This paper summarized Professor PI Chiheng's experience in treating diabetic nephropathy （DN） using the method of warming yang， nourishing yin， and invigorating blood by stages. It is believed that yang deficiency and yin depletion are the key pathological mechanisms of DN， with blood stasis running throughout the disease's progression. The general treatment principle is to warm yang， nourish yin， and invigorate blood， with different emphases at each stage. For early stage， the disease is characterized by spleen qi deficiency and insufficiency of qi and yin， which could be treated by modified Shenqi Dihuang Decoction （参芪地黄汤） to tonify qi and invigorate blood， strengthen yang and consolidate yin； for middle stage， the disease is marked by spleen and kidney yang deficiency with internal dampness accumulation， which could be treated by modified Zhenwu Decoction （真武汤） and Sanren Decoction （三仁汤） warming yang and to resolve dampness and unblock meridians； for the late stage， the disease is characterized by blood stasis and toxin accumulation with deficiency of both yin and yang， which could be treated by modified Jisheng Shenqi Pill （济生肾气丸） to eliminate pathological masses and remove toxins， warm yang and nourish yin. Additionally， traditional Chinese medicine therapies such as rubbing with ointment （Gao Mo therapy） are utilized as adjunct treatments， treating the root and branch simultaneously and combining internal and external approaches.

Objective To explore the research hotspots and development trends in the field of cancer treatment in the past decade. Methods The CNKI and Web of Science Core Collection databases were searched for Chinese and English articles related to cancer treatment published over the last 10 years. Bibliometric research methods were employed, including keyword cluster analysis of published literature. Results A total of 45 455 Chinese articles and 866 958 English articles were retrieved. Combining the visualization analysis results and the current research dilemma of tumor treatment revealed that the current research hotspots of tumor treatment domestically and internationally can primarily focus on four key areas. In the realm of targeted therapy, efforts are directed towards the discovery of new drug targets, overcoming resistance to targeted therapy, and the development of monoclonal antibodies and antibody–drug conjugates. In the field of immunotherapy, the emphasis lies in enhancing the response rate to immune checkpoint inhibitors, determining the mechanisms behind resistance to immunotherapy, and improving the safety of treatment. The research in traditional Chinese medicine (TCM) covers evidence-based evaluation studies on TCM treatment, the identification of populations that can gain the most benefit from TCM, and strategies for improving the quality of life. In the area of novel drug development, cutting-edge technologies, such as organoid-based screening for anticancer drugs, synthetic biology, and artificial intelligence, are under investigation. Conclusion New targeted drugs, immune efficacy improvement, multidisciplinary integration, nano-delivery, and TCM innovation are the key research directions in the field of tumor therapy in the future.

To investigate the effect of baicalin (BAI)-loaded cross-linked lipoic acid nanocapsules (BAI@cLANCs) against hydrogen peroxide (H2O2)-induced senescence in human umbilical vein endothelial cells (HUVECs), this study examined the toxicity of BAI@cLANCs on HUVECs by MTT method. The cell nuclear staining, SA-β-gal staining, and MTT methods were used to assess the optimal concentration of H2O2-induced senescence in HUVECs. The cellular uptake of BAI@cLANCs was evaluated using fluorescence microscopy imaging and flow cytometry. The proportion of cellular senescence was determined by SA-β-gal staining. The level of reactive oxygen species (ROS) in senescent cells was detected by fluorescence microscopy imaging and multifunctional microplate reader. The content of malondialdehyde (MDA) in cells was detected by lipid oxidation detection kit, and the cell cycle was analyzed by flow cytometry with propidium iodide staining. The results showed that BAI@cLANCs had no significant effect on the growth of HUVECs in the range of BAI at 2.80−112 mmol/L. 200 μmol/L and 25 minutes were the ideal conditions for H2O2-induced senescence of HUVECs. cLANCs as drug delivery carriers significantly enhanced the uptake efficiency of BAI in HUVECs. Compared with the normal group, the H2O2 model group showed decreased cell viability, increased positive SA-β-gal staining rate, increased ROS and MDA content, as well as increased percentage of cells blocked in S phase and decreased cells entering G2/M phase. Compared with the H2O2 model group, BAI, cLANCs, BAI + cLANCs, and BAI@cLANCs groups showed increased cell viability, decreased positive SA-β-gal staining rate, decreased ROS and MDA content, decreased percentage of S-phase cells, and increased cells entering G2/M phase, with the best anti-aging effect in the BAI@cLANCs group. In summary, the results above showed that both BAI and cLANCs have anti-aging properties. With cLANCs as drug carriers, the anti-aging benefits of BAI@cLANCs are synergistic and can effectively delay H2O2-induced senescence of HUVECs.

Objective To explore the clinical value of noninvasive left ventricular pressure-strain loop(LV-PSL)technique in evaluating myocardial work and left ventricular remodeling before and after percutaneous coronary intervention(PCI)in patients with acute myocardial infarction(AMI).Methods Seventy patients with AMI admitted to our hospital(coronary heart disease group)and 50 healthy adults(control group)who underwent physical examination during the same period were selected,The conventional echocardiographic indexes,left ven-tricular global longitudinal strain(GLS)and left ventricular myocardial work indexes,[global work index(GWI),global work efficiency(GWE),global constructive work(GCW),global wasted work(GWW)]were examined before and 7 days after operation in control group and coronary heart disease group.The differences of the above indexes between the coronary heart disease group and control groups were compared.According to the results of coronary angiography,AMI patients were further divided into a coronary heart disease single-branch group(34 cases)and a coronary heart disease multi-branch group(36 cases),and the differences of the above indexes between the two groups were compared.Analyze the correlation between left ventricular myocardial work indexes and GLS,conventional echocardiographic indexes.Result Left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume(LVEDV)and GWW were higher incoronary heart disease group than in control group before and 7 days after surgery,while left ventricular ejection fraction(LVEF),GWI,GWE,GCW and GLS were lower than control group,with statistical significance(all P<0.05).At 7 days after surgery,LVESV,LVEDV and GWW in the coronary heart disease group were lower than those before surgery,while LVEF,GWI,GWE,GCW and GLS were higher than those before surgery,with statistical significance(all P<0.05).LVESV,LVEDV and GWW at 7 days before and after surgery in the coronary heart disease multi-branch group were higher than those in the coronary heart disease single-branch group,while LVEF,GWI,GWE,GCW and GLS were lower than those in the coronary heart disease single-branch group,with statistical significance(all P<0.05).Correlation analysis showed that GWW was negatively correlated with GLS and LVEF,while GWE,GCW and GWI were positively correlated with GLS and LVEF(all P<0.001).Conclusion LV-PSL technique has good application value in evaluating left ventricular function and left ventricular remodeling in AMI patients before and after PCI,and provides a new non-invasive method for clinical practice.

ATP is an important cofactor involved in many biocatalytic reactions that require energy input. Polyphosphate kinases (PPK) can provide energy for ATP-consuming reactions due to their cheap and readily available substrate polyphosphate. We selected ChPPK from Cytophaga hutchinsonii for substrate profiling and tolerance analysis. By molecular docking and site-directed mutagenesis, we rationally engineered the dual-substrate channel cavity of polyphosphate kinase to improve the catalytic activity of PPK. Compared with the wild type, the relative enzyme activity of the screened mutant ChPPK_K81H-K103V increased by 326.7%. Meanwhile, the double mutation expanded the substrate utilization range and tolerance of ChPPK, and improved its heat and alkali resistance. Subsequently, we coupled the glutathione bifunctional enzyme GshAB and ChPPK_K81H-K103V based on this ATP regeneration system, and glutathione was produced by cell-free catalysis upon disruption of cells. This system produced (25.4±1.9) mmol/L glutathione in 6 h upon addition of 5 mmol/L ATP. Compared with the system before mutation, glutathione production was increased by 41.9%. After optimizing the buffer, bacterial mass and feeding time of this system, (45.2±1.8) mmol/L glutathione was produced in 6 h and the conversion rate of the substrate l-cysteine was 90.4%. Increasing the ability of ChPPK enzyme to produce ATP can effectively enhance the conversion rate of substrate and reduce the catalytic cost, achieving high yield, high conversion rate and high economic value for glutathione production by cell-free catalysis. This study provides a green and efficient ATP regeneration system that may further power the ATP-consuming biocatalytic reaction platform.
Molecular Docking Simulation ; Catalysis ; Glutathione ; Adenosine Triphosphate

Objective:To observe any effect of exosomes derived from umbilical cord mesenchymal stem cells on pain, cartilage repair and the expression of transcriptional activator 3 (ATF-3) and growth related protein 43 (GAP-43) in the dorsal root ganglia (DRG), as well as to explore the mechanism of their relieving pain.Methods:Fifty-four male Sprague-Dawley rats were randomly divided into a sham-operation group, a monoiodoacetate group and an exosome group, each of 18. The knee cavities of the left hind limbs of all of the rats except those in the sham-operation group were injected with 50μl of monoiodoacetate to establish an arthritis pain model. The sham-operation group received only 50μl of saline solution as controls. Two weeks after the modelling, the knee joint cavities of the exosome group were injected with 50μl of exosomes, while the other two groups were injected with 50μl of normal saline. The rats′ mechanical and thermal pain thresholds were measured 1 day before the modeling, 7 and 14 days after the monoiodoacetate injection, as well as 7, 14 and 28 days after the exosome injection. Western blotting was used to detect the expression of ATF-3 and GAP-43 in the rats′ DRG, while hematoxylin and eosin staining was used to detect any cartilage repair.Results:Compared with the monoiodoacetate group, the latency of the mechanical and thermal pain thresholds had increased significantly in the exosome group 7 days after the exosome injection. The difference remained significant until the 28th day after the injection. The expression of ATF-3 protein decreased significantly and that of the GAP-43 protein increased significantly. Significant differences were observed in the average Osteoarthritis Research Society International (OARSI) knee cartilage score.Conclusions:Exosomes can alleviate the pain induced by monoiodoacetate adjuvant. The analgesic mechanism may be related to reducing nerve injury and promoting nerve and cartilage repair, with the nerve repair earlier than cartilage repair.

O BJECTIVE To optimize stir-frying with saltwater technology of Citrus reticulata . METHODS Taking the contents of limonin ，nomilin and obacunone ，color difference value and free radical scavenging rate of 1，1-diphenyl-2-trinitrophenyl hydrazine （DPPH） as the indexes ，the entropy weight method was used for comprehensive evaluation. The stir-frying with saltwater technology of C. reticulata was optimized by central composite design-response surface method by using water-salt ratio ，stewing time，frying temperature and frying time as factors. RESULTS The optimal stir-frying with saltwater technology of C. reticulata included water-salt ratio of 8 ∶ 1（mL/g），stewing time of 22 min，frying time of 9 min and frying temperature of 158 ℃. After three times of validation tests ，the average comprehensive score of the optimized technology was 92.35（RSD＝2.19％），and its relative error with the predicted value （93.25）was 1.10％. CONCLUSIONS The optimal stir-frying with saltwater technology is stable and feasible.

Objective:To identify 3 the disease-causing genes and mutations of Leber congenital amaurosis (LCA), and to study the correlation of phenotype and genotype.Methods:A retrospective study. Four LCA patients and seven family members who were diagnosed by eye examination in Ning Xia Eye Hospital of People's Hospital of Ningxia Hui Autonomous Region from January to December 2021 were included in the study. Four patients were from 3 unrelated families. Detailed collection of medical history and family history were received. Related ophthalmologic examination were collected and genomic DNA was extracted from peripheral blood. Whole-exome sequencing method was used for genetic diagnosis. The identified variant was confirmed with Sanger sequencing. Potential pathogenic mutation was analyzed using software and conserved domain analysis and performed co-separated analysis between the family member and the proband.Results:Of the 4 patients, 1 patient was males and 3 patients were females; the age was from 4 to 18 years. Nystagmus were seen in 3 cases, finger pressing eyes and night blindness was seen in 1 cases; electroretinogram showed 4 cases of extinction or near extinction. The foveal reflection was visible in all eyes, and there was no obvious abnormality in the peripheral retina. One eye had strong reflection signal with raised ellipsoid in macular area; two eyes had weak reflection signal faintly visible between retinal layers; 1 eye had increased blood vessel branches, peripheral retinal non-perfusion area with capillary leakage; annular strong autofluorescence in macular area 4 eyes. No obvious abnormality was found in the phenotypes of family members. Genetic testing showed that the proband of pedigree 1 (Ⅱ-1) was found a homozygous missense mutation in c.640A>T (p.C214S) (M1) of PRPH2 gene. The proband of pedigree 2 (Ⅱ-2) was found compound heterozygous mutation in c.1256G>A(p.R419Q) (M2) and c.1A>C (p.M1L) (M3) of TULP1 gene. The proband 3 (Ⅱ-1) and her sister (Ⅱ-2) were both found compound heterozygous mutation in c.1943T>C (p.L648P) (M4) and c.380C>T (p.P127L) (M5) of GUCY2D gene. The parents and sister (Ⅱ-1) of the proband in family 2 and the parents of the proband in family 3 were all carriers of the corresponding heterozygous variant. M1, M3, M4, M5 were novel mutations and unreported. The genotype and disease phenotype were co-segregated within the family. According to the analysis of pedigree and genetic testing results, all 3 families were autosomal recessive inheritance. The amino acid conservation analysis found that M1, M2, M3, M4, and M5 were highly conserved among species. The results of bioinformatics analysis were all pathogenic variants. Conclusions:PRPH2 gene M1, TULP1 gene M3, and GUCY2D gene M4, M5 were novel mutations and not been reported in the literature and database. This research expanded the gene mutation spectrum of LCA. The patients with LCA have available characterristics, including onset age, varying ocular fundus and severe visual impairment.

Objective:To understand the application status of rectal drip therapy, so as to make recommendations for its rational application.Methods:In order to analyze the actual situation of rectal drip therapy and the cognition status of the safety, absorption degree and convenience of rectal drip therapy, a questionnaire survey was conducted from 947 different medical institutions in 22 provinces, 4 direct-controlled municipalities and 4 autonomous regions from July 4 to July 15, 2019.Results:(1) A total of 1 505 valid questionnaires were collected from 947 medical institutions in China, 95 medical institutions indicated that 156 drugs were administered by rectal drip, including 35 drugs in tertiary medical institutions, 50 drugs in secondary medical institutions, 67 drugs in primary medical institutions, and 4 drugs in profit medical institutions.(2) The proportion of oral preparations that was used in rectal drip, and in tertiary and secondary medical institutions were 68.57%(24 cases) and 62.00%(31 cases), respectively, both of which was higher than that proportion in primary medical institutions (13 cases, 19.40%). The proportion of injections in primary medical institutions was 80.60%(54 cases) that was higher than that of tertiary medical institutions (11 cases, 31.43%) and secon-dary medical institutions (19 cases, 38.00%), and the differences were statistically significant (all P<0.001). (3) The proportion of digestive system medication rectal dripping in tertiary medical institutions (13 cases, 37.14%) and secondary medical institutions (20 cases, 38.46%) was higher than that in primary medical institutions (3 cases, 4.41%), and the difference was statistically significant ( P<0.001). The proportion of rectal dripping of Traditional Chinese Medicine (TCM) injections in primary medical institutions (47 cases, 69.12%) was higher than that in tertiary medical institutions (1 cases, 2.86%) and secondary medical institutions (0, 0), and the difference was statistically significant ( P<0.001). (4) Among the results of 1 505 questionnaires, 18.61%(280 questionnaire) of doctors thought that rectal drip therapy was safe, 39.34%(592 questionnaire) agreed it was easy to absorb, and 37.34%(562 questionnaire) hold the view that it was convenient.(5) The number of questionnaires in the two groups of used (group A) and not used (group B) was 100 and 1 405, respectively.The cognitive differences in the safety, absorption degree and convenience of rectal drip therapy between the two groups were statistically significant (all P<0.001). Conclusion:There are various drugs used in rectal drip therapy, so it should be strengthened in the management and standardized in pediatrics.

Objective:To understand the hearing loss status of workers exposed to noise, and provide a scientific basis for formulating effective prevention and control strategies.Methods:From Januaryl to October 31 , 2018, through the occupational hazard declaration and record management system of the workplace and the health checkup system , the basic information and physical examination information of 7806 noise-exposed workers in 136 companies in Zhuzhou City in 2018 and the related information about the industry, type, and scale of the enterprises were collected. The χ 2 test was used to analyze the occupational health monitoring data of the noise-exposed workers. Results:The average age of 7806 workers in Zhuzhou was(36. 1±9. 3) years, and the working age was 7. 0(3. 0, 11. 0) years. And 1 270 workers with noise induced hearing loss(NIHL) were detected, including 51 suspected occupational noise deafness. The detection rates of NIHL and the suspected occupational noise deafness were 16. 27% , 0. 65% , respectively. The detection rate of noise was 0.01% in 1deaf person. It showed that the male had higher morbidity than the female ( P<0. 05) and the workers with longer exposure time had a higher morbidity ( P<0. 05) . There was a statistically significant difference in the detection rate of NIHL and suspected occupational noise deafness between workers of different types of work ( P<0. 05 ) . It was noted that the morbidity varied in different enterprises, industry types and terms of scales ( P<0. 05 ) . Non- metal ore mining and dressing industry workers had higher NIHL detection rate (33. 33%, 14/42) and small companies workers had higher NIHL detection rate(19. 32%, 296/1532) . There was a statistically significant difference in the detection rate of suspected occupational noise deafness between workers of different economic types of enterprises. There was a high detection rate of suspected occupational noise deafness among workers in private enterprises(1. 29%, 36/2782) . Conclusion:The noise operation in Zhuzhou is seriously endangered.Occupational health protection measures for non-metallic mining and dressing industries, small and private enterprises should be strengthened.Occupational health law enforcement efforts should be strengthened to protect workers' health.