Heralded Three-Photon Entanglement from a Single-Photon Source on a Photonic Chip.

In the quest to build general-purpose photonic quantum computers, fusion-based quantum computation has risen to prominence as a promising strategy. This model allows a ballistic construction of large cluster states which are universal for quantum computation, in a scalable and loss-tolerant way without feed forward, by fusing many small n-photon entangled resource states. However, a key obstacle to this architecture lies in efficiently generating the required essential resource states on photonic chips. One such critical seed state that has not yet been achieved is the heralded three-photon Greenberger-Horne-Zeilinger (3-GHZ) state. Here, we address this elementary resource gap, by reporting the first experimental realization of a heralded 3-GHZ state. Our implementation employs a low-loss and fully programmable photonic chip that manipulates six indistinguishable single photons of wavelengths in the telecommunication regime. Conditional on the heralding detection, we obtain the desired 3-GHZ state with a fidelity 0.573±0.024. Our Letter marks an important step for the future fault-tolerant photonic quantum computing, leading to the acceleration of building a large-scale optical quantum computer.

CT quantification of pulmonary vessels in lung aging.

AIM: To evaluate the effect of aging on pulmonary vessels based on computed tomography (CT) quantification and analyse the correlation between quantitative pulmonary vascular volume and pulmonary function during aging. MATERIALS AND METHODS: A total of 330 healthy adult volunteers, including 161 men (53 aged 20-39 years, 61 aged 40-59 years, and 47 aged ≥60 years) and 169 women (53 aged 20-39 years, 63 aged 40-59 years, and 53 aged ≥60 years) were recruited in this study. AVIEW software was used to quantitatively measure pulmonary vascular volume, including pulmonary total blood vessel volume (TBV) and small blood vessel volume with a cross-sectional area of <5 mm2 (BV5). Pulmonary vascular volume parameters were standardised using the ratio of vascular volume to the body surface area (BSA; TBV/BSA and BV5/BSA). Subsequently, the effect of aging on the pulmonary vessels was analysed. RESULTS: The pulmonary vascular volume parameters TBV/BSA and BV5/BSA of the whole lung, right lung, and left lung decreased significantly with increasing age (p<0.05). Additionally, TBV/BSA and BV5/BSA of the whole lung were higher in men than in women. The declining trend of pulmonary vascular volume was consistent in men and women and increased with age. CONCLUSIONS: The pulmonary vascular volume parameters, TBV/BSA and BV5/BSA, decreased with age and were weakly positively correlated with pulmonary function.

Acromegaly presented with acne vulgaris: a retrospective study with 123 cases.

BACKGROUND: Acne vulgaris is a prevalent skin condition. We have found that some acromegaly patients have acne. However, no study has examined the relationship between acromegaly and acne. OBJECTIVE: To explore prevalence and correlation of adult acne in patients with acromegaly. METHODS: For this cross-sectional study, we collected questionnaires, clinical information, and laboratory test results of acromegaly patients from January 2022 to December 2022 at Huashan Hospital. Of the 133 questionnaires returned, 123 had valid responses. RESULTS: Of the 123 patients with acromegaly enrolled in this study, 54.5% had adult acne. No statistically significant difference was found in prevalence between male and female patients. 61.2% of adult acne patients reported late-onset acne. Late-onset acne patients first developed acne years before acromegaly diagnosis (mean of 5.6 years for male and 4.5 years for female patients). Some acne patients have received traditional anti-acne treatment. Moreover, 31% of the patients reported no improvement, and only 3.5% of patients claimed complete resolution of acne after treatment. Before acromegaly treatment, the prevalence of adult acne was 51.2%, with mild acne accounting for 73.0%, moderate acne accounting for 23.8%, and severe acne accounting for 3.2%. After acromegaly treatment, the prevalence of adult acne was significantly decreased to 37.4% (P = 0.007). An overall decrease in acne severity was noted, with 93.5%, 6.5%, and 0% having mild, moderate, and severe acne, respectively. A total of 83.6% of the patients had self-assessed acne remission, and 33.3% of the patients reported complete acne resolution. However, 9.0% of patients reported that their condition had worsened after acromegaly treatment. After treatment, GH, IGF-1, IGF-1 index, insulin levels, and HOMA-IR decreased significantly in all patients with acromegaly (P < 0.05). Acne remission correlated positively with IGF-1 levels, but not with GH levels. The relationship between acromegaly and acne remains to be elucidated. CONCLUSIONS: Our findings provide preliminary evidence of the high prevalence of adult acne in acromegaly patients, and a high rate of late-onset acne as well. Traditional anti-acne treatments are less effective. Acne could be considerably relieved by treating acromegaly. Acne remission positively correlated with IGF-1 decline as well, which revealed the correlation between acne and IGF-1.

[Associations of blood pressure change with change in foods' intake among adults with mild to moderate hypertension].

Objective: To explore the association between the intake and changes in various types of food and the changes in blood pressure in patients with mild to moderate hypertension. Methods: Mild to moderate hypertension participants with complete baseline and outcome data were included from DECIDE-Diet study, a multicenter, randomized controlled trial. Dietary records and blood pressure measurements at both 7-day run-in (baseline) and 28-day intervention phases were collected for enrolled participants. Blood pressure change was defined as the difference between blood pressure at the end of trial and the baseline blood pressure. Baseline intake of food was the average daily intake during the run-in period, and the intake increment was defined as the difference between the average intake during the trial period and the average intake during the run-in period. After adjusting for age, sex, study center, intervention groups, baseline body mass index (kg/m2), antihypertension medication use, and baseline total calorie intake, a linear regression model was used to analyze the associations of the before-after-intervention change in blood pressure with baseline intake and intake increment of foods. Results: A total of 258 patients with mild to moderate hypertension were included, including 133 males, aged (56.5±9.9) years. (1) After adjusting for confounding factors, there was no significant association between baseline intake of food and baseline blood pressure (all P>0.05). The blood pressure change was negatively associated with baseline intakes of tubers, vegetables, and vegetable oils but positively with baseline intake of meats; and was negatively associated with intake increment of whole grains and fish (all P<0.05). (2) The multiple linear regression analysis showed that baseline intake of vegetables (ß=-0.021, P=0.004), vegetable oils (ß=-0.260, P=0.002), and increment in intake of fish (ß=-0.128, P=0.026) were all significantly associated with changes in systolic blood pressure; baseline intake of vegetables (ß=-0.017, P=0.002), vegetable oils (ß=-0.182, P=0.001), dairy products (ß=0.021, P=0.022), and increment in intake of fish (ß=-0.092, P=0.010) were all significantly associated with changes in diastolic blood pressure. Conclusion: Increasing the intake of whole grains, vegetables, vegetable oils, and fish and decreasing the intake of meat may be beneficial for blood pressure control in patients with mild to moderate hypertension.

[Clinical characteristics of patients with rheumatic diseases and abnormal liver function].

Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

[Risk factors analysis and prediction model establishment of malignant tumor in patients with polymyositis/dermatomyositis].

Objective: To analyze the risk factors of polymyositis/dermatomyositis (PM/DM) complicated with malignant tumor and to construct clinical prediction model. Methods: A total of 427 PM/DM patients, who were admitted to Rheumatism Immunity Branch, the Second Affiliated Hospital, Air Force Medical University from January 1, 2015 to January 1, 2021, were enrolled in the study, including 129 males and 298 females. The mean age was (51.4±12.2) years. The patients were divided into control group (without malignant tumor, n=379) and case group (with malignant tumor, n=48) according to whether they were complicated with malignant tumors. In the two groups, 70% of the patients' clinical data were randomly selected as the training set data, and the remaining 30% were used as the validation set data. The clinical parameters were retrospectively collected, and risk factors of PM/DM complicated with malignant tumor were analyzed by binary logistic regression. R software was used to construct a clinical prediction model for malignant tumors in PM/DM patients using training set data. Validation set data were used to assess the feasibility of the model. The area under the receiver operating characteristic (ROC) curve (AUC), calibration curve and decision curve analysis (DCA) were used to evaluate the predictive ability, accuracy and clinical applicability of the nomogram model. Results: The age of the control group was (50.4±11.8) years, and males accounted for 26.9%(102/379); the age of the case group was (59.1±12.7) years, and the proportion of males was 56.3% (27/48). The proportion of male, age, the positive rate of anti-transcription mediator 1-γ (TIF1-γ) antibody, glucocorticoid therapy resistance, and levels of creatine kinase (CK), carbohydrate antigen 125(CA125) and carbohydrate antigen 199 (CA199) were all higher in the case group than those in control group, while incidence of interstitial lung disease (ILD), arthralgia, Raynaud's phenomenon, serum albumin (ALB) level and lymphocyte (LYM) count were all lower than those in control group (all P<0.05). Binary logistic regression analysis showed that male (OR=2.931, 95%CI: 1.356-6.335), glucocorticoid therapy resistance (OR=5.261, 95%CI: 2.212-12.513), older age (OR=1.056, 95%CI: 1.022-1.091), elevated CA125 (OR=8.327, 95%CI: 2.448-28.319) and positive anti-TIF1-γ antibody (OR=7.529, 95%CI: 2.436-23.270) were risk factors of malignancy in PM/DM patients (all P<0.05); and complicated with ILD (OR=0.261, 95%CI: 0.099-0.689), complicated with arthralgia (OR=0.238,95%CI:0.073-0.779), elevated LYM count (OR=0.267, 95%CI: 0.103-0.691) were protective factors of malignancy in PM/DM patients (all P<0.05). The AUC of ROC curve predicting malignancy in PM/DM patients with the training concentrated prediction model was 0.887 (95%CI: 0.852-0.922), with a sensitivity of 77.9% and a specificity of 86.3%; it was 0.925 (95%CI: 0.890-0.960), 86.5% and 88.0% in the validated centralized prediction model, respectively. The correction curves of the training set and the validation set indicated that the predictive model had good calibration ability. Both the DCA curves of the training set and the validation set showed that the proposed predictive model had good clinical applicability. Conclusions: Older age, male, glucocorticoid therapy resistance, not complicated with ILD and arthralgia, elevated CA125, positive anti-TIF1-γ antibody, decreased LYM count are risk factors for malignancy in PM/DM patients, and the established nomogram model shows good predictive ability.

[Implementation and quality control of human immunodeficiency virus laboratory diagnosis strategy].

The laboratory diagnostic strategy for human immunodeficiency virus (HIV) is a process to accurately detect HIV patients through a combination of available HIV tests. Laboratory tests for HIV infection are mainly serological antibody and antigen testing and HIV RNA testing. With the update of testing reagents, the sensitivity and specificity have improved substantially and the window period of detection has shortened, but there is a risk of false positives. Various guidelines have recommended different diagnostic strategies for different target populations and different prevalence regions to guide patients to confirm the diagnosis and receive standardized antiretroviral therapy as early as possible. How to refer to the diagnostic strategies, reduce false positives and shorten the window period while increasing the detection rate is an urgent issue for laboratories to address. This article describes the characteristics and advantages and disadvantages of testing methods related to HIV infection from the perspective of laboratory diagnostic strategies, as well as the impact of the development of treatments on diagnostic strategies, in order to provide theoretical support for the practical application of HIV diagnostic strategies.

[A follow-up study on the pain changes trend and effects in patients diagnosed with herpes zoster in Beijing City].

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q1, Q3) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.

[More attention for high-risk pathological features for stage â ¡ colorectal cancer required].

Stage Ⅱ (T3-4N0M0) accounts for 25% of colorectal cancer and five-year survival is between 70% and 80%. However, 25% of patients develop distant metastases and have a survival rate similar to that of stage Ⅲ disease. However, whether or not to give adjuvant chemotherapy is still a controversial issue. As a result, there has been a lot of interest in the identification of the pathological factors underlying the poor prognosis associated with this stage, in order to establish a firmer basis for the administration of adjuvant chemotherapy. But not all high-risk factors are equal for stage Ⅱ colorectal cancer, variability still exists in the management and outcomes of high-risk patients. Here be introduced and commented on thinking and understanding about its controversy and evolution for the attention of the working pathologist and gastroenterologist doctors.

Helical micro-swimmer: hierarchical tail design and propulsive motility.

Helical micro-swimmers have markedly extended the reach of human beings in numerous fields, ranging from in vitro tasks in lab-on-a-chip to in vivo applications for minimally invasive medicine. The previous studies on the propulsive motility optimization of the micro-swimmers mainly focused on the distinct actuation principles (e.g., chemically powered, magnetic- or ultrasound energy-driven) and paid little attention to the structural design of these swimming machines themselves. The improvements of the structures can assist the externally powered motors in providing propulsion in a tiny scale and satisfy the agile locomotion demands. This paper presents the design, mechanics modeling and available experiments of a novel type of hierarchical helical swimming robot that significantly enhances the motility of the helix-based swimmers. Validated by the resistive force theory, our numerical model can well analyze the mechanical properties with a variety of geometric parameters. The motion performance of the hierarchical and conventional helical structures in low Reynolds regimes is presented, highlighting the advantages of hierarchical swimmers over the existing typical swimmers. In addition, the stability and resilience of the hierarchical swimmers can be maintained at a decent level. Moreover, the variable forward velocity resulting from the combined hierarchical structures is investigated here, which can thereby serve as a reliable design strategy. The proposed hierarchical helical design enables enticing opportunities for various device systems of medical robots and bio-integrated electronics.

Optimising diffusion-weighted imaging of the thyroid gland using dedicated surface coil.

AIM: To assess the feasibility of applying field-of-view (FOV) optimised and constrained undistorted single-shot (FOCUS) diffusion-weighted imaging (DWI) in the thyroid gland by comparing its image quality with conventional DWI (C-DWI) qualitatively and quantitatively using a dedicated surface coil exclusively designed for the thyroid gland at 3 T magnetic resonance imaging (MRI). MATERIALS AND METHODS: In this prospective study, 32 healthy volunteers who had undergone 3 T the thyroid gland MRI with FOCUS-DWI and C-DWI were enrolled. Two independent reviewers assessed the overall image quality, artefacts, sharpness, and geometric distortion based on a five-point Likert scale. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) were quantified for both sequences. Interobserver agreement, qualitative scores, and quantitative parameters were compared between two sequences. RESULTS: Agreement between the two readers was good for FOCUS-DWI (κ = 0.714-0.778) and moderate to good for C-DWI (κ = 0.525-0.672) in qualitative image quality assessment. Qualitatively, image quality (overall image quality, artefacts, sharpness, and geometric distortion) was significantly better in FOCUS-DWI than that in the C-DWI (all p<0.05); however, quantitatively, FOCUS-DWI had significantly lower SNRs (p<0.001) and CNRs (p=0.012) compared with C-DWI. The ADC value on FOCUS-DWI was significantly higher than that on C-DWI (p<0.001). CONCLUSION: FOCUS-DWI depicted the thyroid gland with significantly better image quality qualitatively and less ghost artefacts, but had significantly lower SNR and CNR quantitatively, compared with C-DWI, suggesting that both DWI sequences have advantages and could be chosen for different purposes.

[A novel mutation of SPAST gene in a hereditary spastic paraplegia type 4 family].

Objective: To clarify the pathogenicity and further explore the association between genotype and clinical phenotype of this variant, analyzing a novel variation of SPAST gene in hereditary spastic paraplegia (HSP) family from Changzhi city, Shanxi Province. Methods: A family with HSP was tracked and collected in Neurology Department of Heping Hospital Affiliated to Changzhi Medical College in October 2019. Peripheral venous blood of 2 ml was extracted from the proband and 8 other members of the family, genomic DNA was extracted from the blood samples, and the genes of spastic paraplegia were screened by next-generation sequencing (NGS). HGMD, 1000G, OMIM databases and PolyPhen2, SIFT and other software were used for bioinformatics analysis of suspected mutations. Multiplex ligation-dependent probe amplification (MLPA) was used to further screen for total deletions/duplications in patients who remained negative after targeting NGS, and Sanger sequencing was performed to verify the suspected pathogenic mutation sites in the family to determine co-isolation of the mutation sites in the family members. Finally, it is necessary to refer to the latest version of The American College of Medical Genetics and Genomics (ACMG) sequence variation interpretation guidelines to interpret the mutation sites to determine pathogenicity. Results: The HSP family consist 47 members of 4 generations and 10 patients, with onset ages ranging from 2 to 44 years. The proband's daughter only showed positive bilateral Babbitt signs on physical examination, and the rest of the patients showed spasticity and weakness of lower limbs with varying severity on this basis. Preliminary screening by next-generation sequencing technology showed that the proband had frame-shift variation of SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) and missense variation of DCTN1 gene c.2213A>G (p.Gln738Arg). Then, Sanger sequencing was used for in-family verification, which showed SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) was detected in the affected members include father, brother, son and daughter, and not detected in the unaffected normal members, the proband's wife, mother, sister and sister-in-law. However, the unaffected of mother detected missense variation of DCTN1 gene c.2213A>G (p.Gln738Arg), while the remaining members did not detect this variation. The results of MLPA showed that no large fragment variation was found. Conclusions: The genetic pattern of the HSP family was autosomal dominant, and the clinical characteristics were consistent with hereditary spastic paraplegia type 4 (SPG4). Co-segregation of SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) was found in the HSP family and was the pathogenicity cause of this SPG4 family, and it was a newly discovered mutation locus.

[Clinical analysis of 5 cases of dermatomyositis complicated with macrophage activation syndrome].

To investigate the clinical and immunological features of dermatomyositis (DM) complicated with macrophage activation syndrome (MAS). The demographic and clinical characteristics of five patients diagnosed with DM complicated with MAS hospitalized in the Department of Rheumatology and Immunology, Peking University People ' s Hospital from 2011 to 2021 were collected. The results of clinical manifestations, laboratory tests, immunological features, treatments and prognosis were analyzed and summarized. In this study, five female patients in Peking University People's Hospital with an average age of 63.8 (44.0-83.0) years and an average disease duration of 16.1 (1.5-48.0) months. All the patients had typical DM rash (such as heliotrope sign, V/shawl sign or Gottron's sign/papules). They all had muscle involvement (including myalgia or muscle weakness). Two patients had positive myositis-specific antibodies (MSAs), in which case 1 had anti-TIF1-γ antibody and case 5 had anti-NXP-2 antibody. Four patients had interstitial lung disease except case 3. All of the cases developed MAS in the active stage of DM. Common manifestations of MAS in these five patients included high-grade fever, cytopenia, decreased fibrinogen, elevated ferritin and increased soluble CD25. Case 1 presented with neutropenia (0.6×109 /L), thrombocytopenia (26.0×109 /L), hypofibrinogenemia (0.9 g/L), markedly elevated ferritin (26 331.0 µg/L), decreased NK cell activity. Case 2 had anaemia (hemoglobin 81.0 g/L), thrombocytopenia (55.0×109 /L), hypertriglyceridemia (4.7 mmol/L), hypofibrinogenemia (1.2 g/L), elevated ferritin (>100 000.0 µg/L), hemophagocytosis in bone marrow. Case 3 had anaemia (hemoglobin 88 g/L), decreased fibrinogen (1.9 g/L), increased ferritin (>27 759.0 µg/L), splenomegaly, hemophagocytosis in bone marrow. Case 4 suffered from neutropenia(0.3×109 /L), anaemia(hemoglobin 78 g/L), hypertriglyceridemia (4.2 mmol/L), hypofibrinogenemia (0.9 g/L), increased ferritin (>100 000.0 µg/L), and decreased NK cell activity. Case 5 presented anaemia (hemoglobin 60.0 g/L), thrombocytopenia (67.0×109 /L), hypertriglyceridemia (12.7 mmol/L), decreased fibrinogen (1.1 g/L), and elevated ferritin (>923.0 µg/L). All the patients were treated with methylprednisone pulse therapy (200-500 mg) combined with cyclosporine while case 5 received rituximab after methylprednisone pulses. In addition, case 3 also received the combination of mycophenolate mofetil. Case 1 was given etoposide while case 4 was treated with cyclophosphamide and repeated plasmapheresis at the same time. Moreover, intravenous immunoglobulin was added meantime apart from case 3. The condition of four patients improved significantly, nevertheless case 4 experienced recurred pulmonary symptoms and died of respiratory failure. As for complications about infection, case 2 had bacterial infection with high level procalcitonin (PCT) before MAS treatment and condition was improved after empiric antibacterial therapy. Case 3 had cytomegalovirus DNAemia before diagnosis of MAS and viral titer turned negative after ganciclovir therapy. After treatment of MAS, four patients developed cytomegalovirus DNAemia except case 3, in which case 5 was co-infected with bacteria. To sum, DM complicated with MAS is relatively rare, and its patients are of ten in life-threatening condition. Early detection, treatment and prevention of infection during treatment are critical to improve the prognosis.

[Role of preoperative ultrasound-guided inferior parathyroid gland localization and new classification to assist intraoperative search and protection of parathyroid glands].

Objective: To investigate the role and significance of ultrasound-guided inferior parathyroid gland (IPTG) localization in searching and protecting parathyroid glands before thyroid surgery. Methods: A randomized controlled trial study was conducted. A total of 306 patients (433 cases of lateral parathyroidectomy) who underwent primary thyroidectomy and central lymph node dissection in Beijing Tongren Hosipital from March to October 2021 were enrolled. In order to locate IPTG more quickly and effectively, new IPTG classification and the definition of quadrant position were carried out. The patients were divided into the study group (n=228) and the control group (n=205). The study group underwent ultrasound-guided IPTG examination before operation and measured the distance between the IPTG and the lower pole of the thyroid and the midline of the trachea. During the operation, the IPTG was found and protected depending on the localization. The control group did not use any auxiliary preoperative positioning method. The distribution ratio of IPTG and the coincidence rate between intraoperative validation and ultrasound localization were calculated. Results: There were 306 patients enrolled in the final analysis (95 males and 211 females), with a median age of 41 years old (18-70). Type Ⅱ and Ⅲ IPTG accounted for 77.2% (176/228) of the total cases. The total coincidence rate ranged from 72.8% to 79.4% in different IPTG groups. Type Ⅲ and quadrant 2 IPTG had the highest coincidence rate [92.4% (73/79) and 92.9% (79/85), respectively]. The study group had better in situ retention rate [82.0% (187/228) vs 73.2% (150/205), χ2=4.896, P=0.027] and less implantation rate [8.8% (20/228) vs 16.1% (33/205), χ2=5.393, P=0.020] than those of the control group. The in situ retention rate were better in type Ⅲ IPTG group, compared with those of the control group [94.9% (74/78) vs 77.4% (48/62), χ2=7.898, P=0.005]. There was no permanent hypoparathyroidism in two groups and the temporary hypoparathyroidism rate was 32.0% (24/75) and 34.6% (18/52), respectively (χ2=0.095, P=0.758). Conclusion: Ultrasound-guided IPTG localization examination has important implications for searching and protecting IPTG during operation, which can significantly increase in situ retention rate of IPTG and decrease the implantation rate.

[Establishment of morphological reference values for the differential count of white blood cells in peripheral blood smear, as well as nucleated cells and megakaryocytes in bone marrow smear].

Objective: To establish the morphological reference values for the differential count of white blood cells in peripheral blood smear as well as nucleated cells and megakaryocytes in bone marrow smear. Methods: From April 2012 to June 2020, 4 221 healthy donors for hematopoietic stem cell transplantation in Hebei Yanda Lu Daopei Hospital were selected. The median age was 36 (3-72) years old, including 2 520 males and 1 701 females. They were divided into four groups according to age: children group, with age≤14 years old [n=334, 11 (3-14) years old], youth group, with age >14 years old and <45 years old [n=2 855, 33 (15-44) years old], middle-aged adult group, with age ≥45 years old and < 60 years old [n=929, 49 (45-59) years old], and older adult group, with age ≥60 years old [n=103, 62 (60-72) years old]. Gender subgroups were established in each age group. According to different hematopoietic characteristics, the children group were divided into two subgroups: children group 1 [n=48, 6 (3-7) years old] and children group 2 [n=286, 11 (8-14) years old]. According to the clinical routine, 100 white blood cells in peripheral blood, 200 nucleated cells in bone marrow, and cell numbers/4.5 cm2 for megakaryocytes were classified and counted. The results of cell count in different age and gender groups were compared, and the reference values of morphological classification were established for different groups with statistical or clinical significance. Results: Due to the existence of statistically significant differences between children and adult groups and different gender subgroups in adults (all P<0.05), the reference values were established for children group and adult gender subgroups. The counts of segmented neutrophils and lymphocytes in peripheral blood were 46.65(43.97-49.32)% and 44.00(10.60-65.10)% in children group 1, 50.73(49.50-51.96)% and 39.55 (38.36-40.74)% in children group 2, and 57.00 (39.00-75.23) % and 33.00 (17.00-52.00) % in adult group, respectively. Bone marrow segmented neutrophils, orthochromatic erythroblasts, and mature lymphocytes were 11.54 (10.68-12.41)%, 14.20 (13.19-15.21)%, and 23.99 (22.06-25.92)% in children group 1, 12.50 (7.00-21.50)%, 15.00(9.50-25.50)%, and 21.02 (20.24-21.81)% in children group 2, 13.50 (7.50-21.00)%, 16.50 (10.50-26.00)%, and 15.50 (7.50-26.00)% in adult male group, and 14.50 (8.00-24.50)%, 14.50 (9.00-23.00)%, and 17.50 (8.50-29.00)% in adult female group, respectively. The myelopoiesis/erythropoiesis ratio in children group, adult male group and adult female group was 1.86∶1 (1.14∶1-3.23∶1), 1.96∶1 (1.12∶1-3.19∶1), 2.22∶1 (1.30∶1-3.69∶1), respectively. The numbers of granular megakaryocytes and thromocytogenic megakaryocytes were 138 (25-567) cells/4.5cm2 and 86 (13-328) cells/4.5 cm2 in children group, and 92 (13-338) cells/4.5 cm2 and 38 (3-162) cells/4.5 cm2 in adult group, respectively. Conclusion: The morphological reference values for the differential count of white blood cells in peripheral blood smear as well as nucleated cells and megakaryocytes in bone marrow smear are successfully established, which is helpful to improve the application of morphological examination in disease screening, diagnosis and monitoring.

[Importance of full-cycle management for diabetic retinopathy].

Diabetic retinopathy (DR), one of the chronic complications of diabetes, is a serious and irreversible blinding disease. It is difficult to detect in the early stage, to control in the progressive stage, to operate in the advanced stage of DR. Recently, the "14th Five-year plan" for National Eye Health proposed to "improve the management mode of chronic eye disease, and build a chronic disease management system". The project team used artificial intelligence technology based on cloud platform, joint outpatient service, virtual ward to explore the comprehensive management of DR from the aspects of early screening, multidisciplinary collaborative diagnosis and treatment, and refined blood glucose management during perioperative period. In the future, it is urgent to integrate DR chronic disease management with other systemic chronic diseases to reduce the blindness caused by DR.

[Study of three kinds of primary immunization schedules with poliovirus vaccine].

Objective: To compare the immunogenicity of three kinds immunization programs with poliovirus vaccine. Methods: Healthy infants aged 2 months or over were selected and divided into three groups by complete randomization method. Basic immunization with Sabin inactivated poliovirus vaccine(sIPV) and bivalent oral poliovirus vaccine(bOPV) were completed. Three kinds of basic immunization procedures were 1sIPV+2bOPV,2sIPV+1bOPV and 3sIPV, respectively.Two qualified serums that before basic immunization and 28-42 days later were collected, and measured the poliovirus neutralizing antibody with microcell neutralization method. To compare the difference by analysis of variance, rank test and χ2 test. Results: After the basic immunization, 205 subjects of the positive conversion rate of poliovirus neutralizing antibodies of types Ⅰ, Ⅱ and Ⅲwere all higher than 97.00%, and the positive rates were all higher than 98.00%, the geometric mean titer (GMT) of neutralizing antibody was significantly higher than that before basic immunization in three groups.There were significant differences in the positive rate and GMT before and after basic immunization of typeⅠ, Ⅱand Ⅲ in the three (P<0.05). The highest GMT in three groups after basic immunization were all typeⅠ, followed by type Ⅲ, and the lowest in type Ⅱ. The GMT of type Ⅱin 2sIPV+1bOPV and 3sIPV groups were both higher than that in sIPV+2bOPV group. Conclution: After three kinds of basic immunization, the poliovirus neutralizing antibodies of serum were all at high levels in three groups, which could form an effective immune barrier against poliovirus. The immunogenicity of three kinds of basic immunization programs were all well, but there were certain differences of neutralizing antibodies among three kinds basic immunization programs. The immunogenicity in 2sIPV+1bOPV and 3sIPV groups against typeⅡpoliovirus were better than that in 1sIPV+2bOPV group.

[D-dimer contributes to the diagnosis and prognosis in hepatitis B-related acute-on-chronic liver failure].

Objective: To investigate the diagnostic and prognostic value of D-dimer level in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF). Methods: A total of 142 cases diagnosed with ACLF were randomly selected as research objects in the open cohort using the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF). Plasma D-dimer levels were compared between patients with ACLF and non-ACLF and patients with different ACLF grades. Survival and death group D-dimer levels were compared with the end points of 28 days and 90 days, respectively. The correlation between D-dimer and other laboratory indicators and prognostic scores were investigated. Area under receiver operating characteristic curve (AUROC) was used to evaluate the D-dimer value for predicting the prognosis of ACLF patients. 125 external ACLF cases were used for validation. A Student t test or Mann-Whitney U test was used to compare continuous measurement data between two groups. Kruskal-Wallis test was used to compare continuous measurement data between multiple groups. Results: Plasma D-dimer levels in the ACLF [2 588.5 (1 142.8, 5 472.8) µg/L] ] and non-ACLF group [1 385.5 (612.0, 3 840.3) µg/L] had a significant difference (P<0.001). ACLF-3 patients had significantly higher D-dimer levels than ACLF-1/2 patients (ACLF-3 vs. ACLF-1, P<0.001; ACLF-3 vs. ACLF-2, P<0.05). Patients who died at 28/90 days had significantly higher D-dimer levels than those whom survived (P<0.001). There was a significant positive correlation between D-dimer level with prothrombin time (PT), international normalized ratio (INR), high-density lipoprotein C, as well as various prognostic scores (COSSH-ACLFs, CLIF-C ACLFs, CLIF-OFs, MELDs). AUROC of D-dimer in predicting the prognosis of ACLF patients at 28 days and 90 days was 0.751 (95% CI: 0.649-0.852) and 0.787 (95% CI: 0.695-0.878), respectively, which did not differ significantly compared with the predictive ability of other scores (P<0.05), and similar results were confirmed by an external validation group of 125 cases. Conclusion: D-dimer level is significantly higher in patients with ACLF, so it is an independent predictor of prognosis at 28 and 90 days.

[Dynamic changes of locus coeruleus damage in Parkinson's disease-like mice induced by paraquat].

Objective: To observe the dynamic changes of brainstem locus coeruleus (LC) damage in Parkinson' s disease (PD) -like mice by paraquat (PQ) . Methods: In October 2019, 36 male C57BL/6 mice were randomly divided into the exposure group and the control group, with 18 mice in each group. The mice in the exposure group were given intraperitoneal injection of 15 mg/kg PQ, and the mice in the control group were given intraperitoneal injection of 0.9% saline, twice a week for 8 weeks. Neurobehavioral changes (pole climbing test, swimming test, open field test, tail hanging test, high plus maze test and water maze test) were observed at 4 weeks, 6 weeks and 8 weeks, respectively, and the changes of motor ability, emotion and cognitive function were evaluated. The brain tissue of mice were taken and stained with Hematoxylin-Eosin (HE) to observe the pathological changes of LC. Nissl staining was used to detect the changes of neuronal Nissl bodies in LC. Immunohistochemistry (IHC) staining was used to detect the expression of neuron nuclear antigen (NeuN) , dopamine (DA) neurons and norepinephrine (NE) neuron markers tyrosine hydroxylase (TH) , α-synuclein (α-syn) in substantia nigra (SN) and LC. The expression levels of NeuN, TH and α-syn in the midbrain and brainstem were detected by Western blotting. TUNEL staining was used to detect neuronal apoptosis in LC. Results: Compared with the 4th week of PQ exposure group, the time of pole climbing and swimming immobility were gradually increased, the ratio of open arm residence time of high plus maze test and the number of times of the platform and the residence time of platform quadrant in water maze test were gradually decreased (P<0.05) in the exposure group with the progress of exposure time. The results of HE and Nissl staining showed that the neurons in LC gradually arranged loosely, the nucleus were deeply stained, the cytoplasm was pyknosis, and the number of Nissl bodies gradually decreased (P<0.05) in the exposure group with the progress of exposure time. IHC results showed that the number of NeuN and TH positive cells in SN and LC of mice were gradually decreased, and the positive expression of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. Western blotting results showed that the expression levels of NeuN and TH in the midbrain and brainstem were gradually decreased, and the expression level of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. TUNEL staining showed that the apoptosis rates of neurons in LC were gradually increased (P<0.05) in the exposure group with the progress of exposure time. Conclusion: PQ induces progressive damage in the LC area of PD-like mice, which may be caused by the abnormal accumulation of pathological α-syn in the LC area.

Identification and validation of a hub gene prognostic index for hepatocellular carcinoma.

Aims: We aim to provide new insights into the mechanisms of hepatocellular carcinoma (HCC) and identify key genes as biomarkers for the prognosis of HCC. Materials & methods: Differentially expressed genes between HCC tissues and normal tissues were identified via the Gene Expression Omnibus tool. The top ten hub genes screened by the degree of the protein nodes in the protein-protein interaction network also showed significant associations with overall survival in HCC patients. Results: A prognostic model containing a five-gene signature was constructed to predict the prognosis of HCC via multivariate Cox regression analysis. Conclusion: This study identified a novel five-gene signature (CDK1, CCNB1, CCNB2, BUB1 and KIF11) as a significant independent prognostic factor.

Lay abstract Given the poor success of traditional treatments in improving the prognosis of hepatocellular carcinoma (HCC), we need new techniques to improve survival. The new techniques must be checked for accuracy and we must assess whether we can utilize it to achieve individualized treatment. The finding of this study, which examined genetic differences between tumor tissues and normal tissues, is that patients with a high-risk genetic 'signature' have worse results and a shorter survival time than those with a low-risk profile. We first screen hub genes related to the survival status of HCC patients. Then we construct a risk score model to predict the prognosis of HCC and confirm that the model is highly credible. It is reasonable to believe that our risk score model has a high predictive value for the prognosis of HCC.