Adverse Side Effects of COVID-19 Vaccines in Older Adults: A Comprehensive Review of Current Research

The purpose of this research review was to examine current scientific literature on COVID-19 vaccine-induced side effects in older adults. We reviewed studies focusing on side effects categorized into cardiologic, immunologic, neurologic, and ocular groups. Cardiologic side effects included myocarditis, pericarditis, and myocardial infarction. Immunologic conditions examined were anaphylaxis and vaccine-induced immune thrombotic thrombocytopenia. Neurologic side effects included Guillain-Barré syndrome and Bell’s Palsy. Ocular side effects covered ocular swelling, submacular hemorrhage, and corneal graft rejection after keratoplasty and Descemet membrane endothelial keratoplasty. Additionally, less common side effects in older adults were reviewed but found to be statistically rare. Overall, COVID-19 vaccine-induced side effects in elderly populations were rare. We concluded that the vaccine’s efficacy in preventing excess deaths due to COVID-19 is significant, and the risk of these rare side effects does not justify foregoing vaccination in at-risk individuals. Patients at higher risk for these side effects should be informed, and additional considerations should be made by their treating physician. This review aims to increase awareness of rare vaccine-induced side effects to encourage further studies, enhancing understanding of their etiology and prevalence in at-risk older adult populations.

Studying the co-evolution of information diffusion,vaccination behavior and disease transmission in multilayer networks with local and global effects

Today,with the rapid development of the internet,a large amount of information often accompanies the rapid transmission of disease outbreaks,and increasing numbers of scholars are studying the relationship between information and the disease transmission process using complex networks.In fact,the disease transmission process is very complex.Besides this information,there will often be individual behavioral measures and other factors to consider.Most of the previous research has aimed to establish a two-layer network model to consider the impact of information on the transmission process of disease,rarely divided into information and behavior,respectively.To carry out a more in-depth analysis of the disease transmission process and the intrinsic influencing mechanism,this paper divides information and behavior into two layers and proposes the establishment of a complex network to study the dynamic co-evolution of information diffusion,vaccination behavior,and disease transmission.This is achieved by considering four influential relationships between adjacent layers in multilayer networks.In the information layer,the diffusion process of negative information is described,and the feedback effects of local and global vaccination are considered.In the behavioral layer,an individual's vaccination behavior is described,and the probability of an individual receiving a vaccination is influenced by two factors:the influence of negative information,and the influence of local and global disease severity.In the disease layer,individual susceptibility is considered to be influenced by vaccination behavior.The state transition equations are derived using the micro Markov chain approach(MMCA),and disease prevalence thresholds are obtained.It is demonstrated through simulation experiments that the negative information diffusion is less influenced by local vaccination behavior,and is mainly influenced by global vaccination behavior;vaccination behavior is mainly influenced by local disease conditions,and is less influenced by global disease conditions;the disease transmission threshold increases with the increasing vaccination rate;and the scale of disease transmission increases with the increasing negative information diffusion rate and decreases with the increasing vaccination rate.Finally,it is found that when individual vaccination behavior considers both the influence of negative information and disease,it can increase the disease transmission threshold and reduce the scale of disease transmission.Therefore,we should resist the diffusion of negative information,increase vaccination proportions,and take appropriate protective measures in time.

Adverse Events following AstraZeneca COVID-19 Vaccination: A Case Study in Abidjan, Côte d’Ivoire

Introduction: Pharmaceutical companies have boosted vaccine production following the global COVID-19 pandemic. In Côte d’Ivoire, the first vaccination campaign with the AstraZeneca vaccine began on March 1, 2021, as part of the Covax program. Despite the positive benefit/risk balance, the adverse effects of vaccination should not be minimized. Objective: To identify adverse events of AstraZeneca’s COVID-19 vaccination for better management. Materials and Methods: This is a case of a 57-year-old obese (BMI = 39 kg/m2) female health care worker who experienced adverse events in March 2021 after the second dose of AstraZeneca vaccine administered 4 weeks apart. These were subject to mandatory case reporting. Results: Major post-vaccination events occurred in a noisy systemic picture with parameters showing significant disturbances. Biological surveillance remains costly and makes the accountability of the vaccine complex. Conclusion: Vaccination remains the ultimate weapon in the fight against endemic diseases but should not overshadow the reporting of adverse events.

Adverse Effects of Inactivated Foot-and-Mouth Disease Vaccine—Possible Causes Analysis and Countermeasures

Foot-and-mouth disease (FMD) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, and Chinese government adopts compulsory immunization measures for FMD. The adverse effects of FMD vaccine to pigs, cattle and goats have been reported increasingly frequent during the spring and autumn seasons when large numbers of farm livestock are vaccinated. The financial losses caused by vaccine adverse effects have been a serious concern for both farmers and primary prevention personnel. There are various causative factors reported to involve into adverse effect of FMD vaccine, including the inappropriate vaccine production, transportation and storage, livestock poor tolerance, and unqualified vaccinating manipulations. Symptomatic treatment and early drug prevention have a certain effect on the adverse effects. To analyze causes and propose countermeasures, in the current study possible reasons during the production and processing procedures of inactivated FMD vaccine were reviewed and corresponding countermeasures were recommended. The review may provide references for better use of vaccine to prevent FMD.

Long-lasting discussion: Adverse effects of intraoperative blood loss and allogeneic transfusion on prognosis of patients with gastric cancer

Gastrectomy with radical lymph node dissection is the most promising treatment avenue for patients with gastric cancer. However, this procedure sometimes induces excessive intraoperative blood loss and requires perioperative allogeneic blood transfusion. There are lasting discussions and controversies about whether intraoperative blood loss or perioperative blood transfusion has adverse effects on the prognosis in patients with gastric cancer. We reviewed laboratory and clinical evidence of these associations in patients with gastric cancer. A large amount of clinical evidence supports the correlation between excessive intraoperative blood loss and adverse effects on the prognosis. The laboratory evidence revealed three possible causes of such adverse effects: anti-tumor immunosuppression, unfavorable postoperative conditions, and peritoneal recurrence by spillage of cancer cells into the pelvis. Several systematic reviews and meta-analyses have suggested the adverse effects of perioperative blood transfusions on prognostic parameters such as all-cause mortality, recurrence, and postoperative complications. There are two possible causes of adverse effects of blood transfusions on the prognosis: Anti-tumor immunosuppression and patient-related confounding factors (e.g., preoperative anemia). These factors are associated with a worse prognosis and higher requirement for perioperative blood transfusions. Surgeons should make efforts to minimize intraoperative blood loss and transfusions during gastric cancer surgery to improve patients’ prognosis.

Prevention and Nursing of Adverse Reactions of Novel Coronavirus Inactivated Vaccine (Vero Cells)

Objective:To discuss and analyze the causes of adverse reactions caused by the inactivated novel coronavirus vaccine(Vero cells),and to propose methods of prevention and care.Methods:A questionnaire was used to randomly select 229 adults who were vaccinated with the inactivated novel coronavirus vaccine(Vero cells)at Xi’an People’s Hospital(Xi’an Fourth Hospital).The adverse reactions were statistically analyzed.Results:Among the 229 adults vaccinated with the inactivated novel coronavirus vaccine(Vero cells),30 experienced vaccination reactions.The main reaction was local induration at the inoculation site,and dizziness was the primary systemic symptom.Conclusion:To reduce the incidence of adverse reactions to the inactivated novel coronavirus vaccine(Vero cells),it is necessary to effectively evaluate the health status of adults before vaccination,select the correct vaccination site,and strictly implement the rules of 3-inspections,7-checks,and 1-verification.Standardizing the operation process and providing thorough health education after vaccination can effectively reduce the occurrence of adverse reactions.

Adverse effects of oral antiviral therapy in chronic hepatitis B

Oral nucleoside/nucleotide analogues(NAs) are currently the backbone of chronic hepatitis B(CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects(i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a "Black Box" warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus(HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment.

Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases

The outbreak of coronavirus disease 2019(COVID-19)is a global pandemic.Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality.The drugs of higher interest include umifenovir,bromhexine,remdesivir,lopinavir/ritonavir,steroid,tocilizumab,interferon alpha or beta,ribavirin,fivapiravir,nitazoxanide,ivermectin,molnupiravir,hydroxychloroquine/chloroquine alone or in combination with azithromycin,and baricitinib.Gastrointestinal(GI)symptoms and liver dysfunction are frequently seen in patients with COVID-19,which can make it difficult to differentiate disease manifestations from treatment adverse effects.GI symptoms of COVID-19 include anorexia,dyspepsia,nausea,vomiting,diarrhea and abdominal pain.Liver injury can be a result of systemic inflammation or cytokine storm,or due to the adverse drug effects in patients who have been receiving different treatments.Regular monitoring of liver function should be performed.COVID-19 vaccines have been rapidly developed with different technologies including mRNA,viral vectors,inactivated viruses,recombinant DNA,protein subunits and live attenuated viruses.Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks.Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.

Intravesical bacillus Calmette-Guerin(BCG)in treating non-muscle invasive bladder cancer—analysis of adverse effects and effectiveness of two strains of BCG(Danish 1331 and Moscow-I)

Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.

Nursing of adverse effects in patients treated with liver resection plus sorafenib for hepatocellular carcinoma:5 cases report

There were very few reports of adverse effects in patients treated by liver resection in combination with sorafenib. We present 5 cases of hepatocellular carcinoma treated with liver resection plus sorafenib, trying to observing the adverse effects and seeking the nursing options to the adverse effects. The 5 patients were all males, and the mean age was （38.6-a：13.4） years. Tumor sizes were （6.7＋2.2） cm, and liver function was Child-Pugh class A. Diagnosis of Hepatocellular carcinoma （HCC） was confwmed by postoperative pathology. During the follow-ups, all the 5 patients had different degrees of adverse effects, of which 5 patients had diarrhea, 3 had hand-foot skin reaction, 1 had hypertension and 1 had alopecie. Diarrhea seems common in these patients, and it appeared early after treatment. For those patients with adverse effects, management measures were given immediately, including nursing interventions and some medicines. Psychological and symptomatic nursing guidance can help patients overcome the adverse effects. No patients suffered dose reduction or treatment discontinuation.

Efficacy and adverse effects of olanzapine in the treatment of moderate to severe refractory neuropathic pain

Objective The aim of the study was to investigate the efficacy and adverse effects of olanzapine in the treatment of moderate to severe refractory neuropathic pain.Methods Forty patients with digestive system cancer were enrolled,who had moderate to severe refractory neuropathic pain;the patients were treated with olanzapine for 2 weeks at a daily dosage of 5 mg to 10 mg per night according to patients’response and tolerability,combined with conventional analgesic therapy.Pain intensity was evaluated by using a Numeral Rating Scale(NRS)at baseline,3 days,and 2 weeks after therapy.The Pittsburg Sleep Quality Index(PSQI)was evaluated at baseline and 2 weeks after therapy.Data on adverse events were recorded.The dosage of conventional analgesics was adjusted over time based on the severity of pain.Results The mean pain score decreased by 2.575±1.318(P<0.000)at 3 days and by 3.400±1.614(P<0.000)at 2 weeks;30%of the patients experienced significant pain relief at 3 days and 50%at 2 weeks.The PSQI decreased by 4.725±2.828(P<0.000)at 2 weeks.The adverse events induced by olanzapine included sleepiness,weight gain,dizziness,fatigue,dry mouth,and constipation;all the side effects were mild.Conclusion When combined with conventional analgesic therapy,olanzapine was effective in relieving pain and sleep disturbance,and was well-tolerated among patients with refractory neuropathic pain.

Pain reduction and adverse effects of intravenous metoclopramide for acute migraine attack: A systematic review and meta-analysis of randomized-controlled trials

BACKGROUND Metoclopramide may be used to treat people suffering from acute migraine.However,no comprehensive investigation on this issue has been recorded.This review will provide more solid evidence for the use of metoclopramide in treating acute migraine.AIM To compare the efficacy of intravenous metoclopramide with other therapies in migraine attack treatment in an emergency department(ED).METHODS We included randomized controlled trials of participants older than 18 years with acute migraine headaches,which included at least one arm that received intravenous(IV)metoclopramide at the ED.A literature search of PubMed,Web of Science,Cochrane Collaboration,and Reference Citation Analysis on December 31,2021 retrieved other drugs or placebo-controlled studies without language limitation.The risk of bias was assessed using the Cochrane risk of bias tool.The primary endpoint was pain reduction at 60 min or closest to 1 h after treatment,as measured by the pain scale.Secondary endpoints included adverse effects or reactions resulting from metoclopramide or comparisons.RESULTS Fourteen trials with a total of 1661 individuals were eligible for review.The risk of bias ranged from low to intermediate.IV metoclopramide administration was not associated with higher pain reduction at 1 h(Standard mean difference[SMD]=-0.03,95%confidence interval[CI]:-0.33-0.28,P=0.87).However,metoclopramide was associated with better pain reduction than placebo(SMD=1.04,95%CI:0.50-1.58,P=0.0002).In addition,side effects were not significantly different between IV metoclopramide and other drugs or placebo(odds ratio[OR]=0.76,95%CI:0.48-1.19,P=0.09 and OR=0.92,95%CI:0.31-2.74,P=0.54,respectively).CONCLUSION Metoclopramide is more effective than placebo in treating migraine in the ED.Despite the observed tendency of decreased side effects,its effectiveness compared to other regimens is poorly understood.More research on this area is needed to treat migraine in acute care settings effectively.

Effectiveness and adverse effects of hormonal therapy for prostate cancer： Japanese experience and perspective

Recently, novel anti-androgens and inhibitors of androgen biosynthesis have been developed through the elucidation of mechanisms of castration resistance of prostate cancer. We believe that these new developments will improve hormonal therapy. On the other hand, there has been an increase in criticism of hormonal therapy, because hormonal therapy is supposed to induce adverse effects such as cardiovascular disease. In this review, we have introduced the Japanese experience of hormonal therapy, because we believe that there may be ethnic differences between Caucasians and Asian people in the efficacy and adverse effects of hormonal therapy. First, we showed that primary hormonal therapy can achieve long-term control of localized prostate cancer in some cases and that quality of life of patients receiving hormonal therapy is rather better than previously thought. Neoadjuvant and adjuvant hormonal therapy in cases undergoing radical prostatectomy or radiotherapy are very useful for high-risk or locally advanced prostate cancer. Further clinical trials are required to confirm the efficacy of neoadjuvant or adjuvant hormonal therapy. We showed that the death from cardiovascular dis- eases in Japanese patients receiving hormonal therapy was not higher than that in the general population. However; efforts should be made to decrease the adverse effects of hormonal therapy, because life-style change may increase the susceptibility to adverse effects by hormonal therapy even in Japan. Managements of endocrine and metabolic dysfunction, such as diabetes mellitus, are essential. New hormonal compounds such as selective androgen receptor modulators capable of specifically targeting prostate cancer are expected to be developed.

A Case of Adverse Reaction to Booster Dose of COVID-19 Vaccination: Could D-Dimer Elevation Suggest Increased Clotting Risk?

We report the clinical case of a 40-year-old Italian woman, who soon after her booster vaccination with mRNA-1273 after the two previous vaccinations with BNT162b2, developed severe headache, high fever, and Musculo-skeletal pain. She went to the emergency department, where computerized tomography (CT) scans of chest and brain were performed, resulting in both negative for pathologic findings. On the contrary, white blood count was strongly lowered and D-dimer severely elevated. She improved after treatment with enoxaparin and the blood analyses returned in the normal range after ten days. This case supports the hypothesis that COVID-19 vaccines could increase blood clotting in some predisposed subjects. Therefore, we believe that robust and well-designed clinical trials, considering the evaluation of D-dimer levels, should be performed to eliminate any doubts on this issue.

Does Low-Dose Intravenous Methylprednisolone Pulse Therapy Produce Unacceptable Adverse Effects in Children?

Background: Intravenous methylprednisolone pulse therapy has been used since the late 1960s for acute transplant rejection or severe renal involvement in systemic lupus erythematosus and primary glomerulonephritis. However, reports of serious adverse effects such as life-threatening cardiac arrhythmias and sudden death raise questions about its safety. Objective: To investigate the incidence of significant adverse effects associated with low-dose methylprednisolone pulse therapy (LDMPT) in pediatric patients. Methods: We retrospectively analyzed adverse effects during and after LDMPT in 68 patients (median age: 11.4 years;43% male) with various glomerular diseases who were admitted to Saitama Children’s Medical Center between April 2007 and December 2010. LDMPT consisted of pulse methylprednisolone (15-20 mg/kg;maximum 600 mg/d) for 3 consecutive days weekly for 2-3 weeks. Results: Although adverse effects occurred in 54 of 68 patients (79%), most were mild and transient. Transient glycosuria was noted in 46 patients (68%), hypertension in 6 (9%), elevated intraocular pressure in 6 (9%), hypokalemia in 5 (7%), and liver damage in 2 (3%). No late-onset adverse effects such as osteoporotic fractures, steroid diabetes mellitus, or short stature were observed. Conclusion: LDMPT appears to be relatively safe and well tolerated in children with various glomerular diseases.

Prevention and management of adverse events following COVID-19 vaccination using traditional Korean medicine:An online survey of public health doctors

BACKGROUND Since February 2021,vaccination against coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 has started in Korea.AIM To perform a questionnaire survey about the prevention and management of adverse events of COVID-19 vaccination among public health doctors of Korean Medicine(PHKMDs).METHODS An online questionnaire was developed,comprising categories about adverse events of vaccination(AEVs)and perception of using Korean medicine(KM)in managing vaccine adverse events(AEs)among PHKMDs.PHKMDs’experience of AEVs,usage of Korean medicine for AEVs,and perception and attitude in using KM for AEVs were surveyed.The survey web-link was emailed to the association of PHKMDs.Online links were sent through Survey Monkey to all PHKMDs in Korea.RESULTS A total of 143 participants were recruited for this study;65%of participants were vaccinated at the same of the survey(n=93).Although most participants did not take any medication for prevention of the adverse events,62%(n=58)of participants had taken herbal medicine to treat the adverse events(n=52).Approximately 35%of participants(n=33)said that they would recommend taking herbal medicine to prevent any AEVs.From various KM interventions,the participants strongly recommended taking an herbal medicine(n=69,74.19%)to treat AEs,and the second-highest was acupuncture treatment(n=19,20.43%).CONCLUSION Overall,this research demonstrated a high prevalence of KM usage by the PHKMDs.Hence,this study’s results may serve as fundamental evidence for health professionals to consider using KM treatments when treating or preventing AEVs in the near future.

Modeling and simulation of induction motor drive system to investigate and mitigate of PWM inverter’s adverse effects

Modeling and simulation of induction motor drive system to investigate and mitigate the adverse effects of PWM inverter based on analysis, modeling and simulation are presented. The estimation of conducted disturbances and other adverse effects of PWM inverter by simulation offer a considerable gain from the economic point of view. For an accurate model of the motor drive system including mains, rectifier, inverter, motor and its long cables, the high frequency parasitic current paths are taken into account. The novel model and its parasitic values for three-phase induction motor system are presented. Finally a new solution for suppressing EMI, common mode voltage, leakage current, bearing current and shaft voltages is proposed and the results show the excellent performances of proposed solution including active and passive filters.

Assessing Adverse Effects of Aroclor 1254 on Perinatally Exposed Rat Offspring

To assess the neurotoxic effects and redoxresponses of Aroclor 1254 （A1254） on perinatallyexposed rat offspring, A1254 was administered bygavage from gestational day （GD） 6 to postnatal day（PND） 21. Neurobehavioral development,antioxidant enzyme activities, lipid peroxidation（LPO）, nitric oxide （NO）, and NO synthase （NOS）levels were analyzed in the offspring.Neurobehavioral development analysis revealeddelayed appearance of the righting reflex, negativegeotaxis, and cliff drop test responses in A1254exposed group. Developmental A1254 exposurealso caused oxidative stress in the brain of PND 22offspring via reductions in the activity of SOD andGSH-Px, and by promoting a rise in the levels of NOand NOS.

Systemic adverse effects and toxicities associated with immunotherapy:A review

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers.Immunotherapeutic agents have gained immense popularity due to their tumorspecific action.Immunotherapy is slowly transforming into a separate therapeutic entity,and the fifth pillar of management for cancers alongside surgery,radiotherapy,chemotherapy,and targeted therapy.However,like any therapeutic entity it has its own adverse effects.With the increasing use of immunotherapeutic agents,it is vital for physicians to acquaint themselves with these adverse effects.The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents.We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems,as well as an extensive discussion of the current recommendations for treatment and clinical trial data.As we continue to see increasing usage of these agents in clinical practice,it is vital for physicians to familiarize themselves with these effects.

Survey about the Adverse effects of Chinese medicine and its preparations

The usefulness of Chinese herbs and natural products as healing agents has been known for thousand years. And a lot of Chinese believe that Chinese traditional medicine is not a category of folk medicine, but a kind of well organized system. In the other hand many western countries refuse to admit the legal position of Chinese traditional medicine as it's not an evidence-based medicine. Even Chinese themselves cannot deny the Adverse effects of Chinese medicine and its preparations. However no one can point out the effect, no mater good or bad, of traditional Chinese medicine. In this paper, the author surveys this puzzle.