This study aims to integrate data mining techniques of single cell transcriptomics and spatial transcriptomics, along with animal experiment validation, so as to systematically characterize the protective effects of Jianpi Tongluo Formula(JTF) on the cartilage in knee osteoarthritis(KOA) and elucidate the underlying molecular mechanisms. Single cell transcriptomics and spatial transcriptomics datasets(GSE254844 and GSE255460) of the cartilage tissue obtained from KOA patients were analyzed to map the single cell-spatial heterogeneity and identify key pathogenic factors. After that, a KOA rat model was established via knee joint injection of papain. The intervention effects of JTF on the expression features of these key factors were assessed through real-time quantitative polymerase chain reaction(PCR), Western blot, and immunohistochemical staining. As a result, the integrated single cell and spatial transcriptomics data identified distinct cell subsets with different pathological changes in different regions of the inflamed cartilage tissue in KOA, and their differentiation trajectories were closely related to the inflammatory fibrosis-like pathological changes of chondrocytes. Accordingly, the expression levels of the two key effect targets, namely nuclear receptor coactivator 4(NCOA4) and high mobility group box 1(HMGB1) were significantly reduced in the articular surface and superficial zone of the inflamed joints when JTF effectively alleviated various pathological changes in KOA rats, thus reversing the abnormal chondrocyte autophagy level, relieving the inflammatory responses and fibrosis-like pathological changes, and promoting the repair of chondrocyte function. Collectively, this study revealed the heterogeneous characteristics and dynamic changes of inflamed cartilage tissue in different regions and different cell subsets in KOA patients. It is worth noting that NCOA4 and HMGB1 were crucial in regulating chondrocyte autophagy and inflammatory reaction, while JTF could reverse the regulation of NCOA4 and HMGB1 and correct the abnormal molecular signal axis in the target cells of the inflamed joints. The research can provide a new research idea and scientific basis for developing a personalized therapeutic schedule targeting the spatiotemporal heterogeneity characteristics of KOA.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Osteoarthritis, Knee/pathology* ; Humans ; Male ; Cartilage, Articular/metabolism* ; Chondrocytes/metabolism* ; Rats, Sprague-Dawley ; Female ; Protective Agents/administration & dosage* ; Single-Cell Analysis ; Middle Aged ; HMGB1 Protein/metabolism*

Aromatic traditional Chinese medicine(TCM) has played an important role against epidemics and viruses, and volatile components are the main components that exert the pharmacological effects of aromatic TCM. By screening the related monomer components in aromatic TCM against epidemic and viruses and analyzing and endowing TCM with medicinal properties based on its clinical application and pharmacological research according to the theoretical thinking of TCM, the key technical issues of compatibility of TCM monomer components were solved from a theoretical perspective, providing new ideas and methods for screening raw materials and formulas for the development of new TCM drugs. Based on the conditions of antiviral activity, clinical application foundation, definite therapeutic effect, and high safety, a gradient screening of aromatic TCM was carried out. Firstly, 30 aromatic TCM were screened from anti-epidemic literature and clinical trial formulas, and seven volatile monomers were further screened from them. Then, four monomer components with significant effects, namely patchouli alcohol, carvacrol, p-cymene, and eucalyptol were screened. By adopting the "four-step method for a systematic study of TCM properties", the four monomer components were endowed with medicinal properties, and compatibility and combination studies were conducted to explore the theoretical basis of monomer formulas and form monomer formulas guided by TCM theory. The screening results of volatile monomers in aromatic TCM against viral pneumonia included patchouli alcohol, carvacrol, p-cymene, and eucalyptol. The medicinal properties and compatibility theory of volatile monomer components in TCM were explored. Patchouli alcohol was the main herb, with a cool and pungent nature. It entered the lung meridian to dispel evil Qi and has the effects of aromatization, detoxification, and epidemic prevention. Carvacrol was a minister drug with a cool and pungent taste. It had the effects of aromatizing, moistening, and dissolving the exterior, as well as strengthening the spleen and stomach. p-Cymene was an adjunctive medicine with a mild and pungent nature. It entered the lungs and kidneys and had the effects of aromatic purification, cough relief, and asthma relief. Eucalyptol was also an adjunctive medicine with a pungent and warm taste. It had the functions of aromatic purification, cough relief, phlegm reduction, and pain relief. The combination of the four medicines had the effects of aromatizing, moistening, detoxifying, and epidemic prevention, as well as relieving cough and asthma and strengthening the spleen and stomach. They were used to treat viral pneumonia caused by upper respiratory tract viral infections, with symptoms such as chest tightness, cough, wheezing, fatigue, nasal congestion, runny nose, nausea, and vomiting. This study has laid a literature and theoretical foundation for further drug efficacy verification experiments, compatibility efficacy experiments, and subsequent product development and clinical applications, and it serves as an innovative practice that combines literature research, theoretical research, experimental research, and clinical practice to develop new products.
Drugs, Chinese Herbal/therapeutic use* ; Antiviral Agents/pharmacology* ; Humans ; Pneumonia, Viral/virology* ; Medicine, Chinese Traditional ; Volatile Organic Compounds/pharmacology* ; Animals

This paper aims to investigate the influence of eucalyptol on the biological effects of spleen cold and spleen heat syndromes in rats and its regulation of transient receptor potential vanilloid 1(TRPV1), transient receptor potential melastatin 8(TRPM8), and uncoupling protein 1(UCP1), so as to explore the cold-heat properties of eucalyptol. Rats were randomly divided into groups as follows: blank group, spleen cold syndrome model group, spleen cold syndrome+Atractylodis Rhizoma group, spleen cold syndrome + low-dose eucalyptol group, and spleen cold syndrome+high-dose eucalyptol group, as well as blank group, spleen heat syndrome model group, spleen heat syndrome+Coptidis Rhizoma group, spleen heat syndrome + low-dose eucalyptol group, and spleen heat syndrome + high-dose eucalyptol group. Spleen cold and spleen heat syndromes were induced by disorders of hunger and satiety combined with bitter cold drugs, as well as a high-fat diet combined with liquor. Except for the blank and model groups, the other groups were administered once a day during the modeling process for 14 consecutive days. The general condition and body weight of rats in each group were observed, and the histopathological morphology of the gastric antrum and small intestine was observed by hematoxylin-eosin(HE) staining. The contents of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), Na~+-K~+-ATPase, total cholesterol(TC), triglyceride(TG), gastrin(GAS), motilin(MTL), D-xylose, and other related indices were detected in rats. The expression levels of TRPV1, TRPM8, and UCP1 in small intestine tissue of rats with spleen cold syndrome were detected. The results showed that eucalyptol had a certain degree of improvement in the overall state and body weight of rats with spleen cold syndrome. Compared with the spleen cold syndrome model group, high-dose eucalyptol significantly increased the levels of serum cAMP, cAMP/cGMP, TG, and TC in rats with spleen cold syndrome(P<0.05, P<0.01), decreased the content of cGMP, and significantly elevated the levels of gastrointestinal function-related indicators GAS, MTL, and D-xylose(P<0.05, P<0.01). Low-dose eucalyptol significantly increased the level of cAMP/cGMP in the serum and Na~+-K~+-ATPase levels in hepatic tissue(P<0.05, P<0.01), and significantly increased the levels of GAS and D-xylose(P<0.01). Eucalyptol showed similar effects to Atractylodis Rhizoma with a warm nature on rats with spleen cold syndrome. Compared with the spleen heat syndrome model group, the high-dose and low-dose eucalyptol groups showed a trend of increase in gastrointestinal indicators, with no significant changes in other indicators. In addition, high-dose eucalyptol increased the expression of TRPV1 and UCP1 and decreased the expression of TRPM8 in the small intestine tissue of rats with spleen cold syndrome. Eucalyptol could affect the cyclic nucleotide and material energy metabolism levels of rats with spleen cold syndrome and had a certain improvement effect on their gastrointestinal digestion and absorption function, thereby improving spleen cold syndrome. Eucalyptol had no significant improvement effect on rats with spleen heat syndrome, suggesting that eucalyptol may have a warm nature and regulate spleen meridians. It is speculated that eucalyptol may exhibit its medicinal properties by activating the TRPV1 pathway, promoting the expression of UCP1, and inhibiting the TRPM8 channel.
Animals ; Rats ; Spleen/metabolism* ; Male ; TRPV Cation Channels/genetics* ; Rats, Sprague-Dawley ; Eucalyptol/administration & dosage* ; TRPM Cation Channels/genetics* ; Uncoupling Protein 1/genetics* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Cold Temperature ; Cyclic GMP/metabolism*

This paper aims to study the effect of p-cymene on mice with deficiency-cold syndrome induced by hydrocortisone and deficiency-heat syndrome induced by dexamethasone and explore the medicinal properties and mechanism of p-cymene with mild and warm nature based on the dominant characteristics of the two-way applicable conditions of mild drugs. A total of 80 KM mice were randomly divided into blank group, deficiency-cold syndrome model group, deficiency-cold syndrome + ginseng group, and deficiency-cold syndrome + low-dose and high-dose p-cymene groups, as well as blank group, deficiency-heat syndrome model group, deficiency-heat syndrome + American ginseng group, and deficiency-heat syndrome + low-dose and high-dose p-cymene groups. Hydrocortisone and dexamethasone solution were intragastrically administered for 14 consecutive days to prepare deficiency-cold syndrome and deficiency-heat syndrome models. Except for the blank group and the model group intragastrically administered with normal saline, the other groups were intragastrically administrated with drugs for 14 days. The levels of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), total cholesterol(TC), triglyceride(TG), immunoglobin G(IgG), and immunoglobin M(IgM) in serum, as well as the activity of Na~+-K~+-ATPase in liver tissue were detected. The expression of transient receptor potential melastatin 8(TRPM8), transient receptor potential vanilloid 1(TRPV1), and uncoupling protein 1(UCP1) in brown adipose tissue of deficiency-cold syndrome model after intervention with p-cymene was studied. The results showed that p-cymene could effectively improve the levels of cAMP, cAMP/cGMP, TC, IgM, and IgG in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and reduce the content of cGMP. The effects on T3, T4, and TG were not statistically significant. At the same time, p-cymene could reduce the levels of cAMP, cAMP/cGMP, and T4 in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and increase the levels of cGMP, IgM, and IgG, and it had no effect on T3, TC, and TG. In addition, p-cymene could up-regulate the expression of TRPV1 and UCP1 in brown fat of mice with deficiency-cold syndrome and down-regulate the expression of TRPM8. In summary, p-cymene could significantly regulate the syndrome indexes of mice with deficiency-cold syndrome, and some indexes of mice with deficiency-heat syndrome could be improved, but the effects on lipid metabolism and energy metabolism indexes were not obvious, indicating that the regulation effect of p-cymene on deficiency-cold syndrome model was more prominent and that the medicinal properties of p-cymene were mild and warm. The regulation of TRPV1/TRPM8/UCP1 channel expression may be the molecular biological mechanism of p-cymene with mild and warm nature affecting the energy metabolism of the body.
Animals ; Cymenes ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Disease Models, Animal ; Humans ; Cyclic AMP/metabolism* ; Monoterpenes/administration & dosage* ; Liver/metabolism* ; Cyclic GMP/metabolism* ; TRPV Cation Channels/genetics* ; Uncoupling Protein 1/genetics*

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

Objective:To summarize the best evidence on case management of patients with home enteral nutrition.Methods:Relevant evidence on the case management of home enteral nutrition patients was retrieved by literature search,and the evidence was extracted and summarized for the literature that met the quality requirements.Result:A total of 10 literatures were included,including 1 guideline,3 expert consensus,2 industry standards,1 systematic review and 3 randomized controlled trials.By establishment of archives,policy management,establishment of multidisciplinary teams,overall evaluation of home enteral nutrition,as well as implementation management,a total of 33 home enteral nutrition case management was summarized from 6 aspects including health education and follow-up,etc.Conclusion:All the summarized relevant evidence about case filing and management of home enteral nutrition patients can be applied in clinical practice to promote the standardized management of home enteral nutrition.

The experience of professor YANG Wen-Hui in treating lumbago disease with YANG's Baliao-acupoints moxibustion is introduced in this paper.YANG Wen-Hui believes that the basic pathogenesis of lumbago disease is'cold causes lower back pain',and based on the philosophical idea of'harmony in Shushu(the ways to cultivate health)',he proposes'YANG's Baliao-acupoints moxibustion'for the treatment of lumbago disease.According to the patient's condition,professor YANG used the acupoints of Shangliao(BL31),Ciliao(BL32),Zhongliao(BL33),and selected the moxa cone like jujube core,soybean or wheat grain,and applied moxibustion with the technique of'San Yang Kai Tai'or'Ruo feng Chui Yun',the number of moxibustion is proportional to the age of the patient.YANG's Baliao-acupoints moxibustion in treating lumbago disease exerts highly and remarkable clinical efficacy,and it was widely acclaimed by the patients.

AIM To investigate the influencing factors in scale-up of extraction process for Yunpi Xiaoshi Prescription.METHODS HPLC was adopted in the content determination of catechin,ferulic acid,taxifolin,isovitexin,narirutin,atractylenolideⅡ,naringin,morin,hesperidin,luteolin,hederagenin,atractylenolideⅠ,naringenin and hesperetin,the fingerprints were established,after which the effects of container volume,optimal fire and feeding quantity on the contents of various constituents were evaluated.RESULTS Fifteen batches of samples demonstrated the similarities of more than 0.995.Fourteen constituents showed good linear relationships within their own ranges(r>0.999 0),whose average recoveries were 96.4%-103.3%with the RSDs of 0.5%-2.7%.The influencing degree of optimal fire was greater than that of container volume and feeding quantity.CONCLUSION The combination of multi-component content determination and fingerprints can provide data basis and theoretical reference for the technology of consistency evaluation in scale-up of extraction process for Yunpi Xiaoshi Prescription.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]