone thickness and root length changes in the treatment of skeletal Class III patients facilitated by improved corticotomy: a cone-beam CT analysis / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the alveolar bone thickness and root length changes of anterior teeth with cone-beam computed tomography (CBCT).</p><p><b>METHODS</b>CBCT scans were taken for 12 skeletal Class III patients who accepted the improved corticotomy (IC) procedures during pre-surgical orthodontics. The CBCT data in T1 (the maxillary dental arch was aligned and leveled) and T2 (extraction space closure) were superimposed and the alveolar bone thickness at root apex level and root length measurements were done.</p><p><b>RESULTS</b>From T1 to T2, the buccal alveolar bone thickness for the upper lateral incisors increased from (1.89±0.83) to (2.47±1.02) mm (P<0.05), and for central incisors and for canines from (2.32±0.71) to (2.68±1.48) mm and from (2.28±1.08) to (2.41±1.40) mm, respectively. According to Sharpe Grading System, the root resorption grade for 69 teeth of 72 was located in Grade 1, two teeth in Grade 2, one tooth in Grade 3.</p><p><b>CONCLUSIONS</b>The improved corticotomy had the potential to increase the buccal alveolar bone thickness and the root resorption in most teeth was in Grade 1 according to Sharpe grading system.</p>

A clinical study of the effect of modified corticotomy on periodontium / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of modified corticotomy on periodontal parameters in the treatment of Class III surgical patients facilitated by accelerated osteogenic orthodontics.</p><p><b>METHODS</b>Nine Class III surgical patients at the age of 18-30 (7 females and 2 males) who were systematically and periodontally healthy were involved in the study, including 72 teeth and 216 sites. The modified corticotomy (piezotome) and bone graft (tricalcium phosphate, TCP) in maxillary anterior area were conducted after aligning and leveling the dental arch to facilitate the closing of space in upper dentition. Measurements such as plaque index (PLI), probing depth (PD), bleeding index (BI), recession (REC), keratinized gingiva width (KEG), biotype (BIO) were recorded pre-operation, 1, 2, 4 and 8 weeks post-operation.</p><p><b>RESULTS</b>The differences of PD, BI and REC before and after operation were not statistically significant (P > 0.05). The median value of PLI before and after operation was 0. The percentage of thin biotype and thick biotype teeth was 74% (53/72) and 26% (19/72) pre-operation respectively. The difference of KEG between pre-operation [(5.1 ± 1.4) mm] and 8 weeks post-operation [(5.1 ± 1.2) mm] was not statistically significant (P = 0.658), but the mean value of KEG in other post-operation groups [1 week: (5.7 ± 1.3) mm, 2 weeks: (5.8 ± 1.3) mm, 4 weeks: (5.6 ± 1.4) mm] was significantly higher than those of pre-operation (F = 12.087, P = 0.000).</p><p><b>CONCLUSIONS</b>Modified corticotomy in the treatment of Class III surgical patients facilitated by accelerated osteogenic orthodontics is safe to periodontium.</p>

Human synovial fluid promotes directed differentiation of bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Nowadays, growth factors are commonly used to induce bone marrow mesenchymal stem cells. However, this is a high-cost method with a great amount of growth factors. In addition, the chondrogenic potential of bone marrow mesenchymal stem cells wil decrease significantly with increasing times of culture. OBJECTIVE:To observe the directed differentiation of bone marrow mesenchymal stem cells co-cultured with human synovial fluid. METHODS:Human bone marrow mesenchymal stem cells were isolated and cultured by adherence screening method. The synovial fluid of the knee was aspirated from healthy volunteers by aseptic operation. Passage 3 human bone marrow mesenchymal stem cells were co-cultured with the fol owing media:synovial fluid+complete medium;synovial fluid+bone marrow mesenchymal stem cells+complete medium;bone marrow mesenchymal stem cells+complete medium. The morphology and growth of the cells were observed under an inverted microscope every day. At days 7, 14 and 21 of induction, toluidine blue staining and immunocytochemical staining were performed. RESULTS AND CONCLUSION:After co-culture with human synovial fluid, human bone marrow mesenchymal stem cells proliferated slowly, and varied from fusiform to oval or polygonal;toluidine blue and col agen II staining were positive. These findings indicate that the synovial fluid has a positive role in the chondrogenic differentiation of bone marrow mesenchymal stem cells. The synovial fluid may contain substances that promote the chondrogenic differentiation of bone marrow mesenchymal stem cells.

Three-dimensional evaluation of the relationship between dental and basal arch forms in skeletal class II malocclusions / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aims to investigate the relationship between the dental and basal arch forms of patients with skeletal class II malocclusion using three-dimensional virtual models and to generate the best-fit curve for these arch forms.</p><p><b>METHODS</b>The mandibular dental casts of 35 skeletal class II patients were taken prior to treatment and were laser scanned. The facial axis (FA) points, which were used to represent the dental arch, and the WALA points, which were used to represent the basal bone, were identified for each tooth from the right first molar to the left first molar. The Pearson correlation coefficients between the intercanine and intermolar widths at the FA and WALA points were determined. Finally, the best-fit curves were generated using the fourth-degree polynomial equation to represent the arch forms.</p><p><b>RESULTS</b>A strong correlation was found between the FA and WALA intermolar widths (r = 0.873). However, a moderate correlation was observed between the FA and WALA intercanine widths (r = 0.534). The difference between the intermolar widths at the FA and WALA points was significant (P < 0.01). No statistically significant difference was found between the intercanine widths (P = 0.481). The radii of curvature of the FA and WALA curves in the anterior teeth area were 15.194 and 20.250, respectively. The regression coefficients of the FA and WALA curves were calculated as R2 = 0.912 and 0.947, respectively.</p><p><b>CONCLUSION</b>For skeletal class II malocclusion patients, the FA and WALA dental intermolar widths showed strong correlation, whereas the FA and WALA intercanine widths exhibited moderate correlation. The FA points were located more labially in the anterior teeth area but more lingually in the posterior teeth area. No statistically significant difference was found between the intercanine FA and WALA widths. The difference between the intermolar widths at the FA and WALA points was significant. The radii of curvature of the FA curve was larger than that of the WALA curve in the anterior teeth area.</p>

Construction of clinical database on pelvic trauma life cycle: a preliminary study / 中华创伤杂志

Objective To construct the clinical database on pelvic trauma life cycle so as to provide reference for epidemiological investigations and development of pelvic damage control plan. Methods The existing pelvic trauma data of the hospital information system was analyzed to discuss the main evaluation indicators and data types at different stages, including basic data, injury severity index, underlying disease, fracture classification, specialist treatment, rehabilitation and follow-up information. Results Based on the V3.0 trauma scoring system, the clinical pelvic trauma ACCESS database was developed. The data of 588 patients with pelvic trauma were collected from November 2007 to May 2009 and preliminarily analyzed. Conclusions Clinical database of pelvic trauma can be used as the specific modules of general network trauma database system and a large-scale, multi-center and standard pelvic trauma database may play an important role in preparation of the prospective damage control plans.

Preliminary studies on repairing osteochondral defects in the rabbit knee joint by using porous PA66/n-HA combination mesenchymal stem cells / 生物医学工程学杂志

We have investigated the effects of repairing knee osteochondral defects in rabbit by using porous polyamide 66/nano-Hydroxyapatite (PA66/n-HA) combination bone marrow mesenchymal stem cells (MSCs). Eighteen 6-month-old New Zealand rabbits were used to produce the models of 4 mm x 4 mm osteochondral defect in the middle trochlea groove of femur. These models were randomly divided into 3 groups: PA66/n-HA + MSCs Group (Group A), PA66/n-HA group (Group B) and Operation control-group (Group C) in which operation for osteochondral defects was performed but neither material nor cells were implanted. The materials in Group A were seeded with MSCs (5 x 10(5)) in vitro before being implanted in to defects. The materials in groups A and B were 0.5 - 0.8 mm lower than normal cartilage. The animals were killed 1 and 4 months after operation. We assessed the effects by means of macroscopic observation, HE staining, toluidine blue staining, immunohistochemistry assay for type I and type II collagen. Group A displayed a little effect at the 1 month, but at the 4th month, Group A showed better results,compared to Groups B and C. At this time point, the repair tissue of Group A was regular; it presented more metachromatic substance visualized by toluidine blue staining, and it expressed type II collagen(+ +) and type I collagen(+). These results demonstrate that the repair tissue in Group A is nearly hyaline cartilage. So we presume that porous PA66/n-HA provides biomechanical support, and at the same time, MSCs enhance the repair effects.

Morphometry of osteoclasts in experimental fracture healing of rabbits / 生物医学工程学杂志

This study was designed to investigate the effects of some Traditional Chinese Medicine (TCM) agents on bone resorption and morphometric features of osteoclasts as well as their relationships. TCM ShengGuZaiZaoSan and XianLingGuBao, were used to treat the experimental fracture. Thirty 6-month-old Chinchilla rabbits were used for the establishment of animal models each with a 3 mm bone defect in the middle of left radius as well as of right radius. These models were divided randomly into 3 groups : ShengGuZaiZaoSan Group (Group A), XianLingGuBao groups (Group B) and control-group (Group C). Every group was further divided into 2 subgroups: a former sacrificed group (14 days after operation) and a latter sacrificed group (31 days after operation). After the rabbits being killed, the samples of their undecalcified calli were subjected to the morphometry study of bone resorption and osteoclasts. Group A had more bone resorption, compared with Group B and C. Both Groups A and B exhibited some changed morphometric features of osteoclasts as compared with Group C (P < 0.05). Simple correlation analysis indicated that bone resorption is mainly correlated with osteoclast numbers, and that in individual group, bone resorption is correlated with osteoclast form factor, area and mean photodensity (P < 0.05). These allow us to conclude that ShengGuZaiZaoSan can increase bone resorption and accelerate bone remodeling by increasing osteoclast numbers at the former stage and can enhance osteoclast function at the latter stage. These changes are beneficial to fracture healing.

Application of percutaneous epididymal sperm aspiration and percutaneous testicle sperm aspiration in the differentiating diagnosis of obstructive and nonobstructive azoospermia / 中国基层医药

Objective To obtain information on the application value of percutaneous epididymal sperm aspiration(PESA) and percutaneous testicle sperm aspiration(PTSA) in the differentiating diagnosis of obstructive and nonobstructive azoospermia.Methods Sperm recovery procedures were done in infertile men with obstructive azoospermia(OA)(n=37) and nonobstructive azoospermia(NOA)(n=28) by PESA or PTSA.Cytological smears were analysed.Results Sperm was found in the 32 epididymides and 5 testicles of OA group and in the 7 epididymides and 11 testicles of NOA group.Sperm counts were significantly different in two groups.Conclusion PESA and PTSA are efficient methods in differentiating OA and NOA.

Treatment of obstructive azoospermic patients by intracytoplasmic injection of epididymal or testicular sperm / 中国医师进修杂志

Objective To review the treatment results of intracytoplasmic injection(ICSI) of epididymal or testicular sperm obtained from 38 obstructive azoospermic patients.Methods Sperm was retrieved by percutaneous epididymal sperm aspiration(PESA) or testicular sperm extraction(TESE).Intracytoplasmic injection was performed.The rates of fertilization and clinical pregnancy were evaluated.Control group was set up in which intracytoplasmic injection was performed using sperm of ejaculation.Results Forty-one treatment cycles were performed in the 38 obstructive azoospermc patients.The rates of fertilization and clinical pregnancy were 73.3% and 53.6%.Thirty-three treatment cycles were done in the 31 ejaculatory ones.The rates of fertilization and clinical pregnancy were 75.1% and 48.4%.No significant difference was seen between the two groups.In the obstructive azoospermia group,22 clinical pregnancies were achieved including 13 live deliveries and 3 ongoing pregnancies and 6 miscarriages.In the ejaculatory group,16 clinical pregnancies were achieved including 10 live deliveries and 5 ongoing pregnancies and 1 miscarriages.Conclusions ICSI with PESA or TESE is an effective method for treatment of obstructive azoospermic patients.