AIM: To explore the clinical effect of atomization fumigation of self-formulated Zhibai Dihuang Decoction in the treatment of dry eye syndrome after diabetic cataract(DC)surgery with Yin deficiency and dry heat pattern.METHODS: This study is a prospective controlled study. From February 2022 to June 2024, 80 patients(97 eyes)with Yin deficiency and dry heat type DC postoperative dry eye who met the inclusion and exclusion criteria in our hospital were selected. They were randomly divided into an observation group of 40 cases(49 eyes)and a control group of 40 cases(48 eyes)using a random number table method. The control group was treated with sodium hyaluronate eye drops, while the observation group was treated with a combination of atomization fumigation of self-formulated Zhibai Dihuang Decoction on the basis of the control group. The clinical efficacy, subjective symptom scores, visual indicators [tear film break-up time(BUT), Schirmer's test(SIt), corneal fluorescein staining(FL)], tear inflammatory factors [interleukin-1 β(IL-1β), macrophage chemoattractant protein-1(MCP-1), lipid peroxidation(LPO)], and safety between the two groups.RESULTS: The improvement rate of the observation group was 96%, which was higher than that of the control group(79%, P<0.05). After treatment, the 4 subjective symptom scores in both groups were lower than those before treatment, and the subjective symptom scores of ocular dryness, foreign body sensation, burning sensation, and photophobia in the observation group were lower than those in the control group(all P<0.05). After treatment, BUT and SIt in both groups were higher than those before treatment, and FL was lower than that before treatment, with the observation group having higher BUT and SIt and lower FL than the control group(all P<0.05). After treatment, IL-1β, MCP-1, and LPO in both groups were lower than those before treatment, and the observation group had lower levels of IL-1β, MCP-1, and LPO than the control group(all P<0.05). No adverse reactions were observed in either group.CONCLUSION: The atomization and fumigation of self-formulated Zhibai Dihuang Decoction is significantly effective in treating dry eye syndrome after DC surgery with Yin deficiency and dry heat pattern. It can effectively reduce subjective symptom scores, improve visual indicators and tear inflammatory factors, and has a high level of safety.

Abstract: Stem cells, which are a type of primitive cells with multipotent differentiation potential and self-renewal ability, have the potential to regenerate various tissues and organs. Stem cell drug development is a frontier research field in life sciences. Extensive clinical trials involving stem cells have been conducted for different complicated diseases. Some stem cells have been approved as drugs for some indications, indicating their broad industrial prospects. This review introduces the progress of stem cell drugs around the world, especially in China, and discusses the main problems in the industrialization of stem cell drugs, such as their effectiveness, quality control and safety, so as to provide some reference and insight for the development and rapid industrialization of stem cell drugs.

Objective:To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022.Methods:Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed.Results:A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024.Conclusion:The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

Objective:To analyze the genus, drug resistance/virulence and phylogenetic characteristics of Brucella strains isolated from brucellosis surveillance sentinels in Henan Province from 2013 to 2022, and provide baseline data for the surveillance, early warning and outbreak tracing of brucellosis. Methods:Blood samples were collected from patients with Brucella infection for strain isolation, culture and species identification, drug susceptibility test, whole genome sequencing, splicing and assembly, functional/virulence/resistance gene prediction analysis and phylogenetic tree drawing based on single nucleotide polymorphism (SNP). Results:In 36 brucellosis patients, the majority were men (86.11%, 31/36), young adults aged 18-50 (88.89%, 32/36) and farmers/herdsmen (72.22%, 26/36). A total of 36 strains of Brucella melitensis were isolated, and average 1 305 functional proteins of 21 categories were predicted by strain genome; all the strains carried four main virulence factors (pmm, VirB group, BtpA/BtpB, BvrS/BvrR). The drug sensitivity rate was 100.00% to six types of antibiotics including levofloxacin, rifampicin, doxycycline, streptomycin, tetracycline and gentamicin, they showed different resistances to three antibiotics including compound trimethoprim-sulfamethoxazole, ciprofloxacin and ampicillin. The strains carried four types of resistance genes and two clusters of resistance genes, with four combinations of genotypes, the resistance mechanisms included antibiotic degradation/modification enzymes, resistant nodular cell differentiation (RND) efflux pumps, 16S/23S ribosomal rRNA binding site mutations, etc. The number of SNP differed in the genomes of 36 Brucellamelitensis strains ranged from 0 to 454 and phylogenetic tree was divided into three major branches, with relative branch distances between 0.000 0 and 0.498 6 for each strain. Conclusions:Human Brucellamelitensis strains isolated from surveillance sentinels in Henan from 2013 to 2022 carried multiple virulence and antibiotic resistance genes and had different drug resistance phenotypes. Single nucleotide polymorphism analysis and phylogenetic tree analysis showed significant differences in phylogenetic relationships among different strains.

Objective To investigate T cell subtypes and their functions in liver immune microenvironments among patients with alveolar echinococcosis (AE) using single-cell RNA sequencing (scRNA-seq). Methods Four AE patients that were admitted to Qinghai Provincial People’s Hospital in 2023 for hepatic surgery for the first time were enrolled, and liver specimens were sampled 1 cm (peri-lesion, PL group) and > 5 cm from AE lesions (distal lesion, DL group) among each patient. Finally, a total of eight liver specimens were sampled from four AE patients for scRNA-seq analysis. Genome and transcriptome data of liver specimens were processed using the software Cell Ranger and R package. Differentially expressed genes (DEGs) and their biological functions were analyzed using gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the primary intercellular communication patterns and interaction mechanisms were identified among T cell subtypes in liver specimens using the CellChat package. In addition, the developmental stages of T cells were subjected to trajectory analysis with the monocle package to investigate the expression of genes associated with cell growth and tumor transformation, and to predict the developmental trajectories of T cells. Results All four AE patients were female, with a mean age of (25.00 ± 9.06) years, and there were three cases from Jiuzhi County, Golog Tibetan Autonomous Prefecture and one case from Chengduo County, Yushu Tibetan Autonomous Prefecture, Qinghai Province. The viability of single-cell samples from eight liver specimens was 90.41% to 96.33%, and a total of 81 763 cells were analyzed, with 19 cell types annotated. Of these cell types, 13 were immune cells (87.60%), and T cells (33.13%), neutrophils (15.40%), and natural killer cells (11.92%) were the three most common cell types. Re-clustering of 27 752 T cells and proliferative T cells identified 10 distinct T cell subtypes, with CD8⁺ cytotoxic T cells (23.43%), CD8⁺ naive T cells (12.80%), and CD4⁺ effector memory T cells (17.73%) as dominant cell types. The proportions of T helper 2 (Th2) cells (5.19% vs. 3.63%; χ² = 38.35, P < 0.01) and CD4⁺ effector memory T cells (21.59% vs. 13.67%; χ² = 244.70, P < 0.01) were significantly higher in liver specimens in the PL group than in the DL group, and the proportion of CD4⁺ helper T cells was significantly lower in the PL group than in the DL group (7.50% vs. 14.75%; χ² = 330.52, P < 0.01). KEGG pathway analysis revealed that Th2 cells were significantly enriched in cell apoptosis and multiple cancer-associated pathways, and CD4⁺ effector memory T cells were significantly enriched in the regulation of cytokines and chronic inflammation, while CD4⁺ helper T cells were significantly enriched in immune responses regulation. Trajectory analysis of T cells showed that CD4⁺ helper T cells were at an earlier developmental stage relative to Th2 cells and CD4⁺ effector memory T cells, and the expression of inhibitor of DNA binding 3 (ID3), thioredoxin interacting protein (TXNIP), Bcl2-associated athanogene 3 (BAG3) and heat shock protein family B (small) member 1 (HSPB1) genes appeared a tendency towards a decline over time. Conclusions CD4⁺ effector memory T cells and CD8⁺ cytotoxic T cells are primary interacting cells in the liver specimens of AE patients. Reduced expression of Th2 cells and CD4⁺ helper T cells contributes to an inhibitory immune microenvironment, which promotes immune evasion by Echinococcus multilocularis, and Th2 cells are significantly enriched in multiple cancer-associated pathways, which may be linked to the invasive growth of E. multilocularis.

Objective To investigate the relationship between the expression of programmed death ligand 1(PD-L1)and hypoxia inducible factor-1α(HIF-1 α)with the clinical pathological characteristics and prognosis of gastric cancer patients.Methods The cancer tissues of 100 gastric cancer patients who underwent radical gastrectomy at the First Hospital of Handan City from July 2019 to July 2020 were selected as the research subjects,and their adjacent tissues(normal tissues ≥ 5 cm from the cancer tissues)were as the control group.Immunohistochemical detection of PD-L1 and HIF-1 α was performed by SP method.Spearman correlation analysis was used to analyze PD-L1 and HIF-1 α in gastric cancer tissues.Kaplan-Meier method was used to analyze the 3-year survival relationship of gastric cancer patients.The influencing factors of prognosis and death in patients with gastric cancer were analyzed by univariate and multivariate Cox regression.Results Among 100 gastric cancer patients,52 were PD-L1 positive and 48 were negative;67 were HIF-1 α positive and 33 were HIF-1 α negative,the positive expression rates of PD-L1 and HIF-1α in gastric cancer tissues were 52.00％and 67.00％,respectively,which were obviously higher than those in adjacent tissues(11.00％、18.00％),the difference was statistically significant(P＜0.05).Spearman correlation analysis showed that the expression of PD-L1 was positively correlated with that of HIF-1α in gastric cancer tissues(r=0.730,P＜0.001).The expressions of PD-L1 and HIF-1α in patients with gastric cancer were correlated with TNM stage,lymph node metastasis and local invasion(P＜0.05).The 3-year overall survival rate of gastric cancer patients was 48.00％after surgery,and the 3-years survival rate of patients with positive expression of PD-L1 and HIF-1α were 28.85％and 31.34％,which were lower than those of patients with negative expression of PD-L1 and HIF-1α(68.75％and 81.82％)(Log rank x2=25.155,P＜0.001.Log rank x2=24.552,P＜0.001).Moreover,positive expression of PD-L1 and HIF-1α,TNM staging of Ⅲ-Ⅳ,lymph node metastasis,and local infiltration were independent risk factors for prognosis and death in gastric cancer patients(P＜0.05).Conclusion Both PD-L1 and HIF-1α are highly expressed in cancer tissues of gastric cancer patients,and they are positively correlated.They are also associated with clinical pathological features such as TNM staging,lymph node metastasis,and poor prognosis.

Objective:To analyze the reinfection rates in people previously infected with SARS-CoV-2 in Zhengzhou and Yuzhou cities (first infected with Delta/B.1.617.2 variant), and Anyang city (first infected with Omicron/BA.1.1 variant) in January 2022 and the population characteristics, and compare the differences in antibody levels among different populations.Methods:Serum samples were collected from 371 previously infected, 134 reinfected and 19 uninfected people for IgG antibody detection. Among them, serum samples from 45 previously infected, 44 reinfected and 19 uninfected people were tested with different novel coronavirus variants (early original strain, BA.5.2 variant, XBB.1.5 variant) for neutralizing antibody detection.Results:The rate of reinfection was 32.82% (85/259) in Zhengzhou and Yuzhou cities, and 19.92% (49/246) in Anyang city. The IgG antibody level in reinfected people was higher than that in previously infected and uninfected people ( P<0.05). The IgG antibody level in uninfected group was higher in people vaccinated within three months than in those vaccinated six months ago ( P<0.05). The IgG antibody level in the group receiving four doses of vaccine was higher than that in the group receiving three doses of vaccine ( P<0.05). The results of true virus neutralization antibody detection showed that in the Zhengzhou and Yuzhou cases, the level of neutralization antibody against the early original strain was higher than those against the BA.5.2 variant and the XBB.1.5 variant ( P<0.05), and the level of neutralizing antibody against BA.5.2 variant was higher than that against XBB.1.5 variant ( P<0.05). In Anyang city cases, the level of neutralizing antibody against the early original strain was higher than those against BA.5.2 variant and XBB.1.5 variant ( P<0.05); in the reinfected population, the level of neutralizing antibody against the early original strain was higher than that against the XBB.1.5 variant ( P<0.05). In addition, the levels of all neutralizing antibodies in both previously infected and reinfected people were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody in the infected population in Zhengzhou and Yuzhou cities was higher than that in the infected population in Anyang city and in uninfected population ( P<0.05). The levels of antibodies against BA.5.2 and anti-XBB.1.5 variants in infected people in Zhengzhou and Yuzhou cities were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody against BA.5.2 variants in the previously infected population in Anyang city was higher than that in the uninfected population ( P<0.05), and the level of neutralizing antibody against XBB.1.5 variants in the infected population in Anyang city was higher than that in the uninfected population ( P<0.05). Conclusions:After infection with SARS-CoV-2, the neutralizing antibodies produced in the human body have a certain cross-protection effect on other variants, but the antibody level will gradually decrease over time. Protection from a previous early SARS-CoV-2 variants infection against the current main circulating Omicron variants (such as XBB variants) is low, and the immunity conferred by pervious infection or booster vaccination may not be able to provide sufficient protection against new variants.

Objective:To analyze the whole genome of Omicron variants causing the first local Omicron outbreak in Henan Province and to investigate the mutations in the SARS-CoV-2 genome for source tracing.Methods:Respiratory tract samples from COVID-19 cases in the Omicron outbreak in Henan Province from January 7 to 29, 2022 were subjected to whole-genome sequencing and sequence alignment analysis. Whole-genome identity, variations and evolution of the Omicron variants were analyzed.Results:Through high-throughput sequencing, the whole-genome sequences of SARS-CoV-2 were obtained from 120 cases, which accounted for 25.64% (120/468) of all COVID-19 cases in Anyang during the same period. Compared with the genome of Wuhan reference strain (NC_045512.2), there were 57-59 nucleotide mutation sites in the 120 whole genome sequences, and one or two nucleotide mutation sites were added to the shared 57 nucleotide sites. All of the 120 strains were VOC/Omicron (BA.1.1) variants and shared high homology. The whole-genome sequence obtained from the first case A contained 57 nucleotide mutation sites, while apart from the 57 identical nucleotide mutation sites, one specific mutation site (C1594T) was found in the whole-genome sequence obtained from the first case B, suggesting that the two cases were in the same transmission chain. After comparing with the database of domestic and imported cases by the Chinese Center for Disease Control and Prevention and the Henan Provincial Center for Disease Control and Prevention, it was found that the current outbreak was linked with the same transmission chain as the existing local epidemics in other provinces. Moreover, epidemiological investigation showed that on January 2, case A had come into contact with her cousin and his family who returned from an affected area outside the province.Conclusions:Based on the gene sequencing results and epidemiological investigation, the COVID-19 outbreak in Anyang city, Henan Province was a local epidemic and the source of it was a college student who returned to Anyang city from other province on December 28, 2021. These infections were linked to the same transmission chain as the existing local infection in other provinces.

Objective:To report the first case of sever fever with thrombocytopenia syndrome caused by severe fever with thrombocytopenia syndrome virus (SFTSV) in Puyang city, and to study the epidemiological and molecular characteristics of S, M, L fragments of the SFTSV isolate.Methods:The epidemiological characteristics of this case was analyzed with epidemiological methods. SFTSV was isolated from the patient′s serum sample. Nucleic acid of SFTSV was extracted and detected by fluorescent RT-PCR. A multiplex PCR method was constructed to amplify the nucleic acid sequence of the virus. whole-genome sequencing was performed on the next-generation sequencing platform. MEGA11 and DNAStar was used for homology analysis and a phylogenetic tree was constructed.Results:Epidemiological investigation showed that the patient and his close contacts had no history of travel or tick bite within 14 d, but had a history of fieldwork. The patient′s serum sample was positive for SFTSV nucleic acid. Genetic analysis showed that the S, M, L gene fragments of the first SFTSV isolate in Puyang belonged to genotype E. This isolate shared 94.8%-99.6%, 94.0%-99.8% and 95.7%-99.7% nucleotide sequence homology with the representative strains acquired from GeneBank in S, M, L gene fragments, respectively.Conclusions:This case was the first case of SFTSV-caused severe fever with thrombocytopenia syndrome in Puyang. The SFTSV isolate shared a close homology with domestic isolates, but its genotype was significantly different from the SFTSV strains isolated in Henan in recent years, indicating that it might an imported case from other places in Henan Province or Hubei Province. Disease monitoring and professional training for medical personnel should be strengthened and more attention should be paid to the evolution and mutation of SFTSV.

ObjectiveTo explore the effect of Weiwei Tongtiao decoction （WTD） on chronic atrophic gastritis （CAG） rats and the underlying mechanism. MethodA total of 90 SD rats were randomized into normal control group， model group， high-dose， medium-dose， and low-dose WTD groups （18， 9， 4.5 g·kg^-1·d^-1 WTD， respectively， ig）， and weifuchun control group （0.45 g·kg^-1·d^-1 weifuchun aqueous solution， ig）， with 15 rats in each group. The N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） was employed to induced CAG in rats. After the modeling （identified by histopathological examination）， the administration began and lasted 12 weeks. Then， gastric mucosa tissues of the rats were collected and stained with hematoxylin and eosin （HE）， and the pathological changes of gastric mucosa were observed under the optical microscope. Real-time PCR， immunohistochemistry （IHC）， and Western blotting were applied to examine the mRNA and protein expression of indexes in nuclear factor kappa-B （NF-κB） signaling pathway in the gastric mucosa of rats. ResultCAG rats showed irregular arrangement and morphology of the inherent glands in gastric mucosa and the glands decreased or disappeared. In addition， inflammatory cell infiltration was observed in the lamina propria of CAG rats， and about 48.4% presented intestinal metaplasia. WTD significantly alleviated the reduction of the glands and intestinal metaplasia in a dose-dependent manner. Compared with the normal control group， the model group demonstrated increase in the mRNA expression of cyclooxygenase-2 （COX-2）， NF-κB p65， interleukin （IL）-1α， IL-1β， IL-10， IL-8α， and IL-8β， and protein expression of COX-2， NF-κB p65， and IL-10 （P<0.01）. WTD and weifuchun lowered the mRNA expression of COX-2， NF-κB p65， IL-1α， IL-1β， IL-10， IL-8α， and IL-8β， and the protein expression of COX-2， NF-κB p65， and IL-10 in gastric mucosa of CAG rats （P<0.01）. The expression of the above indexes after the intervention with high-dose WTD was close to that of the normal control group. ConclusionWTD can improve or even reverse the diseased gastric mucosa of CAG rats， and the mechanism is the likelihood that WTD down-regulates the mRNA and protein expression of the indexes in NF-κB signaling pathway in gastric mucosa of CAG rats.