Abstract: Objective To analysis the genetic evolution characteristics of hemagglutinin (HA) gene of influenza A(H1N1)pdm virus in Changsha City from 2016-2023, to understand the trend of the HA genetic evolution and the mutations of the amino acid. It provides a scientific basis for the prevention and control of influenza epidemics, as well as the screening of vaccines under the new situation. Methods The A(H1N1)pdm09 virus strains from Changsha City from 2016 to 2023 were isolated using SPF chicken embryos, and then the HA genes were sequenced by MiSeq of Illumina Inc. The homology of HA gene was analyzed by MegAlign of the DNASTAR, and the phylogenetic tree was constructed using the Neighbor Joining (NJ) method in the Molecular Evolutionary Genetics Analysis version 11 (MEGA11). Results The homology of the HA gene of A(H1N1)pdm virus in Changsha from 2016 to 2023 was between 94.8%-99.9%, with the HA gene homology decreasing annually. The homology between the isolated strains of A(H1N1)pdm09 in Changsha City from 2016 to 2023 and the WHO recommended vaccine strain ranged from 96.8% to 99.0%, indicating a relatively good match between the flu isolates and the recommended vaccine strain. The phylogenetic tree of the HA gene of the A(H1N1)pdm09 influenza virus in Changsha City showed that the HA gene evolved into several different branches within the 6B branch, and it had currently evolved to 6B.1A.5a.2a branch. Constant mutations had occurred at the amino acid sites of the four antigenic determinant clusters of HA protein. Currently, amino acid mutations had occurred at 15 antigenic sites within the four antigenic determinant clusters, and the newly emerged A186T antigen mutant site in the isolates from 2023 was worth recent notice. The receptor-binding sites are relatively conserved in loop 130, minor amino acid mutations occurred in loop 220, whether the amino acid mutation site in loop 190 is becoming more stable needs to be further monitored. Taking A/California/07/2009 (CY121680) as the reference strain, most of the A(H1N1) pdm09 isolates in Changsha was increased 162 NQTY glycosylation site and was decreased 276 NTTC glycosylation site, and the glycosylation mutations at these two sites have become more stable recently. Conclusions The HA genes of influenza A(H1N1)pdm virus in Changsha are constantly evolving and mutating, suggesting influenza surveillance should be strengthened continuously.

Objective:To investigate characteristics of the 18F-flurodeoxyglucose ( 18F-FDG) uptake intensity and ranges in distinct hepatic alveolar echinococcosis lesions. Methods:The clinical data of 39 patients with position emission tomography during Jan 2017 to Dec 2019 in the First Affiliated Hospital of Xinjiang Medical University were enrolled. Among them, there were 17 males and 22 females, aging from 15 to 65 years (median 34 years). Lesions were classified into six groups based on heterogenic scales of calcification and liquefaction: A. non-calcified and non-liquefied ( n=7); B. obvious calcified and non-liquefied ( n=7); C. partial calcified and partial liquefied( n=10); D. obvious calcified and partial liquefied ( n=5); E. partial calcified and subtotal liquefied ( n=5); F. obvious calcified and subtotal liquefied ( n=5). Tumor to background ratio (TBR) and width (W) of lesion infiltrative boundary were measured and calculated. Statistical comparison using Mann-Whitney U test as well as correlation analysis was performed. Results:TBR values [ M( Q1, Q3)] for each group were 4.40(3.66, 7.03), 2.55(1.69, 3.60), 3.73(3.37, 5.21), 2.90(2.75, 3.60), 3.80(3.49, 6.36), 2.49(2.21, 3.97), among which A>B, A>D, A>F, C>B, E>B ( U=3.0, 4.0, 4.5, 11.0, 5.0, all P<0.05); From the perspective of the calcification in each group, it was found that the lighter the calcification was, the greater the TBR value was. W values [ M( Q1, Q3)] for each group were [12.5(10.0, 19.5), 11.2(10.5, 12.5), 12.2(10.9, 13.2), 7.8(7.3, 9.3), 10.0(7.3, 13.4), 7.3(6.8, 7.6)] mm, among which A>D, A>F, B>D, B>F, C>D, C>F (all U=0, all P<0.05); According to the degree of calcification and liquefaction of lesions in each group, the lighter the calcification was, the greater the W value was; The heavier the liquefaction was, the smaller the W value was. A mild strength linear correlation has been observed between the TBR value and W value ( r=0.4136, P<0.05). Conclusions:Less calcification and liquefaction implicated higher 18F-FDG uptake intensity and wider range. Radical resection margins and tissue sampling should be individualized based on different lesion features in surgical treatment.

In the context of the national strategy of promoting the research and development of food and drug homologous substances, it is necessary to study the regulatory model of food and drug homologous substances as food. Medicinal and food homologous substances are regulated as "Chinese medicinal materials" or "Chinese decoction pieces" in the drug category, and as "food and drug homologous substances", "agricultural products" or "traditional Chinese medicine healthy food" in the food category. Drug supervision focuses on quality, while food supervision focuses on safety, and it is worth exploring whether there is a blind spot in the supervision of food and drug substances completely based on the food concept. In this paper, Lonicerae Japonicae Flos, as drug and food homologous substance, is selected as the research object, and its quality regulation status is investigated by reviewing the relevant laws and regulations and standards on food, analyzing the quality information and test results of the samples, and analyzing the necessity of quality regulation when serving as food, in order to provide a basis and reference for the way food substances are regulated.

Strengthening the standard formulation and quality management of traditional Chinese medicine（TCM） dispensing granules is an important part of the strategic planning for the development of TCM in China. In order to examine the clinical application and overall quality control of the existing national standards for TCM dispensing granules， this study classified and summarized the varieties in the existing standards， analyzed their clinical applicability， and discussed the characteristics of the test methods for identification， content determination and specific chromatogram/fingerprint. It was found that the coverage of the existing standards was inadequate in terms of quantity， and it was even weaker in the aspects of therapeutic efficacy， herb family， processing method and preparation method of TCM dispensing granules. It was concluded that the characteristics of national standards in test methods were summarized as follows：guided by clinical application， based on the reference system， taking specific chromatogram as a breakthrough， so as to improve the overall quality control of TCM dispensing granules. It is suggested that the coverage of national standards should be subsequently expanded to meet the needs of market development. In order to enhance clinical applicability， the content of national quality standards should be increased， including increasing variety diversity to meet the needs of clinical application， raising the standard requirements to improve the clinical medication experience， and strengthening effectiveness research to highlight clinical efficacy. At the same time， the accessibility of regulatory inspection is enhanced， the rules for the management of varieties without national standards are promulgated to lay the foundation for the healthy and orderly development of TCM dispening granule industry.

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Objective:To investigate the safety and feasibility of hepatectomy in the treatment of hepatic alveolar echinococcosis with secondary cavernous transformation of the portal vein.Methods:The clinical data of 7 patients undergoing surgery at the First Affiliated Hospital of Xinjiang Medical University from Jan 2010 to Dec 2019 were retrospectively analyzed.Results:There were 1 case of cavernous type Ⅰ transformation of the portal vein and 6 cases of type Ⅱ. All patients underwent partial hepatectomy. The average operation time was (9.24±4.09) h. Two patients underwent resection of cavernous segment of portal vein and reconstruction by graft, Albendazole was taken orally for 2 years after discharge. Anticoagulants were taken orally in patients with artificial vascular reconstruction. No recurrence and vascular complications were found. Five patients underwent palliative resection without resection of the cavernous segment of the portal vein. During the follow-up, cavernous transformation of the portal vein progressed in 3 patients, 2 of them esophageal varices rupture and bleeding.Conclusion:Radical hepatectomy and revascularization are the first choice for the treatment of hepatic alveolar echinococcosis complicated with secondary cavernous transformation of portal vein the result was fair.

Adult ; Echinococcosis/surgery* ; Echinococcosis, Hepatic/surgery* ; Feasibility Studies ; Female ; Hepatectomy ; Humans ; Kidney Diseases/surgery* ; Liver Diseases/surgery* ; Male ; Middle Aged ; Nephrectomy ; Pneumonectomy ; Retrospective Studies ; Treatment Outcome

Objective:To explore the application of different reconstruction methods of retrohepatic inferior vena cava (RHIVC) in the ex-vivo liver resection and auto-transplantation(ELRA)for hepatic alveolar echinococcosis (AE).Methods:The 88 patients with end-stage hepatic AE treated by ELRA from August 2010 to December 2018 were divided into 3 groups according to the different methods of RHIVC reconstruction, respectively , group A, autologous vascular repair and reconstruction group (n=50); group B, RHIVC replacement group (n=31); group C, RHIVC resection without reconstruction group (n=7), and the clinical data were analyzed and followed up.Results:The average operation time of group A, B and C was 16.32±3.20 h, 15.99±3.32 h, 16.86±4.18 h ( P>0.05), The average anhepatic phase was398.48±104.12 min, 389.41±135.25 min, 337.43±108.65 min( P>0.05), The differences were not statistically significant. The average hospital stays after surgery in the three groups were 30.64±18.54 d, 25.94±16.37 d, 51.29±29.43 d ( P<0.05), There were significant statistical differences, and the results showed that the group B was significantly less than other two groups. The incidence of IVC related complications in group A and B was 20.0% and 9.7%. Among all the subjects, RHIVC stenosis was found in 9 patients and thrombus was formed in 4 patients in postoperative. Conclusions:RHIVC reconstruction methods can be selected appropriately according to the defect degree of lumen after resection.

Objective: To evaluate the residual radioactivity after ¹³¹I treatment in postoperative inpatients with differentiated thyroid carcinoma (DTC) using service robot in nuclear medicine ward, and assess the time for patients to be released from isolation. Methods: From September 2017 to June 2018, 297 patients (94 males, 203 females, age: 19-80 years) with DTC who underwent ¹³¹I treatment after surgery were included. According to the purpose of treatment and the prescription dosage of ¹³¹I, patients were divided into 8 groups: 4 groups accepted ¹³¹I remnant ablation therapy (RAT) with different dosages, which were 3 700 MBq (RAT1, n=34), 4 440 MBq (RAT2, n=122), 5 550 MBq (RAT3, n=81) and 7 400 MBq (RAT4, n=27), respectively; 4 groups had ¹³¹I treatment for recurrent/metastatic lesions (RMLT), and the dosages were 3 700 MBq (n=1), 4 440 MBq (n=2), 5 550 MBq (n=14) and 7 400 MBq (n=16). At 4, 24, 48 and 72 h after ¹³¹I administration, the dose equivalent rates at 2 cm away from the patient′s neck and at 1 m away from the body were measured by the robot designed for nuclear medicine ward. Kruskal-Wallis rank sum test and Mann-Whitney U test were used to analyze the data. Results: Neck dose equivalent rates for patients with RAT at different time points (4, 24, 48 and 72 h) after ¹³¹I administration were significantly different among 4 groups (H values: 20.889-46.410, all P<0.05), as well as the body dose equivalent rates (H values: 27.181-35.497, all P<0.05). The neck dose equivalent rates at 24, 48 and 72 h after ¹³¹I administration were statistically different between group 3 and 4 for patients with RMLT (z values: 2.328-3.076, all P<0.05; data in group 1 and 2 were too limited to be compared), while there was no statistical difference for the body dose equivalent rates (z values: 0.333-1.621, all P>0.05). The radioactivity retention in patients decreased rapidly within 24 h, then slowed down gradually and became extremely low at 72 h. At 72 h after ¹³¹I administration, 96.6%(255/264) patients with RAT and 100%(33/33) patients with RMLT were lower than 23.3 μSv/h, which meant the patients could be discharged from hospitalization. Conclusions Nuclear medicine ward service robots may dynamically measure residual radioactivity in DTC patients who take ¹³¹I treatment, providing individualized isolation solutions.

Objective: To analyze the changes of local immune cells in liver of mice caused by nanosecond pulse therapy for hepatocellular carcinoma. Methods: Forty C57BL-6J of mice were randomly divided into four groups: negative control group (n=10), tumor group (n=10), surgical resection group (n=10) and nanosecond pulse group (n=10). Hepa 1-6 cells were injected into the left hepatic lobe of mice in tumor group, resection group and nanosecond pulse group to construct the orthotopic xenograft tumor model. Left hepatic lobectomy was performed in the surgical excision group and nanosecond pulse was performed in the nanosecond pulse group 7 days after the construction. All mice were sacrificed 7 days after the treatment. CD₃^＋ was detected by flow cytometry in the left hepatic lobe lesion, the nanosecond pulse group and the normal liver tissue of the right hepatic lobe in the liver and tumor groups of the blank control group. T, CD₄^＋T, CD₈^＋T, regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), natural killer cells (NK), B cells, and the ratio of CD₄^＋T to CD₈^＋T. Results: In the blank control group, the tumor group the number of lesion in the mice and the pulse area of the nanosecond pulse group CD₄^＋T cells in blank control group (normal liver)>nanosecond pulse group>tumor group [(25.77±3.76)% vs. (15.72±2.70)% vs. (12.68±3.13)%, P<0.05]; CD₈^＋T cell tumor group>blank control group>nanosecond pulse group [(14.01±2.75)% vs. (13.99±1.41)% vs. (8.42±2.21)%, P<0.05]. The ratio of CD₄^＋T to CD₈^＋T in nanosecond pulse group > blank control group > tumor group [(1.90±0.17) vs. (1.86±0.32) vs. (0.93±0.21), P<0.05]; B cell nanosecond pulse group> blank control group > tumor group [(47.65±3.77)% vs. (33.74±3.91)% vs. (15.94±6.10)%, P<0.05]; MDSC cell tumor group > nanosecond pulse group > blank control group [(18.49±2.74)% vs. (8.41±3.05)% vs. (2.15±0.69)%, P<0.05]. However, CD₃^＋T cells, NK cells and Treg cells showed no statistical significance among the three groups (all P>0.05). Normal liver tissue in right lobe of liver in 4 groups the ratio of CD₄^＋T to CD₈^＋T in blank control group >nanosecond pulse group >surgical resection group >tumor group [(1.86±0.32) vs. (1.85±0.43) vs. (1.52±0.16) vs. (1.36±0.29), P<0.05]; B cell nanosecond pulse group >surgical resection group >blank control group> Tumor group [(46.85±8.30)% vs. (34.23±6.17)% vs. (33.74±3.91)% vs. (27.64±2.20)%, P<0.05]; Treg cell tumor group >resection group>nanosecond pulse group>blank control group [(26.34±6.23)% vs. (7.01±2.04)% vs. (3.63±1.59)% vs. (3.19±1.50)% , P<0.05]; MDSC in tumor group >resection group>nanosecond pulse group>blank control group [(12.22±2.02)% vs. (5.00±0.73)% vs. (2.87±0.96)% vs. (2.15±0.69)%, P<0.05]. However, there were no statistically significant differences in CD₃^＋T, CD₄^＋T, CD₈^＋T and NK cells among the four groups (all P>0.05). Conclusion Nanosecond pulse ablation of primary hepatocellular carcinoma of mice can induce immune response in ablation area and other hepatic lobes, which may be due to the anti-tumor immunity induced by nanosecond pulse.